A Study to Evaluate INCB099280 in Participants With Advanced Cutaneous Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This study is being conducted to determine the safety, tolerability, and preliminary efficacy of INCB099280 in participants with advanced Cutaneous Squamous Cell Carcinoma.

Official Title
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A Phase 2 Study Evaluating INCB099280 in Participants With Advanced Squamous Cell Carcinoma

Conditions
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Cutaneous Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: INCB099280


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological diagnosis of cSCC. Previously untreated or recurrent locally advanced (without nodal metastases) or metastatic (distant or regional metastasis) cSCC not amenable to curative surgery and/or radiotherapy. Measurable disease based on either radiographic imaging per RECIST 1.1 or WHO criteria. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Life expectancy > 3 months. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Known history of an additional malignancy. Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease. Toxicity from prior therapy that has not recovered. 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). Received thoracic radiation within 6 months of the first dose of study treatment. 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 allogeneic 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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All

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study consists of 2 parts. In Part 1, participants with metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC will be randomized 1:1:1 to INCB099280 Dose 1, Dose 2, or Dose 3. In Part 2, one dose level identified from Part 1 will be expanded to enroll additional participants with metastatic cSCC and locally advanced cSCC.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: INCB099280 Dose 1<br>Participants will receive INCB099280 dose 1 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description.<br>|
| Experimental: Part 1: INCB099280 Dose 2<br>Participants will receive INCB099280 dose 2 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description.<br>|
| Experimental: Part 1: INCB099280 Dose 3<br>Participants will receive INCB099280 dose 3 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description.<br>|
| Experimental: Part 2: INCB099280 Dose selected from Part 1<br>Participants will receive INCB099280 dose selected from Part 1 twice daily (BID) for up to 2 years. | Drug: INCB099280<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 |
| --- | --- | --- |
| Objective response rate (ORR) | Defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by the blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or composite criteria for metastatic cSCC and per World Health Organization (WHO) criteria for locally advanced cSCC. | Up to 2 years | 
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Defined as any Adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after the last dose of study drug or until the start of new anticancer therapy, whichever occurs first. | Up to 2 years 3 months | 
| Number of participants with TEAEs leading to dose modification or discontinuation | Number of participants with TEAEs leading to dose modification or discontinuation. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Defined as the percentage of participants with the best overall response of CR or PR, or stable disease (SD), after a minimum of 15 weeks following the initiation of study treatment as determined by the BICR per RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC. | Up to 2 years | 
| Duration Of Response (DOR) | Defined as the time from the earliest date of confirmed CR or PR to the earliest date of disease progression, as determined by the BICR according to RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC or death due to any cause if occurring sooner than progression. | Up to 2 years | 
| Time to Response (TTR) | Defined as the time from the date of first dose to the earliest date of confirmed CR or PR as determined by the BICR according to RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC. | Up to 2 years | 
| Progression-free survival (PFS) | Defined as the time from the date of first dose to the earliest date of disease progression as determined by the BICR according to RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC or death due to any cause if occurring sooner than progression. | Up to 2 years | 
| Overall Survival (OS) | Defined as the time from the date of first dose to death due to any cause. | Up to 2 years | 
| INCB099280 pharmacokinetic (PK) in Plasma | INCB099280 concentration in plasma | Pre dose and 1, 2 and 6 hours post dose on Cycle 1 Day 1 and Cycle 2 Day 1. Pre dose every other cycle until Cycle 11 Day 1 (Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1 and Cycle 11 Day 1) (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic cutaneous squamous cell carcinoma, Cutaneous Squamous Cell Carcinoma, Anti-PD-L1 antibody, Locally advanced cutaneous squamous cell carcinoma