A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The primary goal of this Phase 1 study is to characterize the safety and tolerability of INCMGA00012 and establish the maximum tolerated dose (MTD) of INCMGA00012 administered on either every two week or every four week schedules of administration among patients with solid tumors. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of INCMGA00012 will also be assessed. The purpose of Amendment 5 is to obtain additional safety experience at the newly defined recommended Phase 2 dose of 500 mg every 4 weeks in patients with endometrial cancer, specifically either microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Additionally, every 3 week (Q3W) flat-dosing will be studied in an additional tumor agnostic cohort.

Detailed Description
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This study is a Phase 1, open-label, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary anti-tumor activity of INCMGA00012 administered IV every 2, 3, or 4 weeks in patients with relapsed/refractory, unresectable locally advanced or metastatic solid tumors. In the initial phase of the study, two dose schedules will be assessed in dose escalation, once every two weeks and once every four weeks administration of single agent INCMGA00012. Following the establishment of an MTD, additional patients will enroll in expansion cohorts of specific tumor types and/or INCMGA00012 dose. The Cohort Expansion Phase will include tumor-specific cohorts, consisting of patients with endometrial cancer (unselected [up to n = 35] and MSI-H or dMMR [up to n = 70]), cervical cancer (up to n = 35), sarcoma (up to n = 35), non-small cell lung cancer (NSCLC) (up to n = 35), and 3 cohorts of any tumor histology (tumor-agnostic) (up to n = 15) who will receive flat dosing: 1 cohort treated with INCMGA00012 500 mg Q4W, 1 cohort with INCMGA00012 750 mg Q4W, and 1 cohort treated with INCMGA00012 375 mg Q3W.

Official Title
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A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of INCMGA00012 in Patients With Advanced Solid Tumors

Conditions
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Locally Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven, locally advanced unresectable or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined. Patients enrolled to Cohort H (endometrial cancer 500 mg Q4W) must have MSI-H or dMMR endometrial cancer, as determined by a local laboratory using IHC or PCR methods and must also have tissue (fresh or archival) available for central confirmation of diagnosis Expansion cohort(s): Progression during or following at least 1, and up to 5, previous systemic therapies, consistent with the standard of care for the specific tumor type. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy ≥ 12 weeks Measurable disease Acceptable laboratory parameters Exclusion Criteria: Symptomatic central nervous system (CNS) metastases. For Cohort Expansion, patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) are not eligible for this study. Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 4 weeks prior to the initiation of study drug administration. Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration. Clinically significant cardiovascular disease Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation. Presence of active pneumonitis or history of non-infectious pneumonitis. Clinically significant gastrointestinal disorders Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than one week prior to the initiation of study drug Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome. Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR) Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed Dementia or altered mental status that would preclude understanding and rendering of informed consent

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: Dose Escalation-Q2W<br>INCMGA00012 treatment once every 2 weeks. | Drug: retifanlimab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: INCMGA0012;|
| Experimental: Dose Escalation- Q3W<br>INCMGA00012 treatment once every 3 weeks. | Drug: retifanlimab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: INCMGA0012;|
| Experimental: Dose Escalation- Q4W<br>INCMGA00012 treatment once every 4 weeks. | Drug: retifanlimab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: INCMGA0012;|
| Experimental: Expansion Cohort<br>INCMGA00012 treatment for locally advanced or metastatic solid tumors. | Drug: retifanlimab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: INCMGA0012;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 | Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. | 24 months | 
| MTD | Maximum Tolerated Dose of INCMGA00012 | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area Under the Plasma Concentration versus Time Curve of INCMGA00012 | 24 months | 
| Cmax | Maximum Plasma Concentration of INCMGA00012 | 24 months | 
| Tmax | Time to reach maximum (peak) plasma concentration of INCMGA00012 | 24 months | 
| Ctrough | Trough plasma concentration of INCMGA00012 | 24 months | 
| Total body clearance of the drug from plasma (CL) of INCMGA00012 |  | 24 months | 
| Vss | Apparent volume of distribution at steady state of INCMGA00012 | 24 months | 
| t1/2 | Terminal half-life of INCMGA00012 | 24 months | 
| ADA | Percent of patients with anti-drug antibody | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors, Metastatic cancer