On September 18, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), reported the presentation of nine month follow-up data from the Company’s Phase 3 INVICTUS study of QINLOCK in patients with fourth-line and fourth-line plus gastrointestinal stromal tumors (GIST) and intra-patient dose escalation data from the ongoing Phase 1 study of QINLOCK in patients with second-line through fourth-line plus GIST (Press release, Deciphera Pharmaceuticals, SEP 18, 2020, View Source [SID1234565345]). The mini-oral presentations, titled "Clinical Benefit with Ripretinib as ≥4th Line Treatment in Patients with Advanced Gastrointestinal Stromal Tumors (GIST): Update from the Phase 3 INVICTUS Study" and "Ripretinib Intra-patient Dose Escalation (IPDE) Following Disease Progression Provides Clinically Meaningful Progression-Free Survival (PFS) in Gastrointestinal Stromal Tumor (GIST) in Phase 1 Study", were featured at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020 being held September 19-21, 2020.

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"As the body of data supporting QINLOCK’s efficacy and safety grows, we are pleased with QINLOCK’s ability to offer clinically meaningful benefit for GIST patients across multiple lines of therapy," said Matthew L. Sherman, MD, Executive Vice President and Chief Medical Officer of Deciphera. "Data presented today demonstrates impressive long-term, follow-up results from our INVICTUS study, which support QINLOCK’s efficacy in fourth-line GIST."

INVICTUS Additional Nine Month Follow-up Data

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of QINLOCK compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The Company previously reported results from the randomized portion of the INVICTUS study, in which QINLOCK significantly improved progression-free survival (PFS) and showed a clinically meaningful overall survival (OS) benefit.

As of a March 9, 2020 cutoff date, approximately nine months from the data cutoff date for the primary analysis, QINLOCK continues to provide clinically meaningful benefit with a well-tolerated safety profile in patients with advanced GIST who have received at least three prior tyrosine kinase inhibitors. The median PFS, as measured by blinded independent central review, remained at 6.3 months versus 1.0 month in the placebo arm. The hazard ratio (HR) was 0.16. The median OS as of the data cutoff was not reached in the QINLOCK arm versus 6.3 months in the placebo arm with a HR of 0.42, as compared to the median OS at the May 2019 data cutoff for the primary analysis of 15.1 months in the QINLOCK arm versus 6.6 months in the placebo arm with a HR of 0.36. QINLOCK also demonstrated a confirmed objective response rate of 11.8% versus 0% in the placebo arm compared to rates of 9.4% versus 0% in the placebo arm as of the data cutoff date for the primary analysis.

Safety findings were consistent with the previous primary analysis results, demonstrating that QINLOCK was generally well tolerated.

Phase 1 Intra-patient Dose Escalation

In the ongoing Phase 1 study of QINLOCK in patients with second-line through fourth-line plus GIST, patients were permitted to dose escalate to QINLOCK 150 mg twice-daily, or BID, after disease progression on QINLOCK 150 mg once-daily, or QD. The presentation highlighted that the patients in second-, third- or fourth-line plus GIST who dose escalated to QINLOCK 150 mg BID experienced additional clinically meaningful benefit.

The table below includes the initial PFS, or PFS1, and the subsequent PFS, or PFS2, from the day of dose escalation to second disease progression or death, from this subgroup of patients who were dose escalated to 150 mg BID.

Ripretinib 150 mg BID (n=67)

Line of Therapy

2nd line (n=10)

3rd line (n=17)

≥4th line (n=40)

mPFS, months

mPFS1, 11.0
mPFS2, 5.6

mPFS1, 8.3
mPFS2, 3.3

mPFS1, 5.5
mPFS2, 4.6

mPFS2/mPFS1

51%

40%

84%

mPFS=median progression-free survival

Comparison of TEAEs reported in the QINLOCK 150 mg QD and 150 mg BID periods demonstrated that QINLOCK was similarly well-tolerated.

About QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation involved in systemic mastocytosis, or SM. QINLOCK also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

QINLOCK is approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. It is also approved by Health Canada for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib and by the Australian Therapeutic Goods Administration for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib.

Deciphera Pharmaceuticals is developing QINLOCK for the treatment of KIT and/or PDGFRα-driven cancers, including GIST, SM, and other cancers. Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of QINLOCK in Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for QINLOCK in the rest of the world.

