A study exploring the safety, tolerability, and efficacy of INCAGN01876 in combination with immune therapies in subjects with advanced or metastatic malignancies.
- Conditions
- Phase 1: advanced or metastatic cervical cancer, endometrial cancer, gastric cancer, hepatocellular carcinoma, melanoma (mucosal or cutaneous), Merkel cell carcinoma, mesothelioma, MSI-H colorectal cancer, non–small cell lung cancer, ovarian cancer, squamous cell carcinoma of the head and neck (SCCHN), small cell lung cancer, renal cell carcinoma, triple-negative breast cancer, and urothelial carcinoma (or others). Phase 2: advanced or metastatic endometrial cancer, gastric cancer, and SCCHNMedDRA version: 20.0Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10027407Term: Mesothelioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000017553MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 100000018529MedDRA version: 20.0Level: LLTClassification code 10064025Term: Merkel cell carcinomaSystem Organ Class: 100000018548MedDRA version: 20.0Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, maligna
- Registration Number
- EUCTR2016-004989-25-ES
- Lead Sponsor
- Incyte Biosciences International Sàrl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 145
• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Phase 1: Subjects with advanced or metastatic cervical cancer, endometrial cancer, gastric cancer (including stomach, esophageal, and GEJ), HCC, melanoma (mucosal or cutaneous), Merkel cell carcinoma, mesothelioma, MSI-H CRC, NSCLC, ovarian cancer, SCCHN, SCLC, RCC, TNBC, and urothelial carcinoma (or alternative tumor types with medical monitor approval).
• Phase 1: Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
• Phase 2: Subjects with advanced or metastatic endometrial cancer, gastric cancer (including stomach, esophageal, and GEJ), and SCCHN.
- For subjects with endometrial cancer: should have documented MSI status (eg, MSI-H, MSI-low, microsatellite stable), or consent to local institutional MSI testing during the screening period. Note: Should have received only 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy). Adjuvant regimens given within 6 months of screening would be counted as first-line therapy. Note: Prior therapy should not have included an immune therapy (eg, anti–cytotoxic T-lymphocyte–associated protein 4 [CTLA-4], anti–programmed cell death protein 1 (PD-1), anti–programmed cell death protein ligand 1 (PD-L1), indoleamine 2,3-dioxygenase [IDO] inhibitors, tumor necrosis factor super family (TNFSF) agonists, or other antibodies or drugs specifically targeting T-cell costimulation or checkpoint pathways, etc). Note: May have received prior hormonal and/or biological therapy concurrent with or in addition to prior systemic chemotherapy.
- For subjects with gastric cancer: adenocarcinoma of the stomach, esophagus, or GEJ. Note: Should have received only 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy). Adjuvant regimens given within 6 months of screening would be counted as first-line therapy. Note: Prior therapy should not have included an immune therapy (eg, anti–CTLA-4, anti–PD-1, anti–PD-L1, IDO inhibitors, TNFSF agonists, or other antibodies or drugs specifically targeting T-cell costimulation or checkpoint pathways, etc). Note: HER-2/neu status known and subjects with HER2/neu positive tumors should have documented disease progression on or after treatment containing trastuzumab or other HER2/neu-targeted therapy.
- For subjects with SCCHN: histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Note: Subjects with tumors that are adjacent to or invade major blood vessels, as shown unequivocally by imaging studies are not eligible for participation. Note: Should consent to have tumor evaluated for HPV and Epstein-Barr virus (EBV) status of the tumor (per local institutional testing), or have documentation of HPV or EBV status. Note: Should have received only 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy). Adjuvant regimens given within 6 months of screening would be counted as first-line therapy. Prior chemotherapy regimen should have been a platinum-containing regimen. Note: Prior therapy should not have included an immune the
• Laboratory and medical history parameters not within the Protocol-defined range.
- Absolute neutrophil count < 1.0 × 10^9/L
- Platelets < 75 × 10^9/L
- Hemoglobin < 9 g/dL or < 5.6 mmol/L
- Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR measured or calculated creatinine clearance < 50 mL/min for subjects with creatinine levels > 1.5 × ULN.
- Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase = 2.5 × ULN.
- Total bilirubin = 1.2 × ULN unless conjugated bilirubin = ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
- International normalized ratio, prothrombin time, or activated partial thromboplastin time > 1.5 × ULN.
• Prior treatment with any TNFSF agonist (eg, glucocorticoid-induced tumor necrosis factor receptor [GITR], OX40, 4-1BB/CD137, CD27, etc), for any indication.
• Transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors within 14 days before study Day 1.
• Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:
- = 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Note: Subjects must not have had radiation pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non–central nervous system (CNS) disease with medical monitor approval. Note: Bisphosphonates and denosumab are permitted concomitant medications.
- = 28 days for prior immune therapy or persistence of active cellular therapy (ie, chimeric antigen receptor T-cell therapy; other cellular therapies must be discussed with medical monitor to determine eligibility).
- = 28 days for a prior monoclonal antibody used for anticancer therapy with the exception of denosumab.
- = 7 days for immune-suppressive–based treatment for any reason. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted. Note: Must not require chronic use of corticosteroids. The use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor.
- = 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.
• Has not recovered to = Grade 1 from toxic effects of prior therapy (including prior immune therapy) and/or complications from prior surgical intervention before starting therapy Note: Subjects with stable chronic conditions (= Grade 2) not expected to resolve (such as neuropathy and alopecia) are exceptions and may enroll. Note: Subjects with a history of any grade immune-related ocular AE (eg, episcleritis, scleritis, uveitis) will be excluded. Note: Subjects with a history of a Grade 3 or higher immune-related AE from prior immunotherapies are excluded from the dose escalation portion of the study.
• Active autoimmune disease that required systemic treatment in the past (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Subjects who have not required systemic treatment in the past 2 years should discuss their case with medical monitor to determine eligibilit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method