A study exploring the safety, tolerability, and efficacy of INCAGN01876 in combination with immune therapies in subjects with advanced or metastatic malignancies.

Phase 1

Active, not recruiting

Conditions: Ph1: adv. or metast. cervical cancer, endometrial cancer, gastric cancer, hepatocellular carcinoma, melanoma, 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, urothelial carcinoma or others.Ph2: adv. or metast. cervical cancer, gastric cancer, SCCHN, PD-1 refractory SCCHN, and PD-1 or PD-L1 relapsed melanoma
MedDRA version: 21.1Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: LLTClassification code 10064025Term: Merkel cell carcinomaSystem Organ Class: 10029104 - Neoplasms ben
MedDRA version: 21.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10027407Term: Mesothelioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-004989-25-BE

Lead Sponsor: Incyte Biosciences International Sàrl

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: 450

Inclusion Criteria

Note: Due to space limitation in this window, a restricted set of subject inclusion criteria are presented below. The complete and detailed criteria are listed in the protocol.
• 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 (excluding uveal melanoma), 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 cervical cancer, gastric cancer (including stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN, or PD-1 or PD-L1 relapsed melanoma.
- For subjects with cervical cancer: should have histologically confirmed squamous cell carcinoma of the cervix.
- For subjects with gastric cancer: adenocarcinoma of the stomach, esophagus, or GEJ.
- For subjects with SCCHN: histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. 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 and EBV tumor 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 (Stage 2 only): Should have progressive disease per RECIST v1.1 during or within 6 months after treatment with a platinum-containing regimen. The platinum based therapy must be the last therapy the subject received before enrollment.
-For subjects with PD-1 refractory SCCHN: histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
Note: Should consent to have tumor evaluated for HPV and EBV status of the tumor(per local institutional testing), or have documentation of HPV and EBV tumor status.
Note: PD-1 refractory SCCHN is defined as meeting all of the following criteria:
i. Progressive disease per RECIST v1.1 as best overall response to treatment with an anti PD-1 containing regimen that is confirmed at least 4 weeks (no less than28 days) later.
ii. Progressive disease should be at least 12 weeks from first dose of anti–PD-1 therapy and confirmed 4 weeks (no less than 28 days) later.
iii. Should have received prior treatment with anti-PD-1 therapy for advanced or metastatic disease.
iv. Should have received at least 2 doses of a prior anti–PD-1 containing regimen.
v. The PD-1 therapy must be the last therapy the subject received before enrollment.
- Tumor biopsy sample collection
i. For subjects in the biopsy cohort: willingness to undergo pretreatment and on treatment tumor biopsies (core or excisional). Must have cervical cancer, endometrial cancer, gastric cancer (including stomach, esophageal and GEJ), SCCHN, PD-1 refractory SCCHN, PD-1 or P

Exclusion Criteria

• 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 determin

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

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