On May 26, 2022 EMD Serono, the healthcare business of Merck KGaA, Darmstadt, Germany, in the US and Canada, reported the latest research representing the Company’s innovative oncology portfolio has been accepted for presentation at this year’s American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 3-7, 2022 (Press release, EMD Serono, MAY 26, 2022, View Source [SID1234615137]). Data encompass Company-sponsored, investigator-sponsored, and external collaboration studies.

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Abstracts to be shared at the meeting include data for the Company’s licensed medicines BAVENCIO (avelumab), TEPMETKO (tepotinib) and its oncology pipeline. The presentations span key tumor types including advanced urothelial carcinoma (UC), advanced renal cell carcinoma (RCC), metastatic non-small cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), and head and neck cancer (SCCHN).

"We look forward to coming together with the scientific community at ASCO (Free ASCO Whitepaper) 2022, where we will share the latest data from our portfolio, which demonstrate our determination to make a real difference in the lives of patients with some of the most challenging cancers," said Victoria Zazulina, Head of Development Unit, Oncology, for the Healthcare business of Merck KGaA, Darmstadt, Germany.

Select presentations include:

BAVENCIO (avelumab): New analyses of long-term data from the Phase III JAVELIN Bladder 100 study of BAVENCIO as first-line maintenance treatment in advanced UC, including data from subgroups defined by best response to first-line chemotherapy and in patients who did or did not receive second-line treatment after BAVENCIO maintenance.
TEPMETKO (tepotinib): Data for the oral MET inhibitor TEPMETKO include two poster presentations from the VISION trial reporting efficacy, safety and quality-of-life results of TEPMETKO in Asian patients with METex14 skipping NSCLC, and updated efficacy and safety results of TEPMETKO and exploratory biomarker analyses in patients with NSCLC with high-level MET amplification enrolled into Cohort B of the VISION trial based on liquid biopsy.
Berzosertib: Results from research collaborations assessing the intravenous ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor berzosertib, including the National Cancer Institute’s (NCI) Cancer Therapy Evaluation Program 9938 Phase I study of berzosertib plus irinotecan in patients with advanced solid tumors and NCI single-arm Phase II data of berzosertib plus topotecan in patients with relapsed extra-pulmonary small cell neuroendocrine carcinomas.
Below is a selection of key Merck KGaA, Darmstadt, Germany-related abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) 2022:

Title

Lead Author

Abstract/#

Session Title/Date/Time

BAVENCIO (avelumab)

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy

BP Valderrama

4559

Genitourinary Cancer—Kidney and Bladder

Saturday, June 4, 2022

1:15 PM-4:15 PM CDT

Long-term outcomes in patients with advanced urothelial carcinoma (UC) who received avelumab first-line (1L) maintenance with or without second-line (2L) treatment: exploratory analyses from JAVELIN Bladder 100

J Bellmunt

4560

Genitourinary Cancer—Kidney and Bladder

Saturday, June 4, 2022

1:15 PM-4:15 PM CDT

TEPTMETKO (tepotinib)

Tepotinib in Asian patients with advanced NSCLC with MET exon 14 (METex14) skipping

T Kato

9120

Lung Cancer—Non-Small Cell Metastatic

Monday, June 6, 2022

8:00 AM-11:00 AM CDT

Clinical response to tepotinib according to circulating tumor (ct) DNA biomarkers in patients with advanced NSCLC with high-level MET amplification (METamp) detected by liquid biopsy (LBx)

X Le

9121

Lung Cancer—Non-Small Cell Metastatic

Monday, June 6, 2022

8:00 AM-11:00 AM CDT

Pipeline

Berzosertib (M6620)*

Targeting genomic instability in extrapulmonary small cell neuroendocrine cancers: a phase II study with ATR inhibitor berzosertib and topotecan

N Takahashi

8518

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Monday, June 6, 2022

Live discussion: 12:26 PM CDT

NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors

LC Villaruz

3012

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sunday, June 5, 2022

Live Discussion: 4:42 PM CDT

*These studies are sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under its Cooperative Research and Development Agreement with Merck KGaA, Darmstadt, Germany for M6620.

Merck KGaA, Darmstadt, Germany is a science-led organization dedicated to delivering transformative medicines with the goal of making a meaningful difference in the lives of people affected by cancer. Our oncology research efforts aim to leverage our synergistic portfolio in oncogenic pathways, immuno-oncology, and DNA Damage Response (DDR) to tackle challenging tumor types in gastrointestinal, genitourinary, and thoracic cancers. Our curiosity drives our pursuit of treatments for even the most complex cancers, as we work to illuminate a path to scientific breakthroughs that transform patient outcomes. Learn more at www.emdseronooncology.com.

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.7-9 In November 2014, Merck KGaA, Darmstadt, Germany and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
BAVENCIO (avelumab) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

BAVENCIO in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

BAVENCIO is currently approved for at least one indication for patients in more than 50 countries.

BAVENCIO Important Safety Information from the US FDA-Approved Label
BAVENCIO can cause severe and fatal immune-mediated adverse reactions in any organ system or tissue and at any time after starting treatment with a PD-1/PD-L1 blocking antibody, including after discontinuation of treatment.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

No dose reduction for BAVENCIO is recommended. For immune-mediated adverse reactions, withhold or permanently discontinue BAVENCIO depending on severity. In general, withhold BAVENCIO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue BAVENCIO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids. In general, if BAVENCIO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic corticosteroids (eg, endocrinopathies and dermatologic reactions) are discussed in subsequent sections.

