On September 7, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported the positive overall survival (OS) results from the Phase 3 TROPiCS-02 study evaluating Trodelvy (sacituzumab govitecan-hziy) versus comparator chemotherapy (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who received endocrine-based therapies and at least two chemotherapies (Press release, Gilead Sciences, SEP 7, 2022, View Source;Metastatic-Breast-Cancer-Patients-in-TROPiCS-02-Study [SID1234619200]). In the study, Trodelvy demonstrated a statistically significant and clinically meaningful improvement of 3.2 months in OS compared to TPC (median OS: 14.4 months vs. 11.2 months; hazard ratio [HR]=0.79; [95% confidence interval [CI]: 0.65-0.96]; p=0.02). OS was a key secondary endpoint of the trial.

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These findings will be presented on Friday, September 9 at 4:20pm CEST during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 as a late-breaking oral presentation (#LBA76) in the Brest Auditorium, Paris Expo Porte de Versailles.

Other key secondary endpoints including objective response rate (ORR) demonstrated statistically significant improvement in favoring Trodelvy versus TPC. Time to deterioration (TTD) of Global Health Status/Quality of Life (QoL) and Fatigue scale per EORTC-QLQ-C30 also favored Trodelvy versus TPC (QoL: 4.3 months vs. 3.0 months, p=0.006; Fatigue: 2.2 months vs. 1.4 months, p=0.002). No statistically significant difference in TTD on the Pain Scale was observed.

"It is outstanding to see a clinically meaningful survival benefit of over three months for patients with pre-treated HR+/HER2- metastatic breast cancer," said Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, U.S. "Nearly all patients with HR+/HER2- metastatic breast cancer will develop resistance to endocrine-based therapies even in combination with targeted agents, so these data are welcome news for the breast cancer community. The results of TROPiCS-02 highlight the potential for sacituzumab govitecan in patients with pre-treated HR+/HER2- metastatic breast cancer."

The safety profile for Trodelvy was consistent with prior studies, with no new safety signals identified in this patient population.

"With these data from TROPiCS-02, Trodelvy has now demonstrated a survival benefit in both pre-treated HR+/HER2- metastatic breast cancer and second-line metastatic TNBC – two difficult-to-treat forms of breast cancer," said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. "Our Gilead Oncology ambition is to transform care for people with cancer, and the meaningful improvement in survival benefit seen in the TROPiCS-02 study with Trodelvy is another step forward in pursuing this ambition for patients."

The TROPiCS-02 study met its primary endpoint of progression-free survival earlier this year; detailed results were presented during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Gilead has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) based on data from TROPiCS-02; these data will also be shared with health authorities outside the U.S.

Sacituzumab govitecan-hziy is currently included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines)i. This includes a Category 1 recommendation for use in adult patients with second-line metastatic triple-negative breast cancer (defined as those who received at least two prior therapies, with at least one line for metastatic disease). It also has a Category 2A preferred recommendation for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy.

Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About HR+/HER2- Breast Cancer

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases, or nearly 400,000 diagnoses worldwide each year. Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%. As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.

About the TROPiCS-02 Study

The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test. More information about TROPiCS-02 is available at View Source

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in more than 35 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

Trodelvy is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

On September 7, 2022 Merck, a leading science and technology company, reported the latest research from the Company’s oncology portfolio and pipeline to be presented at this year’s European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting, September 9-13, 2022 (Press release, Merck & Co, SEP 7, 2022, View Source [SID1234619199]). A total of 29 abstracts, including 5 late-breaking oral presentations and 2 additional mini-oral presentations, will feature data from company- and investigator-sponsored studies across six approved or investigational medicines in multiple tumor types.

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"Our ESMO (Free ESMO Whitepaper) 2022 data will highlight the strong potential of our innovative pipeline for patients with cancers with significant unmet needs," said Victoria Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare business of Merck. "From our IAP inhibitor xevinapant, studied in a curative setting in locally advanced head and neck cancer; through to new data in NSCLC patients with MET amplification and EGFR mutations; to our potentially best-in-class oral ATR inhibitor; we are focused on unlocking novel mechanisms of action that exploit the vulnerabilities of cancer."

The company’s late-breaking data at the congress feature five-year overall survival (OS) results from a Phase II study of the IAP (Inhibitor of Apoptosis Protein) inhibitor xevinapant in patients with unresected locally advanced squamous cell carcinoma of the head and neck [Mini Oral #LBA33]. Patients who received xevinapant plus chemoradiotherapy (CRT) had improved efficacy outcomes compared with those who received placebo with CRT.