U.S. Indication and Important Safety Information About QINLOCK

Indications and Usage

QINLOCK (ripretinib) is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. For more information visit QINLOCK.com.

Important Safety Information

There are no contraindications for QINLOCK.

Palmar-plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who received QINLOCK. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold QINLOCK and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received QINLOCK with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue QINLOCK at the same dose.

Hypertension: In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received QINLOCK. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating QINLOCK and during treatment, as clinically indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: QINLOCK 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 and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. QINLOCK may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of QINLOCK in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong CYP3A inducers.

Please click here to see the full U.S. Prescribing Information for QINLOCK.

About the INVICTUS Phase 3 Study

INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily. The primary efficacy endpoint was progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 80% of cases, or in PDGFRα kinase, representing approximately 6% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

On September 18, 2020 IO Biotech, a clinical-stage biopharmaceutical company developing novel, immune-modulating anti-cancer therapies based on its proprietary T-win technology, reported a late-breaking, oral presentation of best-in-class efficacy data in first line melanoma for its cancer vaccines, IO102 and IO103 in combination with anti-PD1, nivolumab (Press release, IO Biotech, SEP 18, 2020, View Source [SID1234565344]). According to the abstract, the combination of IO102 and IO103 vaccines and nivolumab was shown to be safe with encouraging early efficacy data; an overall response rate (ORR) of 79 percent was reached and 45 percent of patients achieved a complete response (CR), or complete disappearance of their tumors. Vaccine specific T-cells were located in peripheral blood mononuclear cells (PBMCs) and at the tumor site. These data will be presented as a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 by Professor Inge Marie Svane, MD, Copenhagen University Hospital, Herlev. The abstract was published today online via the ESMO (Free ESMO Whitepaper) website (presentation number LBA48).

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As of the data cut-off in August 2020, 30 patients were enrolled with a median follow up time of 15 months. One patient is pending first evaluation, 29 were evaluated, and by investigator review per RECIST v1.1, an ORR of 79 percent was reached; ORR was 94 percent and 62 percent in PD-L1 positive and negative patients, respectively. At data cut-off, 45 percent had reached a complete response and 34 percent achieved a partial response, which was significantly higher than a matched control group extracted from the Danish Metastatic Melanoma Database receiving anti-PD-1 monotherapy treatment as standard of care. The median progression free survival (mPFS) was 25.6 months. Except for local reactions at the vaccination site, toxicity was comparable to patients receiving nivolumab monotherapy. Vaccine specific T-cells against either IDO and/or PD-L1 were detectable from all treated patients in PBMCs and in several patients’ tumor sites where a biopsy was feasible. Preliminary results from tumor immune contexture analyses were also indicative of response.

"These early results are extremely encouraging and point toward a significant advantage of adding the vaccine to standard anti-PD1 therapy," said Professor Inge Marie Svane, MD, Director at Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev, Denmark. "Not only have we seen almost twice as many patients benefitting from the treatment as expected, but it is also important to note that the combination was very well tolerated by the patients."

"We are very pleased that the MM1636 study is selected as a late-breaking abstract at ESMO (Free ESMO Whitepaper)," said Mai-Britt Zocca, PhD, Chief Executive Officer and founder at IO Biotech. "There is a high unmet need for a more effective treatment for melanoma patients, and our data demonstrate clearly our anticipated hypothesis of our T-win compounds to add additional efficacy to anti-PD1 treatment without any observed safety concerns."

About MM1636 trial
The MM1636 trial is an investigator-initiated trial at the Copenhagen University Hospital, Herlev and enrolled 30 patients with metastatic melanoma. In this Phase 2 clinical trial, patients are receiving the anti programmed death 1 (PD-1) antibody nivolumab in combination with a multi antigen vaccine, IO102 and IO103, as first line treatment. Patients are being treated with nivolumab every second week as long as there is a clinical benefit or no adverse events prohibiting further treatment. IO102 and IO103 are given from the start of administration of nivolumab and every second week for the first six vaccines and thereafter every fourth week up to one year. The trial objectives are to assess safety, immune response in blood and biopsies as well as efficacy.

About IO102 and IO103
IO102 is a first-in-class, second-generation immune modulatory vaccine containing a single Indoleamine 2,3-dioxygenase (IDO) derived peptide sequence designed to engage and activate IDO specific human anti-regulatory T-cells.