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4 pneumonitis. Immune-mediated pneumonitis occurred in 1.2% (21/1738) of patients, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (0.3%) and Grade 2 (0.6%) adverse reactions. Systemic corticosteroids were required in all (21/21) patients with pneumonitis.

BAVENCIO can cause immune-mediated colitis. The primary component of immune-mediated colitis consisted of diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 colitis. Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including Grade 3 (0.4%) and Grade 2 (0.7%) adverse reactions. Systemic corticosteroids were required in all (26/26) patients with colitis.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis. Withhold or permanently discontinue BAVENCIO based on tumor involvement of the liver and severity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% (16/1738) of patients, including fatal (0.1%), Grade 3 (0.6%), and Grade 2 (0.1%) adverse reactions. Systemic corticosteroids were required in all (16/16) patients with hepatitis.

BAVENCIO in combination with INLYTA can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation compared to BAVENCIO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold or permanently discontinue both BAVENCIO and INLYTA based on severity of AST, ALT, or total bilirubin elevation, and consider administering corticosteroids as needed. Consider rechallenge with BAVENCIO or INLYTA, or sequential rechallenge with both BAVENCIO and INLYTA, after recovery. In patients treated with BAVENCIO in combination with INLYTA in the advanced RCC trials, increased ALT and increased AST were reported in 9% (Grade 3) and 7% (Grade 4) of patients. Immune-mediated hepatitis was reported in 7% of patients including 4.9% with Grade 3 or 4 immune-mediated hepatitis. Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant.

BAVENCIO can cause primary or secondary immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated adrenal insufficiency occurred in 0.5% (8/1738) of patients, including Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in all (8/8) patients with adrenal insufficiency.

BAVENCIO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated pituitary disorders occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction.

BAVENCIO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism, as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Thyroiditis occurred in 0.2% (4/1738) of patients, including Grade 2 (0.1%) adverse reactions. Hyperthyroidism occurred in 0.4% (7/1738) of patients, including Grade 2 (0.3%) adverse reactions. Systemic corticosteroids were required in 29% (2/7) of patients with hyperthyroidism. Hypothyroidism occurred in 5% (90/1738) of patients, including Grade 3 (0.2%) and Grade 2 (3.7%) adverse reactions. Systemic corticosteroids were required in 7% (6/90) of patients with hypothyroidism.

BAVENCIO can cause immune-mediated type I diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated type I diabetes mellitus occurred in 0.1% (2/1738) of patients, including Grade 3 (0.1%) adverse reactions.

BAVENCIO can cause immune-mediated nephritis with renal dysfunction. Withhold BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for Grade 4 increased blood creatinine. Immune-mediated nephritis with renal dysfunction occurred in 0.1% (1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction. Systemic corticosteroids were required in this patient.

BAVENCIO can cause immune-mediated dermatologic adverse reactions, including rash or dermatitis. Exfoliative dermatitis including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold BAVENCIO for suspected and permanently discontinue for confirmed SJS, TEN, or DRESS. Immune-mediated dermatologic adverse reactions occurred in 5% (90/1738) of patients, including Grade 3 (0.1%) and Grade 2 (2.0%) adverse reactions. Systemic corticosteroids were required in 29% (26/90) of patients with dermatologic adverse reactions.

BAVENCIO can result in other immune-mediated adverse reactions. Other clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in patients who received BAVENCIO or were reported with the use of other PD-1/PD-L1 blocking antibodies. For myocarditis, permanently discontinue BAVENCIO for Grade 2, Grade 3, or Grade 4. For neurological toxicities, withhold BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or Grade 4.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 infusion-related reactions. Permanently discontinue BAVENCIO for Grade 3 or Grade 4 infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) Grade 4 and nine (0.5%) Grade 3 infusion-related reactions. Eleven (92%) of the 12 patients with Grade ≥3 reactions were treated with intravenous corticosteroids.

Fatal and other serious complications of allogeneic hematopoietic stem cell transplantation (HSCT) can occur in patients who receive HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

BAVENCIO in combination with INLYTA can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Permanently discontinue BAVENCIO and INLYTA for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with INLYTA compared to 3.4% treated with sunitinib in a randomized trial. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

A fatal adverse reaction (sepsis) occurred in one (0.3%) patient with locally advanced or metastatic urothelial carcinoma (UC) receiving BAVENCIO + best supportive care (BSC) as first-line maintenance treatment. In patients with previously treated locally advanced or metastatic UC, fourteen patients (6%) who were treated with BAVENCIO experienced either pneumonitis, respiratory failure, sepsis/urosepsis, cerebrovascular accident, or gastrointestinal adverse events, which led to death.

The most common adverse reactions (all grades, ≥20%) in patients with locally advanced or metastatic UC receiving BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment were fatigue (35% vs 13%), musculoskeletal pain (24% vs 15%), urinary tract infection (20% vs 11%), and rash (20% vs 2.3%). In patients with previously treated locally advanced or metastatic UC receiving BAVENCIO, the most common adverse reactions (all grades, ≥20%) were fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection.