Additional late-breaking results include initial results from the Phase II INSIGHT 2 trial of TEPMETKO (tepotinib) plus osimertinib in the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC) with MET amplification (METamp) after progression on first-line treatment with osimertinib [Proffered Paper #LBA52]. The confirmed overall response rate (ORR) was 54.5% (95% CI, 32.2, 75.6) in 22 patients with METamp detected by FISH (MET GCN ≥5 and/or MET/CEP7 ≥2) in tissue biopsy who received tepotinib plus osimertinib and were followed for at least nine months, with six of 12 responders still on treatment. Among the 48 patients followed for at least three months, ORR was 45.8% (95% CI, 31.4, 60.8). The most common treatment-related adverse events of any grade in greater than 15% of patients were diarrhea (40.9%), peripheral edema (23.9%) and paronychia (17.0%).

Further late-breaking data to be presented at ESMO (Free ESMO Whitepaper) 2022 include translational data for BAVENCIO (avelumab) characterizing genomic biomarkers in peripheral blood from patients enrolled in the Phase III JAVELIN Bladder 100 trial [Proffered Paper #LBA74].

Additional key data to be presented:

A mini-oral presentation from the first-in-human Phase I study of M1774, the Company’s potentially best-in-class potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) showing a favorable safety profile and pharmacologically relevant exposure, in patients with advanced solid tumors (DDRiver Solid Tumors 301) [#457MO] exemplifying the Company’s commitment to advancing understanding of DNA Damage Response (DDR) inhibition mechanisms.
Exploratory analyses from JAVELIN Bladder 100 that examine clinical outcomes in long-term responders with advanced urothelial carcinoma treated with BAVENCIO first-line maintenance for ≥12 months [#1760P]. Long-term follow-up data presented earlier this year reinforced the benefit of BAVENCIO plus best supportive care (BSC) in the first-line maintenance setting, with a continued improvement in OS versus BSC alone for patients with locally advanced or metastatic urothelial carcinoma whose tumors had not progressed on a platinum-based chemotherapy.1
Results from cohorts A and C in the Phase II VISION trial demonstrated robust and durable efficacy in treatment-naïve and previously treated patients with metastatic NSCLC with METex 14-skipping. In previously treated patients, efficacy was observed regardless of prior therapies including IO and/or platinum-based CT [#985P].
Other company-sponsored events at ESMO (Free ESMO Whitepaper) 2022 include:

Medical Symposia:

From Complex to Simple: The Journey to Strategic Sequencing in the Management of mCRC (Friday, September 9, 6:00–7:30 PM CEST, 7.3Q Quimper Auditorium, Hall 7, Level 7.3)
New Approaches to Optimize Treatment Outcomes in Advanced Urothelial Carcinoma (Saturday, September 10, 1:00-2:30 PM CEST, 7.3.U Urval Auditorium, Hall 7, Level 7.3)
Evolution of SCCHN Treatment (Sunday, September 11, 6:30-8:00 PM CEST, 7.3.0 Orleans Auditorium, Hall 7, Level 7.3).
Continuing Medical Education (CME):

Navigating Treatment Decisions in Advanced NSCLC: Update on Molecular Testing and New Targeted Treatment Options (Friday, September 9, 10:15-11:45 AM CEST, Quimper Auditorium, Hall 7, Level 7.3)
Select presentations (all times CEST):

Title

Lead Author

Abstract

Session Title/Date/Time

PIPELINE

5-year overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) treated with xevinapant+chemoradiotherapy (CRT) vs placebo+CRT in a randomized, phase 2 study

J Bourhis

LBA33

Mini Oral Session: Head and Neck Cancer

Saturday, 10 September

10:55 AM

A First-in-Human Phase I Study of ATR Inhibitor M1774 in Patients with Advanced Solid Tumors

(DDRiver Solid Tumors 301)

TA Yap

457MO

Mini Oral Session:

Developmental Therapeutics

Monday, 12 September

4:55 PM

Phase 1 study of TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa (BA) in patients (pts) with metastatic/locally advanced solid unresectable tumours

LL Siu

750P

Investigational immunotherapy

Monday, 12 September

BAVENCIO (avelumab)

Characterization of genomic biomarkers in peripheral blood (PB) from patients (pts) enrolled in the JAVELIN Bladder 100 trial of avelumab first-line (1L) maintenance in advanced urothelial carcinoma (aUC)

T Powles

LBA74

Proffered Paper Session 1: GU tumours, non-prostate

Saturday, 10 September

11:10 AM

Avelumab versus standard second line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): the SAMCO-PRODIGE 54 randomised phase II trial

J Taïeb

LBA23

Proffered Paper Session 1: GI lower digestive

Sunday, 11 September

11:15 AM

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): results from patients with ≥12 mos of treatment in JAVELIN Bladder 100

J Aragon-Ching

1760P

Urothelial Cancer

Monday, 12 September

Preliminary results from AVENANCE, an ongoing, noninterventional real-world, ambispective study of avelumab first-line (1L) maintenance treatment in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC)

