INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC)

Official Title
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A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

Conditions
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Ovarian Cancer, Bladder Cancer, Non Small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Cancer, Castration Resistant Prostate Cancer, Colorectal Cancer, Gastric/ Gastroesophageal Junction, Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma, Squamous Carcinoma of the Anal Canal

Intervention / Treatment
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* Drug: INCB106385
* Drug: INCMGA00012


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to comprehend and willingness to sign an ICF. Willing and able to conform to and comply with all Protocol requirements. Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian cancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment with available therapies (including anti PD-(L)1 therapy (if applicable). Willingness to undergo pre- and on-treatment tumor biopsy. Have CD8 T-cell-positive tumors. Presence of measurable disease according to RECIST v1.1. ECOG performance status 0 to 1. Life expectancy > 12 weeks. Willingness to avoid pregnancy or fathering children based. Acceptable laboratory parameters Exclusion Criteria: Clinically significant cardiac disease. Known or active CNS metastases and/or carcinomatous meningitis. Active or inactive autoimmune disease or syndrome that required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease.. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment. Known additional malignancy that is progressing or requires active treatment,or history of other malignancy within 2 years of the first dose of study treatment. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment. Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended, or any immune-related toxicity requiring intensive or prolonged immunosuppression to manage. Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. Any prior radiation therapy within 28 days before the first dose of study treatment. Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. Concomitant treatment with strong CYP3A4 inhibitors or inducers. Receipt of a live vaccine within 30 days of the first dose of study treatment. Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of the first dose of study treatment. Evidence of HBV or HCV infection or risk of reactivation. Known history of HIV (HIV 1/2 antibodies). History of organ transplant, including allogeneic stem-cell transplantation. Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components. Presence of a gastrointestinal condition that may affect drug absorption. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study. Any condition that would, in the investigator's judgment, interfere with full participation in the study,pose a significant risk to the participant; or interfere with interpretation of study data

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A (TGA) - INCB106385<br>In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE. | Drug: INCB106385<br>* INCB106385 will be administered orally QD<br>|
| Experimental: Treatment Group B (TGB) - INCB106385+INCMGA00012<br>In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE. | Drug: INCB106385<br>* INCB106385 will be administered orally QD<br>Drug: INCMGA00012<br>* INCMGA0012 will be administered IV once every 4 weeks (Q4W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events (TEAE) | 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 last dose of study drug. | Up to Approximately 28 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of INCB106385 as a single agent or in combination with INCMGA00012 | Maximum observed plasma concentration. | Up to 6 months | 
| Tmax of INCB106385 as a single agent or in combination with INCMGA00012 | Time to maximum plasma concentration | Up to 6 months | 
| Cmin of INCB106385 as a single agent or in combination with INCMGA00012 | Minimum observed plasma concentration over the dose interval | Up to 6 months | 
| AUC of INCB106385 as a single agent or in combination with INCMGA00012 | Area under the plasma concentration-time curve | Up to 6 months | 
| CL/F of INCB106385 as a single agent or in combination with INCMGA00012 | Apparent oral dose clearance | Up to 6 months | 
| Objective Response Rate (ORR) | Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1. | Up to approximately 24 months | 
| Disease Control Rate | Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1. | Up to approximately 24 months | 
| Duration Of Response (DOR) | Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression. | Up to approximately 24 months | 
| Change in tumoral gene expression | Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline | Predose and Week 5-6 | 
| Change in immune cell activation in tumors | Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline | Predose and Week 5-6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INCB106385, Advanced Solid Tumors, PD-1