A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is being conducted to evaluate the safety and tolerability of INCB099280 in combination with axitinib and to assess the antitumor activity of INCB099280 in combination with axitinib. This study will only be open in the UK and EU.

Official Title
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A Phase 1/2 Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: INCB099280
* Drug: axitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered non-amenable to surgery or other curative treatments or procedures. Must have disease progression on or after treatment with at least one prior systemic chemotherapy. Eastern Cooperative Oncology Group performance status score of 0 or 1. Life expectancy > 12 weeks. Willingness to avoid pregnancy. Exclusion Criteria: Known additional malignancy that is progressing or requires active treatment. Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease. Toxicity from prior therapy that has not recovered to protocol-defined limits. Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell). Prior therapy with antiangiogenic small-molecule TKIs targeting the VEGF pathway Participation in another interventional clinical study while receiving INCB099280. Impaired cardiac function or clinically significant cardiac disease. History or evidence of interstitial lung disease including noninfectious pneumonitis. Presence of gastrointestinal conditions that may affect drug absorption. Any autoimmune disease requiring systemic treatment in the past 5 years. Diagnosis of primary immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent. Active infection requiring systemic therapy. History of organ transplantation, including stem cell transplantation. Receipt of systemic antibiotics within 28 days of first dose of study treatment. Probiotic usage is prohibited during screening and throughout the study treatment period. Received a live vaccine within 28 days of the planned start of study drug. Laboratory values outside the Protocol-defined ranges. Inadequate organ function. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study consists of 2 parts. In the Part 1 dose-escalation, participants will be enrolled in up to 6 dose levels of INCB099280 administered in combination with axitinib. In the Part 2 dose expansion, participants will be enrolled into 1 of 2 disease-specific cohorts at the dose(s) identified in Part 1.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Up to 6 doses of INCB099280 administered twice daily (BID) in combination with axitinib BID will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study. | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>Drug: axitinib<br>* Administered as specified in the treatment arm description<br>|
| Experimental: Part 2: Dose Expansion<br>On completion of Part 1, participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort 1: Adults with clear-cell gynecological cancers with at least 50% clear-cell histology whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. Cohort 2: Adults with rare histological subtype epithelial cancers of the gynecological tract whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. One or two doses may be selected from Part 1 for each cohort in the Part 2 Expansion. | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>Drug: axitinib<br>* Administered as specified in the treatment arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with Dose Limiting Toxicities (DLTs) | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. | Up to 21 days | 
| Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs) | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 2 years and 90 days | 
| Part 1: Number of participants with TEAEs leading to dose modification | Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug). | Up to 2 years | 
| Part 2: Objective response rate (ORR) | Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Number of participants with Treatment-emergent Adverse Events (TEAEs) | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 2 years and 90 days | 
| Part 2: Number of participants with TEAEs leading to dose modification | Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug). | Up to 2 years | 
| Part 1: Objective response rate (ORR) | Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Up to 2 years | 
| Disease Control Rate (DCR) | Defined as the best overall response of CR, PR, or stable disease (SD) of at least 11 weeks from the start of treatment by investigator assessment per RECIST v1.1. | Up to 2 years | 
| Duration of Response (DOR) | Defined as the time from the first CR or PR until disease progression by investigator assessment per RECIST v1.1 or death from any cause, whichever occurs earlier. | Up to 2 years | 
| INCB099280 and axitinib plasma concentrations. | PK parameters will be calculated from the blood plasma concentrations of INCB099280 and axitinib using standard noncompartmental (model independent) PK methods. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gynecologic tract cancer, ovarian cancer, primary peritoneum cancer, fallopian tube cancer, uterine cancer, cervical cancer, vulvar cancer, vaginal cancer, clear cell histology, mucinous adenocarcinoma, carcinosarcoma, serous adenocarcinoma, neuroendocrine histology, small cell histology, small-molecule pdl1 inhibitor, tyrosine kinase inhibitor, combination therapy