P Barthélémy

1757P

Urothelial Cancer

Monday, 12 September

Avelumab added to FOLFIRI plus cetuximab followed by avelumab maintenance in patients with previously

untreated RAS wild-type colorectal cancer–The phase-II FIRE-6 (AIO KRK-0118)

S Stintzing

424P

Colorectal Cancer

Sunday, 11 September

TEPTMETKO (tepotinib)

Tepotinib+osimertinib for EGFR-mutant(m) NSCLC after progression on first-line (1L) osimertinib due to MET amplification: Initial results from the INSIGHT 2 study

J Mazieres

LBA52

Proffered Paper Session: NSCLC, metastatic

Sunday, 11 September

2:55 PM

Tepotinib outcomes according to prior therapies in patients with METexon14 (METex14) skipping NSCLC

E Smit

985P

NSCLC, metastatic

Monday, 12 September

ERBITUX (cetuximab)

Phase III study with FOLFIRI/Cetuximab versus FOLFIRI/Cetuximab followed by Cetuximab (Cet) alone in first-line therapy of RAS and BRAF wild type (wt) metastatic colorectal cancer (mCRC) patients: the ERMES Study (NCT02484833)

A Orlandi

LBA22

Proffered Paper Session 1: GI, lower digestive

Sunday, 11 September

10:25 AM

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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. In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications

The European Commission (EC) has authorized the use of BAVENCIO as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. BAVENCIO in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is also authorized by the EC for use as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

In the US, BAVENCIO is indicated 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 RCC. Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication 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 Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

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, 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 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 US 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.

TEPMETKO is available in a number of countries. 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 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.

TEPMETKO Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for TEPMETKO monotherapy include Interstitial lung disease (ILD) or ILD-like adverse reactions including pneumonitis, increase of Liver enzymes (ALT and AST), QTc prolongation, and embryo-foetal toxicity.

The most common adverse reactions in ≥ 20% of exposed to tepotinib at the recommended dose in the target indication are oedema, mainly peripheral oedema, nausea, hypoalbuminaemia, diarrhoea and increase in creatinine. The most common serious adverse reactions in ≥ 1% of patients are peripheral oedema, generalised oedema and ILD.

About ERBITUX (cetuximab)

ERBITUX is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

ERBITUX has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market ERBITUX, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.

About Xevinapant

Xevinapant (formerly known as Debio 1143) is an investigational first-in-class potent oral small-molecule IAP (inhibitor of apoptosis protein) inhibitor for the treatment of LA SCCHN. In preclinical studies, xevinapant restored sensitivity to apoptosis in cancer cells, thereby enhancing the effects of chemotherapy and radiotherapy. Xevinapant, the most clinically advanced IAP inhibitor, improved efficacy outcomes in combination with chemoradiotherapy (CRT), including three-year progression-free survival and five-year survival, compared with placebo plus CRT in a Phase II study in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). In March 2021, Merck gained exclusive rights from Debiopharm to develop and commercialize xevinapant worldwide. Xevinapant is not approved for any use anywhere in the world.

On September 7, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company focused on developing and commercializing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide, reported that the Company will participate in the Morgan Stanley 20th Annual Global Healthcare Conference on Wednesday, September 14th, 2022 with a fireside chat at 9:10 a.m. ET (Press release, BeiGene, SEP 7, 2022, View Source [SID1234619198]).

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A live webcast can be accessed from the investors section of BeiGene’s website at View Source An archived replay will be available for 90 days following the event.

On September 7, 2022 Genexine (KOSDAQ: 095700), a publicly traded, clinical-stage Korean biopharmaceutical company committed to the discovery and development of novel biologics for the treatment of unmet medical needs, reported that GX-188E, its first-in-class proprietary DNA vaccine, demonstrated potent efficacy and favorable safety in patients with advanced cervical cancer in a phase 2 study when given in combination with KEYTRUDA (pembrolizumab), MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy (Press release, Genexine, SEP 7, 2022, View Source [SID1234619197]).

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A total of 60 patients with HPV 16- and/or 18- positive advanced cervical cancer were analyzed in the phase 2 treatment group. Top line results showed a Best Overall Response Rate (BORR) of 31.7% (19 of 60 patients). 6 patients (10.0%) had a complete response and 13 patients (21.7%) had a partial response. Median duration of response (DOR) was 12.3 months and overall survival (OS) was 17.2 months.

The BORR increased to 38.5% in PD-L1 positive patients with HPV 16+ and Squamous Cell Carcinoma. Importantly, PD-L1 negative patients showed an ORR of 25.0%, which is extremely encouraging for this patient population, as it demonstrates potential improvement in efficacy compared to monotherapy of immune checkpoint inhibitors, suggesting a beneficial effect of the combination therapy.

