A Study of Etigilimab and Nivolumab in Subjects With Locally Advanced or Metastatic Tumors.

Study Overview
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Brief Summary
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This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab in combination with nivolumab in subjects with locally advanced or metastatic solid tumors. Subjects will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 mg every 2 weeks).

Detailed Description
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This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab in combination with nivolumab in subjects with locally advanced or metastatic solid tumors. Subjects will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 mg every 2 weeks) and will continue until either unacceptable toxicity or disease progression. Subjects may continue to receive treatment beyond documented RECIST 1.1 or disease progression. Subjects who are both CPI (checkpoint inhibitor) naïve as well as subjects who have received or progressed following a CPI will be eligible and include the following tumor types: head and neck squamous cell carcinoma (HNSCC), cervical carcinoma, gastric or gastroesophageal carcinoma, endometrial carcinoma, tumor mutation burden high (TMB-H), select rare tumors and ovarian carcinoma.

Official Title
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A Phase 1b/2 Open-Label Study of the Efficacy and Safety of Etigilimab (MPH313) Administered in Combination With Nivolumab to Subjects With Locally Advanced or Metastatic Solid Tumors (ACTIVATE)

Conditions
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Solid Tumor, Adult, Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: Etigilimab dosing
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of a relevant tumor type as per the study protocol and not candidates for curative surgery or radiation therapy Available tumor tissue (archival or newly obtained core or excisional biopsy) Adequate hematologic and end organ function as measured by laboratory screening panel in the 14 days prior to treatment Life expectancy greater than 12 weeks. ECOG performance status of 0 to 1 Adequate contraception for women of childbearing potential Pre-specified wash-out of prior anti-PD1/PDL-1 therapy Exclusion Criteria: Concurrent active malignancy Major surgery within 4 weeks of treatment Subjects with active, known or suspected autoimmune diseases Prior treatment with CD137 agonists, anti-CTLA-4 and anti-TIGIT antibodies History of any Grade 3 or 4 immune-related AE toxicity from prior immunotherapy that resulted in treatment discontinuation History of immune-related adverse events that lead to discontinuation of anti-PD-1 or PDL-1 therapy Active infections of HIV, hepatitis B, hepatitis C Medical illness or abnormal laboratory finding that would, in the Study Investigator's judgement, increase the risk to the subject associated with participation in the study Pregnancy in female subjects

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Basket study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Squamous cell carcinoma of the head and neck<br>Advanced and/or recurrent or metastatic squamous cell carcinoma of the head and neck | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Cervical cancer on or after chemotherapy<br>Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Gastric or gastroesophageal junction adenocarcinoma<br>Recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Endometrial carcinoma post-platinum <3L treatment<br>Advanced and/or metastatic endometrial carcinoma | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Tumor burden high (TMB-H) and microsatellite stable (MSS) solid tumors<br>Advanced or metastatic tumor mutational burden-high (TMB-H) | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Rare disease with high prevalence of TIGIT expression<br>Select rare tumors | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Ovarian cancer<br>Recurrent high grade serous and endometrioid ovarian cancer, fallopian tube cancer or primary peritoneal cancer following front-line platinum-based therapy | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|
| Experimental: Endometrial carcinoma post standard of care therapy<br>Advanced and/or metastatic endometrial carcinoma | Drug: Etigilimab dosing<br>* IV infusion of IV etigilimab every 2 weeks<br>* Other names: MPH313;Drug: Nivolumab<br>* IV infusion of nivolumab every 2 weeks<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The ORR is the proportion of subjects whose best response rate (BOR) is confirmed CR or confirmed PR radiographically according to RECISTv1.1. Where BOR is defined as the best investigator-assessed confirmed response during the time period. | Approximately 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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etigilimab, nivolumab, anti-TIGIT antibody, MPH313, Opdivo, ACTIVATE