Selected laboratory abnormalities (all grades, ≥20%) in patients with locally advanced or metastatic UC receiving BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment were blood triglycerides increased (34% vs 28%), alkaline phosphatase increased (30% vs 20%), blood sodium decreased (28% vs 20%), lipase increased (25% vs 16%), aspartate aminotransferase (AST) increased (24% vs 12%), blood potassium increased (24% vs 16%), alanine aminotransferase (ALT) increased (24% vs 12%), blood cholesterol increased (22% vs 16%), serum amylase increased (21% vs 12%), hemoglobin decreased (28% vs 18%), and white blood cell decreased (20% vs 10%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with INLYTA. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with INLYTA (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with INLYTA (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

Please see full US Prescribing Information and Medication Guide available at View Source

About TEPMETKO (tepotinib)
TEPMETKO is a once-daily oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck KGaA, Darmstadt, Germany, TEPMETKO has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

TEPMETKO Approved Indications
TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal epithelial transition (MET) exon 14 skipping alterations. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

TEPMETKO was the first oral MET inhibitor to receive a regulatory approval anywhere in the world for the treatment of advanced NSCLC harboring MET gene alterations, with its approval in Japan in March 2020. In February 2021, the U.S. Food and Drug Administration granted accelerated approval to TEPMETKO, making it the first and only once-daily oral MET inhibitor approved for patients in the U.S. with metastatic NSCLC with METex14 skipping alterations. In February 2022, the European Commission (EC) approved once-daily oral TEPMETKO as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

TEPMETKO is available in a number of countries, and under review by various other regulatory authorities globally. To meet an urgent clinical need, TEPMETKO is also available in a pilot zone of China in line with the government policy to drive early access for innovative medicines approved outside of China.

Merck KGaA, Darmstadt, Germany is also investigating the potential role of tepotinib in treating patients with NSCLC and acquired resistance due to MET amplification in the Phase II INSIGHT 2 study of tepotinib in combination with osimertinib in MET amplified, advanced or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line treatment with osimertinib.

Important Safety Information from the US FDA-Approved Label
TEPMETKO can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ILD/pneumonitis occurred in 2.2% of patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death.

TEPMETKO can cause hepatotoxicity, which can be fatal. Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or total bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO. Increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST) occurred in 13% of patients treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in 4.2% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). The median time-to-onset of Grade 3 or higher increased ALT/AST was 30 days (range 1 to 178).

TEPMETKO can cause embryo-fetal toxicity. Based on findings in animal studies and its mechanism of action, TEPMETKO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the final dose.

Avoid concomitant use of TEPMETKO with dual strong CYP3A inhibitors and P-gp inhibitors and strong CYP3A inducers. Avoid concomitant use of TEPMETKO with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

Fatal adverse reactions occurred in one patient (0.4%) due to pneumonitis, one patient (0.4%) due to hepatic failure, and one patient (0.4%) due to dyspnea from fluid overload.

Serious adverse reactions occurred in 45% of patients who received TEPMETKO. Serious adverse reactions in >2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%).

The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea.

Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, rash, fever, dizziness, pruritus, and headache.

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (76%), increased creatinine (55%), increased alkaline phosphatase (ALP) (50%), decreased lymphocytes (48%), increased alanine aminotransferase (ALT) (44%), increased aspartate aminotransferase (AST) (35%), decreased sodium (31%), decreased hemoglobin (27%), increased potassium (25%), increased gamma-glutamyltransferase (GGT) (24%), increased amylase (23%), and decreased leukocytes (23%).

The most common Grade 3 to 4 laboratory abnormalities (≥2%) in descending order were: decreased lymphocytes (11%), decreased albumin (9%), decreased sodium (8%), increased GGT (5%), increased amylase (4.6%), increased ALT (4.1%), increased AST (2.5%), and decreased hemoglobin (2%).

A clinically relevant laboratory abnormality in <20% of patients who received TEPMETKO was increased lipase in 18% of patients, including 3.7% Grades 3 to 4.

For more information about TEPMETKO, please see full Prescribing Information, and visit www.TEPMETKO.com.

About Berzosertib (M6620)
Berzosertib is an investigational, intravenous, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type, and it is the lead candidate in Merck KGaA, Darmstadt, Germany’s DNA Damage Response (DDR) inhibitor portfolio. It is currently being investigated in a number of internal and external studies with early phase I/II data in small cell lung cancer, ovarian cancer, and various solid tumors. Berzosertib, formerly known as VX-970, was licensed from Vertex Pharmaceuticals in 2017. Berzosertib is not approved for any use anywhere in the world.

On May 26, 2022 GSK plc reported that it will present 25 abstracts at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (3-7 June) and nine abstracts at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress (9-12 June) focusing on approved therapies, Blenrep (belantamab mafodotin), Jemperli (dostarlimab) and Zejula (niraparib), as well as its investigational medicines (Press release, GlaxoSmithKline, MAY 26, 2022, View Source [SID1234615154]). The data presentations further demonstrate the company’s commitment to evaluate its approved and investigational therapies alone and in combination with other treatments and explore potential opportunities to improve patient care.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Hesham Abdullah, SVP, Global Head of Oncology Development, GSK said: "We have strategically built a portfolio and pipeline that leverages the science of the immune system, human genetics and advanced technologies to address a variety of tumour types. The data we will be sharing at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate how we’re delivering on our commitment to patients through novel approaches in some of the most promising areas of oncology research. We look forward to these important opportunities to come together and to share meaningful scientific updates with the broader oncology community."