IO103 is a first-in-class, immune modulatory vaccine containing a single PD-L1-derived peptide designed to engage and activate PD-L1 specific human anti-regulatory T-cells.

Both compounds are based on IO Biotech’s proprietary T-win technology platform which enables the identification of compounds with a dual mechanism of action targeting and directly killing immunosuppressive cells and tumor cells while indirectly activating other T-effectors, leading to strong anti-tumor responses. The company’s compounds are administered as "off-the-shelf" subcutaneous injections, distinguishing these treatments from many immuno-oncology therapies.

On September 18, 2020 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:SGEN) reported that a phase 3 trial of PADCEV (enfortumab vedotin-ejfv) met its primary endpoint of overall survival compared to chemotherapy (Press release, Astellas, SEP 18, 2020, View Source [SID1234565343]). The results were reviewed by an independent Data Monitoring Committee following a planned interim analysis. The global EV-301 clinical trial compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor.

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In the trial, PADCEV significantly improved overall survival (OS), with a 30 percent reduction in risk of death (Hazard Ratio [HR]=0.70; [95% Confidence Interval (CI): 0.56, 0.89]; p=0.001). PADCEV also significantly improved progression-free survival (PFS), a secondary endpoint, with a 39 percent reduction in risk of disease progression or death (HR=0.61 [95% CI: 0.50, 0.75]; p<0.00001).

For patients in the PADCEV arm of the trial, adverse events were consistent with those listed in the U.S. Prescribing Information, with rash, hyperglycemia, decreased neutrophil count, fatigue, anemia and decreased appetite as the most frequent Grade 3 or greater adverse event(s) occurring in more than 5 percent of patients. Data from EV-301 will be submitted for presentation at an upcoming scientific congress. Patients in the chemotherapy arm of the trial will be offered the opportunity to receive PADCEV.

The results will be submitted to the U.S. Food and Drug Administration (FDA) as the confirmatory trial following the drug’s accelerated approval in 2019. EV-301 is also intended to support global registrations.

"EV-301 is the first randomized trial to show overall survival results compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who previously have received platinum-based treatment and a PD-1 or PD-L1 inhibitor, and we are encouraged by the potential this may have in helping patients who have otherwise limited alternatives," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these results with global health authorities."

"These survival results from the confirmatory trial for PADCEV are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "We continue to explore PADCEV’s activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy."

Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020.1 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.2 Approximately 80 percent of people do not respond to PD-1 or PD-L1 inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease.3

About the EV-301 Trial
The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate PADCEV versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival of participants treated with PADCEV compared to those treated with chemotherapy. Secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters.

For more information about the EV-301 clinical trial, please visit www.clinicaltrials.gov.

About PADCEV (enfortumab vedotin-ejfv)
PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA’s Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.4

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.4,5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seattle Genetics.

PADCEV Important Safety Information

Warnings and Precautions

Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.
Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.
Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients for skin reactions. Consider appropriate treatment, such as topical corticosteroids and antihistamines for skin reactions, as clinically indicated. For severe (Grade 3) skin reactions, withhold PADCEV until improvement or resolution and administer appropriate medical treatment. Permanently discontinue PADCEV in patients that develop Grade 4 or recurrent Grade 3 skin reactions.
Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.
Adverse Reactions
Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab Abnormalities
In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

Drug Interactions

Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.
Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.
Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

On September 18, 2020 Incyte (Nasdaq:INCY) reported results from its Phase 2 POD1UM-202 trial evaluating retifanlimab, a PD-1 inhibitor, in previously treated patients with advanced squamous cell carcinoma of the anal canal (SCAC) who have progressed following standard platinum-based chemotherapy (Press release, Incyte, SEP 18, 2020, View Source [SID1234565342]). The trial enrolled 94 patients, including those with well-controlled human immunodeficiency virus (HIV) infection (10%).

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Retifanlimab monotherapy resulted in a confirmed objective response rate (ORR) of 14% as determined by independent central review (ICR) using RECIST v1.1. Responses were observed regardless of PD-L1 status, presence of liver metastases, age or HIV+ status. Retifanlimab was generally well-tolerated with a safety profile as expected of a PD-1 inhibitor and no loss of HIV infection control.

Key findings from POD1UM-202:

*Confirmed responses as determined by independent central review (ICR) using RECIST v1.1.

