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

Sponsor

Mereo BioPharma (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04761198

Collaborator

ICON Clinical Research (Industry)

125

Enrollment

Locations

Arms

27.2

Anticipated Duration (Months)

7.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult Advanced Solid Tumor Metastatic Solid Tumor	Drug: Etigilimab dosing Drug: Nivolumab	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Basket studyBasket study

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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)

Actual Study Start Date :

Mar 23, 2021

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [Approximately 24 months.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mereo Investigator Site	Phoenix	Arizona	United States	85054
2	Mereo Investigator Site	Greenbrae	California	United States	94904
3	Mereo Investigator Site	Los Angeles	California	United States	90025
4	Mereo Investigator Site	Jacksonville	Florida	United States	32224
5	Mereo Investigator Site	Boston	Massachusetts	United States	02215
6	Mereo Investigator Site	Ann Arbor	Michigan	United States	48109
7	Mereo Investigator Site	Rochester	Minnesota	United States	55905
8	Mereo Investigator Site	New York	New York	United States	10065
9	Mereo Investigator Site	Durham	North Carolina	United States	27710
10	Mereo Investigator Site	Oklahoma City	Oklahoma	United States	73104
11	Mereo Investigator Site	Nashville	Tennessee	United States	37203
12	Mereo Investigator Site	Houston	Texas	United States	77030
13	Mereo Investigator Site	West Valley City	Utah	United States	84119
14	Mereo Investigator Site	Fairfax	Virginia	United States	22031
15	Royal Marsden	London		United Kingdom
16	Sarah Cannon UK	London		United Kingdom