Updates from the robust DREAMM clinical trial programme
Key presentations at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) include updates from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial programme evaluating belantamab mafodotin, an anti-BCMA (B-cell maturation antigen) therapy, in combination with both standard of care and investigational agents in earlier lines of therapy. Preliminary data from DREAMM-5 sub-study 3 of low-dose belantamab mafodotin in combination with nirogacestat in patients with relapsed/refractory multiple myeloma (ASCO abstract #8019) will be reported. Nirogacestat, an investigational gamma secretase inhibitor, has been shown to increase target density and reduce levels of soluble BCMA, and as such the potential to enhance the activity of BCMA-targeted therapies like belantamab mafodotin is under investigation.[i]

DREAMM-6 updates report outcomes from several dose cohorts of belantamab mafodotin in combination with lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who have received one or more prior lines of treatment (ASCO abstract #8017).

DREAMM-9, evaluating a quadruplet combination treatment regimen of belantamab mafodotin with standard of care (bortezomib, lenalidomide and dexamethasone or VRd) in patients with newly diagnosed multiple myeloma who are transplant ineligible, will also be presented at EHA (Free EHA Whitepaper) (EHA abstract #P942).

Collectively, the data from these trials are evaluating the efficacy and safety of belantamab mafodotin in patients with various lines of therapy, but also aim to assess how dose, scheduling and combination treatment may help to reduce corneal events associated with treatment. These data will be used to help inform further studies evaluating the potential of belantamab mafodotin in the multiple myeloma setting.

Blenrep received accelerated and conditional approvals in the US and EU, respectively, for adult patients with relapsed/refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 antibody, a proteasome inhibitor and an immunomodulatory agent. Studies are ongoing to verify clinical benefit.

Advancing research for patients with mismatch repair-deficient solid cancers
Results from the GARNET trial Cohorts A1 and A2 of dostarlimab, a programmed cell death receptor-1 (PD-1) blocking antibody, in advanced/recurrent (A/R) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer will be presented during a presentation at ASCO (Free ASCO Whitepaper) (ASCO abstract #5509). These results include the largest cohort of patients with dMMR A/R endometrial cancer treated with a PD-1 inhibitor monotherapy and will inform long-term use of dostarlimab in this patient population. In addition, long-term outcomes from the GARNET trial Cohorts A1 and F will be shared, covering the efficacy and safety profile of dostarlimab in certain patients with dMMR recurrent or advanced solid tumours, including endometrial cancer (ASCO abstract #2587). Results from Cohort A1 of the GARNET trial served as the basis for conditional approval in the EU for the treatment of certain patients with dMMR/MSI-H recurrent or advanced endometrial cancer, and for the accelerated approval in the US for certain patients with dMMR recurrent or advanced endometrial cancer. Additionally, results from Cohorts A1 and F served as the basis for the accelerated approval in the US for certain patients with dMMR recurrent or advanced solid tumours.

Realising the potential of synthetic lethality
GSK will also present real-world analyses from six studies in patients with advanced ovarian cancer at ASCO (Free ASCO Whitepaper), including real-world data evaluating outcomes in patients with advanced ovarian cancer who receive poly (ADP-ribose) polymerase (PARP) inhibitor monotherapy as maintenance compared to those who do not. Insights from the presentations will deepen the understanding of the use of PARP inhibitors for maintenance therapy in advanced ovarian cancer and shed light on differences in treatment practice across geographic locations.

Separately, a phase III PRIME study update will be shared by Zai Lab (a GSK partner) evaluating niraparib (independently manufactured by Zai Lab) in Chinese patients with newly diagnosed advanced ovarian cancer using an individualised starting dose in a poster presentation (ASCO abstract #5551).

Continued research on immuno-oncology investigational agents
GSK will also present findings from its early-stage pipeline assets, including a poster discussion on the AMBER study evaluating cobolimab, an investigational anti-TIM-3 targeting monoclonal antibody, in combination with dostarlimab in patients with advanced or metastatic melanoma (ASCO abstract #9513). TIM-3 is a key immune checkpoint and a novel immuno-oncology target that could play a critical role in the treatment of solid tumours. GSK is evaluating cobolimab for patients with different tumour types through various novel combinations, including doublets and triplets.

Collaborating to improve patient care

GSK is supporting investigator-sponsored studies and fostering scientific collaborations with both experienced investigators and networks, who are involved in the continuum of care of patients living with cancer. At ASCO (Free ASCO Whitepaper), updated data from an investigator-sponsored study from Memorial Sloan Kettering Cancer Center will be featured in a late-breaking oral presentation entitled "Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer" (ASCO abstract #LBA5). Initial data were presented earlier this year at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). There will be five additional GSK-supported investigator-sponsored studies presented at ASCO (Free ASCO Whitepaper).