ORR: objective response rate; CI: confidence interval; OR: objective response; CR: complete response; PR: partial response; SD: stable disease; DCR: disease control rate; DOR: duration of response; PFS: progression-free survival; OS: overall survival; NE: not estimable.

"The results from the POD1UM-202 trial highlight the potential of retifanlimab to provide a meaningful treatment for patients with SCAC who have progressed following standard platinum-based chemotherapy and therefore have a very poor prognosis," said Lance Leopold, M.D., Group Vice President, Immuno-Oncology Clinical Development, Incyte. "These data are especially important because this trial enrolled HIV+ patients who are at the greatest risk of developing SCAC and are typically systematically excluded from oncology clinical trials."

These results are available on-demand as part of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2020 Virtual Congress mini-oral sessions beginning at 9:00 am CEST on September 18th, 2020; Presentation #LBA42.

"SCAC is a rare cancer with increasing incidence, including in patients who are HIV+, and represents a strong unmet medical need," said Sheela Rao, M.D., Consultant Medical Oncologist, The Royal Marsden NHS Foundation Trust. "Data from the POD1UM-202 trial are encouraging and support further investigation of the potential of retifanlimab to become a much needed treatment option for patients with SCAC."

SCAC is associated with human papillomavirus (HPV) and HIV infections and accounts for almost 3% of digestive system cancers.1 Patients with metastatic SCAC have a poor 5-year survival and there are no standard treatments for patients who have progressed after first-line chemotherapy treatment.2

POD1UM-303/InterAACT 2 (NCT04472429), a Phase 3 trial of retifanlimab in combination with carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic SCAC is now open and recruiting patients.

About POD1UM

The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-202, POD1UM-303 and several other Phase 1, 2 and 3 studies for patients with solid tumors including squamous cell carcinoma of the anal canal (SCAC), microsatellite instability-high endometrial cancer, Merkel cell carcinoma and non-small cell lung cancer, among others.

About POD1UM-202

POD1UM-202 (NCT03597295) is an open-label, single-arm, multicenter, Phase 2 study evaluating retifanlimab in patients with squamous cell carcinoma of the anal canal (SCAC) who have progressed following platinum-based chemotherapy. Retifanlimab 500 mg is administered intravenously every 4 weeks.

The primary endpoint is objective response rate (ORR) as determined by independent central review using RECIST v1.1. Secondary endpoints include additional measures of clinical benefit ‒ duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS); safety and pharmacokinetics.

For more information about the study, please visit View Source

About POD1UM-303/InterAACT 2

POD1UM-303/InterAACT 2 (NCT004472429) is a Phase 3, randomized, multicenter, double-blind study evaluating retifanlimab or placebo plus carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).

Adult patients, including those with well-controlled HIV infection, who have not been previously treated with systemic chemotherapy will be randomized to receive retifanlimab or placebo with standard therapy of carboplatin and paclitaxel.

The primary endpoint is progression-free survival (PFS) as determined by blinded independent central review using RECIST v1.1. Key secondary endpoint is overall survival (OS). Other secondary endpoints include: objective response rate (ORR), duration of response (DOR), disease control rate (DCR), safety and pharmacokinetics.

For more information about the study, please visit View Source

About Retifanlimab

Retifanlimab (formerly INCMGA0012), an investigational anti-PD1 antibody, is currently under evaluation in registration-directed trials as a monotherapy for patients with microsatellite instability-high endometrial cancer, Merkel cell carcinoma and squamous cell carcinoma of the anal canal (SCAC); and in combination with platinum-based chemotherapy for patients with non-small cell lung cancer and SCAC.

Retifanlimab has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of anal cancer.

In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab. In 2019, Incyte and Zai Lab announced a collaboration and license agreement for the development and commercialization of retifanlimab in Greater China.

On September 18, 2020 Reference is made to the stock exchange announcement by Targovax ASA (OSE:TRVX) ("Targovax" or the "Company") on 31 August 2020, regarding the board of directors’ resolution to increase the share capital of the Company in connection with the settlement of restricted stock units (Press release, Targovax, SEP 18, 2020, View Source [SID1234565341]).

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The share capital increase has today been registered with the Norwegian Register of Business Enterprises (Nw. Foretaksregisteret). The Company’s new share capital is NOK 7,617,576.40, divided into 76,175,764 shares, each with a par value of NOK 0.10.