In the safety analysis (n=65) 22 of 65 patients (33.8%) had treatment-related adverse events (TRAEs) of any grade and three (4.6%) had grade 3 or 4 TRAEs. The combination therapy was found to be safe and tolerable with a similar safety profile to that of pembrolizumab monotherapy.

"There is an urgent need for better therapies for patients with advanced cervical cancer and the combination of a therapeutic DNA vaccine together with checkpoint inhibition could be a strong alternative," said professor Sung-Jong Lee of the Catholic University of Korea, College of Medicine and Investigator in the trial. "The data are very encouraging and appear to show a clear efficacy signal and the product appears safe and well tolerated. I am particularly pleased to see a clear efficacy signal in all patients, regardless of PD-L1 expression. Genexine’s combination therapy has strong appeal from a mechanistic perspective. This approach of using checkpoint inhibition to restore immune system function combined with the vaccine’s effect of upregulating and increasing the influx of CD8+ and other immune cells into the tumor microenvironment, appears to result in a strong, beneficial effect as demonstrated by major outcome measures such as BORR (31.7%) and OS (17.2 months) through the elimination of tumor cells and tumors."

"We are very pleased to have been invited to present our phase 2 top-line data at ESMO (Free ESMO Whitepaper) and encouraged by the efficacy and safety shown in this study," said Neil Warma, President and CEO of Genexine. "The combination of GX-188E, our unique DNA vaccine, with pembrolizumab could represent a new standard of care for patients with HPV 16/18 related recurrent or metastatic cervical cancer, regardless of PD-L1 expression. We are encouraged by the ORR of over 31% but particularly excited by the efficacy signal observed in PD-L1 negative patients. This could open the door to a new therapy for this patient population that previously had limited treatment options available."

The clinical trial was an open-label, single-arm, phase 2 trial conducted in South Korea in patients with HPV-16 or HPV-18 positive advanced cervical cancer, and who had progressed after standard-of-care therapy. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and optional dose at week 46, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was ORR assessed by the blinded independent central reviewers (BICR) using RECIST version 1.1.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ.

On September 7, 2022 CytoImmune Therapeutics, a clinical-stage immuno-oncology company that is developing a novel class of engineered natural killer (NK) cell-based cancer therapies, reported the appointment of Remus Vezan, M.D., Ph.D., as Chief Medical Officer (Press release, CytoImmune Therapeutics, SEP 7, 2022, View Source [SID1234619196]). Dr. Vezan is an industry leader who has been responsible for the successful advancement of numerous cell therapies from early-stage development through commercialization, including one of the first U.S. Food and Drug Administration (FDA)- approved CAR T-cell therapies for hematologic malignancies.

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"Remus brings an ideal combination of expertise to CytoImmune, having led the successful implementation and execution of clinical development strategies for several biopharmaceutical companies focused on both immuno-oncology and cell therapies," said Christina Coughlin, M.D., Ph.D., Chief Executive Officer of CytoImmune. "We recently made the important transition to a clinical-stage company with the initiation of our Phase 1 trial of CYTO-102 for non-small cell lung cancer, and I am excited to partner with Remus as we advance this program and others in our pipeline."

"CytoImmune is taking a novel approach to developing cell therapies, leveraging NK cells to create medicines that directly attack cancer cells and broadly stimulate both the innate and adaptive arms of the immune system," said Dr. Vezan. "Cell therapies have proven highly effective in treating various hematologic malignancies, with several approved products available today, however, the results obtained in solid tumors to date are underwhelming. Through novel engineering and manufacturing strategies, CytoImmune’s engineered NK cell therapies have the potential to overcome key challenges that have been observed in solid tumors. This will greatly expand the number of patients who could benefit from this therapy. I am pleased to join the team at this exciting time in the evolution of the company."

Dr. Vezan joins CytoImmune from CERo Therapeutics where he served as Chief Medical Officer. Prior to that, he served as Executive Director of clinical development at Kite, a Gilead company, where he oversaw the clinical development of CAR T-cell products, including axi- cell/YESCARTA, the first CAR T-cell therapy approved for relapsed/refractory B-cell lymphoma and brexu-cell/TECARTUS, the first CAR T-cell therapy approved for mantle cell lymphoma and adult acute lymphoblastic leukemia. In this role, Dr. Vezan supported the overall clinical development strategy and execution of numerous registrational clinical trials and under his leadership, YESCARTA and TECARTUS were granted various global approvals. Before Kite, Dr. Vezan served as Medical Director at Pharmacyclics, an AbbVie Company, where he was the clinical lead for HDACi-abexinostat program and ibrutinib (IMBRUVICA) in lymphoplasmacytic lymphomas (Waldenstrom Macroglobulinemia). Dr. Vezan completed his medical training (M.D. and Ph.D.) at the University of Medicine and Pharmacy Cluj, Romania and University of Bern, Switzerland.