At EHA (Free EHA Whitepaper), data from the BelaCarD investigator-sponsored study will report safety, tolerability and preliminary efficacy of belantamab mafodotin in combination with carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma (EHA abstract #P946). Additionally, an oral presentation on updated results from a supported collaborative study will evaluate the safety and efficacy of belantamab mafodotin plus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma (EHA abstract #S178).

Full list of GSK’s presentations at ASCO (Free ASCO Whitepaper):
Dostarlimab
Abstract Name

Presenter

Presentation Details

Comparison of Survival Outcomes Between Dostarlimab and Comparator Treatments (tx) in Patients (pts) with Advanced/Recurrent (A/R) Endometrial Cancer (EC) in England: Matching-Adjusted Indirect Comparisons (MAICs)

S. Goulden

Online publication, #e17534

Dostarlimab in Advanced/Recurrent (AR) Mismatch Repair Deficient/Microsatellite Instability–High or Proficient/Stable (dMMR/MSI-H or MMRp/MSS) Endometrial Cancer (EC): The GARNET Study

A. Oaknin

Clinical Science Symposium presentation, #5509

Efficacy and Safety of Dostarlimab in Patients (pts) with Mismatch Repair Deficient (dMMR) Solid Tumors: Analysis of 2 Cohorts in the GARNET Study

T. André

Poster presentation, #2587

Patient-Reported Outcomes from the GARNET Trial in Patients with Advanced or Recurrent Mismatch Repair Deficient (dMMR) Colorectal Cancer (CRC): A Post Hoc Subgroup Analysis

J. Hanlon

Poster presentation, #3558

Survival Outcomes for Dostarlimab and Real-World (RW) Treatment (tx) Paradigms in Post-Platinum Patients (pts) with Advanced/Recurrent (A/R) Endometrial Cancer (EC): The GARNET Trial versus an External Control Arm from the Flatiron Health Database

R. Coleman

Poster presentation, #5593

Understanding Patient Characteristics, Treatment Patterns, and Clinical Outcomes for Advanced and Recurrent Endometrial Cancer in Alberta, Canada

J. McGee

Online publication, #e17624

Belantamab Mafodotin
Abstract Name

Presenter

Abstract Number

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14

M. Hultcrantz

Poster presentation, #TPS8073

Safety and Clinical Activity of Belantamab Mafodotin with Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-6 Arm-A Interim Analysis

H. Quach

Poster discussion, #8017

Safety and Clinical Activity of Belantamab Mafodotin with Pembrolizumab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-4 Study

A. Suvannasankha

Poster discussion, #8018

Synergistic Effects of Low-Dose Belantamab Mafodotin in Combination with a Gamma-Secretase Inhibitor (Nirogacestat) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-5 Study

S. Lonial

Poster discussion, #8019

Niraparib
Abstract Name

Presenter

Presentation Details

MOONSTONE/GOG-3032: Interim Analysis of a Phase 2 Study of Niraparib + Dostarlimab in Patients (pts) with Platinum-Resistant Ovarian Cancer (PROC)

L. Randall

Poster presentation, #5573

Real-World Trends of PARPi Maintenance Treatment Uptake and Progression-Free Survival (PFS) in Patients (Pts) with Newly Diagnosed Advanced Ovarian Cancer (AOC) in the United States

J. Chan

Poster presentation, #6580

Treatment and Outcome of Patients with High Grade Advanced Ovarian Cancer (AOC) – Real World Data in Germany (QS Ovar of the AGO Study Group)

S. Mahner

Online publication, #e17613

Treatment Patterns and Time to Next Treatment Among Patients with OC in a Real-Life Setting in Finland: The OCRWE-Finland Study

H. Rauhamaa

Online publication, #e18806

Pipeline
Abstract Name

Presenter

Presentation Details

AMBER Parts 1C and 1E: A Phase 1 Study of Cobolimab plus Dostarlimab in Patients (pts) with Advanced/Metastatic Melanoma

A. Ribas

Poster discussion, #9513

Phase 1 Trial of TIM-3 Inhibitor Cobolimab Monotherapy and in Combination with PD-1 Inhibitors Nivolumab or Dostarlimab (AMBER)

G. Falchook

Oral presentation, #2504

Primary Efficacy and Safety of Letetresgene Autoleucel (lete-cel; GSK3377794) Pilot Study in Patients with Advanced and Metastatic Myxoid/Round Cell Liposarcoma (MRCLS)

S. D’Angelo

Oral presentation, #11500

Study Design of A Global Molecular Disease Characterization Initiative (MDCI) in Oncology Clinical Trials

D. Downs

Online publication, #e13598

ZENYTH-ESO: Master Protocol to Assess the Safety and Recommended Phase II Dose of Next Generation NY-ESO-1–Specific TCR T-cells in HLA-A*02 Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma [Substudy 3, GSK4427296]

D. Araujo

Poster presentation, #TPS2681

Full list of investigator-sponsored studies at ASCO (Free ASCO Whitepaper):
Abstract Name

Presenter

Presentation Details

AGO-OVAR 28 / ENGOT-ov57: Niraparib vs Niraparib in Combination with Bevacizumab in Patients with Carboplatin-Taxane Based Chemotherapy in Advanced Ovarian Cancer–A Multicentre Randomised Phase III Trial

F. Heitz

Poster presentation, #TPS5612

A Phase II Study Evaluating the Efficacy of Niraparib and Dostarlimab (TSR-042) in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

V. Karivedu

Poster presentation, #TPS6105

A Randomized Phase Ib/II Study of Niraparib (Nira) plus Either Nivolumab (Nivo) or Ipilimumab (Ipi) in Patients (Pts) with Platinum-Sensitive Advanced Pancreatic Cancer (aPDAC)

K. Reiss

Poster discussion, #4021

Results of a Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and other DNA Damage Response Pathway Deficient Neoplasms

T. George

Poster presentation, #3122

Role of Cytoreductive Surgery for the Second Ovarian Cancer Relapse in Patients Previously Treated with Chemotherapy Alone at First Relapse: A Subanalysis of the DESKTOP III Trial

J. Sehouli

Poster discussion, #5520

Single Agent PD-1 Blockade as Curative-Intent Treatment in Mismatch Repair Deficient Locally Advanced Rectal Cancer

A. Cercek

Late-breaking oral presentation, #LBA5

Full list of GSK’s presentations at EHA (Free EHA Whitepaper):
Abstract Name

Presenter

Presentation Details

DREAMM-9: Phase I Study of Belantamab Mafodotin Plus Standard of Care in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma​

S. Usmani

Poster session, #P942​

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14​

M. Hultcrantz

Online publication, #PB2022​

Safety and Clinical Activity of Belantamab Mafodotin with Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-6 Arm-A Interim Analysis

H. Quach

Poster session, #P941

Safety and Clinical Activity of Belantamab Mafodotin with Pembrolizumab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-4 Study​

A. Suvannasankha

Poster session, #P940​

Survival Outcomes of Patients with Multiple Myeloma in France: A Cohort Study Using the French National Healthcare Database (SNDS)​

X. Leleu

Poster session, #P943​

Synergistic Effects of Low Dose Belantamab Mafodotin in Combination with a Gamma-Secretase Inhibitor (Nirogacestat) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): DREAMM-5 Study​

A. Nooka

Poster session, #P939​

Full list of investigator-sponsored studies at EHA (Free EHA Whitepaper):
Abstract Name

Presenter

Presentation Details

A Phase I/II Single Arm Study of Belantamab Mafodotion, Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: AMARC 19-02 BelaCarD Study

M. Lasica

Poster session, #P946

Efficacy and Safety of Belantamab Mafodotin Monotherapy in Patients with Relapsed or Refractory Light Chain Amyloidosis: A Phase 2 Study by the European Myeloma Network

E. Kastritis

Poster presentation, #P914

Safety and Efficacy of Belantamab Mafodotin in Combination with RD in Newly Diagnosed, Transplant Ineligible Multiple Myeloma Patients: A Phase I/II Study by the Hellenic Society of Hematology

E. Terpos

Oral presentation, #S178

About multiple myeloma
Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable, but not curable.[ii],[iii] In the US, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year and nearly 13,000 people will die from the disease.[iv] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[v]

About ovarian cancer
Ovarian cancer is the 8th most common cancer in women worldwide.[vi] Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence.[vii] Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in the US and second most common gynaecologic cancer globally.[viii] Approximately 15-20% of women with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.[ix]

Important information for BLENREP in the EU
Indication
BLENREP is indicated as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Refer to the BLENREP Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

About Dostarlimab
Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.[x] In addition to GARNET, dostarlimab is being investigated in other registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers.

Dostarlimab was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1 antagonist; cobolimab (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these assets under the Agreement.

Important Information for JEMPERLI in the EU
Indication
JEMPERLI is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability‑high (MSI‑H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum‑containing regimen.

Refer to the JEMPERLI Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies.

Important Information for ZEJULA in the EU
Indication
ZEJULA is indicated as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

Refer to the ZEJULA Prescribing Information for a full list of adverse events and the complete important safety information in the EU.

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.

On May 26, 2022 Candel Therapeutics, Inc. (Nasdaq: CADL), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported the publication of abstract #9037 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7, 2022, in Chicago (Press release, Candel Therapeutics, MAY 26, 2022, View Source [SID1234615170]). The abstract summarizes initial data as of January 10, 2022, from Candel’s open-label phase 2 clinical trial evaluating CAN-2409 in combination with anti-PD-1 or PD-L1 agents in patients with stage III/IV non-small cell lung cancer (NSCLC) who have had an inadequate response to immune checkpoint inhibitor treatment. The data presented in the poster will include additional data not included in the abstract from a total of 20 patients as of April 20, 2022, including 16 patients from cohort 2.

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"The achievement of an 87.5 percent disease control rate in patients whose cancer was progressing on anti-PD-1 treatment at enrollment bolsters the evidence of CAN-2409’s potential to induce immunization against cancer neoantigens in both injected tumors and uninjected metastases so that resistance to checkpoint blockade can be overcome," said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel. "The occurrence of abscopal effects and clinically meaningful and durable activity, supported by significant biomarker responses and prior monotherapy activity data, strengthens our belief that this investigational agent has the potential to improve outcomes for patients with NSCLC who are progressing on anti-PD-1 agents."

Experimental treatment with CAN-2409 plus valacyclovir in combination with anti-PD-1 agents appeared to be well tolerated. The most common treatment-related adverse events were transient flu-like symptoms, such as chills, fever and fatigue, with no grade 4 and two grade 3 events reported.

Additional data highlights include:

Most patients experienced a reduction in tumor burden.
There were three objective responses in cohorts 1 and 2 (patients with stable disease or progressive disease upon entry, respectively). A fourth patient with PR initially reported in the abstract became ineligible for RECIST assessment due to an irradiated lesion; the patient still showed an absence of disease progression for more than 6 months.
Two of the three patients with a PR had PD-L1 expression below 1 percent, the third being unknown; 19 of 20 patients in the trial had negative or low PD-L1 expression.
CAN-2409 treatment induced 1) increased tumor infiltration by cytotoxic T cells, 2) a systemic increase in actively proliferating, granzyme B positive T cells, 3) an increase in interferon gamma producing effector cells in both CD4+ and CD8+ compartments, and 4) increased levels of soluble granzymes A, B and H, all consistent with the hypothesized mechanism of action of CAN-2409.
"As a physician who cares for patients with NSCLC, I am frequently confronted with the problem faced by the majority of patients with lung cancer who ultimately progress on immune checkpoint therapy," said Daniel Sterman, M.D., Professor at NYU Langone Heath, and a principal investigator for the phase 2 clinical trial. "The data from this clinical trial are incredibly exciting, suggesting that the addition of CAN-2409 to pembrolizumab or nivolumab containing treatment regimens in patients experiencing progression may offer a new therapeutic option where few good alternatives exist. Importantly, CAN-2409 was administered only two times in this setting, with intratumoral administration providing a simple and straightforward approach."

Details on the abstract are below:

Abstract Title: First report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC

Presenter: Charu Aggarwal, MD, MPH, Associate Professor of Lung Cancer Excellence, Perelman School of Medicine, University of Pennsylvania
Session Date and Time: June 6, 2022, from 8:00 – 11:00 am CDT
Session Title: Lung Cancer – Non-Small Cell Metastatic
Location: McCormick Convention Center, Hall A
Abstract Number: 9037
Candel also announced that an in-person and webcast investor event will be held on Saturday, June 4, 2022, from 6:30 – 7:45 am CDT.

Key speakers will be:

Dr. Roy Herbst, Professor of Medical Oncology and Chief of Medical Oncology at the Yale Cancer Center, and member of Candel’s Research Advisory Board
Dr. Daniel S. Sterman, Professor of Pulmonary and Critical Care Medicine, at the New York University, Director of the Multidisciplinary Pulmonary Oncology Program at NYU Langone Health, and a principal investigator on the phase 2 clinical trial
Dr. Paul Peter Tak, President and CEO of Candel Therapeutics
The webcast and slides will be accessible live under "Events and Presentations" on the Investors page of the company’s website at View Source or by clicking here. A replay will be available on the website for approximately 90 days after the event.

Dr. Charu Aggarwal is serving as the co-principal investigator of this phase 2 clinical trial. For more information on the clinical trial please visit: View Source

About CAN-2409

CAN-2409, Candel’s most advanced oncolytic viral immunotherapy candidate, is a replication-deficient adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to cancer cells. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This creates the optimal conditions to induce a specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, CAN-2409 presents a favorable tolerability profile; more than 700 patients have been dosed to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in non-small cell lung cancer, high-grade glioma, pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials.

On May 26, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a clinical-stage precision oncology company designing and developing novel targeted therapies for cancer treatment, reported that President and CEO Athena Countouriotis, M.D., will participate in the Jefferies Healthcare Conference on June 8 and the 43rd Annual Goldman Sachs Healthcare Conference on June 14 (Press release, Turning Point Therapeutics, MAY 26, 2022, View Source [SID1234615188]).

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Dr. Countouriotis is scheduled to present a company overview in New York on June 8 at 11 a.m. ET and scheduled to participate in a fireside chat on June 14 in Rancho Palo Verdes, California at 1 p.m. ET.

Both sessions will be accessible via webcast through links that will be posted to the Investors page of www.tptherapeutics.com.

On May 26, 2022 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported financial results for the quarter ended March 31, 2022 (Press release, Can-Fite BioPharma, MAY 26, 2022, View Source [SID1234615073]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"Can-Fite is financially well positioned to conduct all our clinical development programs over the next year, and we continue to evaluate potential new distribution partnerships which may provide additional non-dilutive funding."

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Corporate and Clinical Development Highlights Include:

Fortified Balance Sheet – On March 31, 2022, Can-Fite had approximately $16.5 million in cash, cash equivalents, and short-term deposits.

Phase III Psoriasis Study Data Expected Q2 2022 – Topline results are expected in Q2 2022 in Can-Fite’s Phase III Comfort psoriasis study for both its 16 week primary endpoint and 32 week secondary endpoint. The study is designed to establish Piclidenoson’s superiority compared to placebo at 16 weeks and non-inferiority compared to Apremilast (Otezla) at 32 weeks. During the first quarter, a preclinical study showed Piclidenoson destroyed pathological skin cells, offering further evidence of potential efficacy in psoriasis.

Developing Topical Psoriasis Treatment – In a preclinical model, daily treatment with topical Piclidenoson significantly inhibited psoriasis as measured by the psoriasis area severity index (PASI) calculated based on observation of erythema, thickness, scaling, and a score of skin lesions. The topical treatment may serve as a complementary product to oral Piclidenoson.

Commenced Enrollment in Phase IIb NASH Study – In January, Can-Fite enrolled the first patient in its Phase IIb multicenter, randomized, double-blind, placebo-controlled study in 140 subjects with biopsy-confirmed NASH. The primary objective of the trial is to evaluate the efficacy of Namodenoson as compared to placebo as determined by a histological endpoint. In a prior Phase IIa study, Namodenoson met its primary endpoint by reducing liver fat, inhibiting fibrosis, and demonstrating an anti-inflammatory effect.

Granted U.S. Patent for Liver Fibrosis and Israeli Patent for NASH – The U.S. Patent and Trademark Office granted Can-Fite a patent for its invention titled "Method for Treating Fibrotic Liver Tissue Using CL-IB MECA", a broad patent that addresses markets for the treatment of all advanced liver fibrosis indications. The patent opens an opportunity for much broader market needs which entail all clinical conditions with advanced liver fibrosis including autoimmune hepatitis, primary biliary cirrhosis (PBC), nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD) among others. The Israel Patent Office granted Can-Fite a patent titled "An A3 Adenosine Receptor Ligand For Use In Treating Ectopic Fat Accumulation" which has been issued in approximately 40 other countries.

Opened Enrollment in Pivotal Phase III Liver Cancer Study – Can-Fite’s pivotal Phase III liver cancer study for Namodenoson opened for enrollment of approximately 450 patients diagnosed with hepatocellular carcinoma (HCC) and underlying Child Pugh B7 (CPB7) who have not responded to other approved therapies. An interim analysis will be conducted after 50% of patients are enrolled and treated. The primary endpoint is overall survival. Can-Fite has received Orphan Drug Designation in both the U.S. and Europe and has received the U.S. FDA’s Fast Track Status.

Presented Data on Cannabinoids in the Treatment of Liver Cancer at CannX – In March, Can-Fite delivered a presentation titled "Inhibition of Hepatocellular Carcinoma Growth and Liver Fibrosis by Nanomolar Cannabinoids Concentrations" at the CannX Medical Cannabis Conference in Tel Aviv. The findings were also published in the peer-reviewed scientific journal Medical Cannabis and Cannabinoids highlighting the ability of CBD-rich T3/C15 in nanomolar concentrations to inhibit the growth of hepatocellular carcinoma and liver stellate cells via A3AR activation and deregulation of the Wnt/β-catenin pathway.

"We look forward to announcing Phase III psoriasis results before the end of the second quarter as we enroll patients in our other advanced stage clinical trials for NASH and liver cancer," stated Can-Fite CEO Dr. Pnina Fishman. "Can-Fite is financially well positioned to conduct all our clinical development programs over the next year, and we continue to evaluate potential new distribution partnerships which may provide additional non-dilutive funding."

Financial Results

Revenues for the three months ended March 31, 2022 were $0.20 million, an increase of $0.05 million, or 38.5%, compared to $0.15 million for the three months ended March 31, 2021. The increase in revenues was mainly due to the recognition of a higher portion of advance payments received under a distribution agreement with Ewopharma than the advance payment received at the end of the first quarter of 2021.

Research and development expenses for the three months ended March 31, 2022 were $1.82 million, an increase of $0.52 million, or 39.8%, compared to $1.30 million for the three months ended March 31, 2021. Research and development expenses for the first quarter of 2022 comprised primarily of expenses associated with an ongoing Phase III study of Piclidenoson for the treatment of psoriasis and two studies for Namodenoson, a Phase III study in the treatment of liver cancer and a Phase IIb study for NASH. The increase is primarily due to costs incurred in the first quarter of 2022 associated with the two new studies for Namodenoson.

General and administrative expenses for the three months ended March 31, 2022 were $0.75 million a decrease of $0.26 million, or 25.8%, compared to $1.01 million for the three months ended March 31, 2021. The decrease is primarily due to the decrease in professional services for public relations and investor relations. We expect that general and administrative expenses will remain at the same level through 2022.

Financial expenses, net for the three months ended March 31, 2022 were $0.06 million compared to finance income, net of $0.29 million for the three months ended March 31, 2021. The decrease in financial income, net was mainly due to revaluation of our short-term investment which in 2021 was recorded as income and in 2022 was recorded as expense.

Net loss for the three months ended March 31, 2022 was $2.43 million compared with a net loss of $1.87 million for the three months ended March 31, 2021. The increase in net loss for the three months ended March 31, 2022 was primarily attributable to an increase in research and development expenses which was partly offset by a decrease in general and administrative expenses and a decrease in finance income, net.

As of March 31, 2022, Can-Fite had cash and cash equivalents and short term deposits of $16.5 million as compared to $18.9 million at December 31, 2021. The decrease in cash during the three months ended March 31, 2022 is due to the ongoing operation of the Company.

The Company’s consolidated financial results for the three months ended March 31, 2022 are presented in accordance with US GAAP Reporting Standards.