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

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)

This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of etigilimab in combination with nivolumab in participants with locally advanced or metastatic solid tumors. Participants will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 milligrams [mg] every 2 weeks).

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Solid Tumor, Adult
• Intervention / Treatment: Drug: Nivolumab; Drug: Etigilimab

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 participants with locally advanced or metastatic solid tumors. Participants 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. Participants may continue to receive treatment beyond documented Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) or disease progression. Participants who are both checkpoint inhibitor (CPI) naive as well as participants 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 Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Royal Marsden
  • London, United Kingdom
    • Sarah Cannon UK
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mereo Investigator Site
  • California
    • Greenbrae, California, United States, 94904
      • Mereo Investigator Site
    • Los Angeles, California, United States, 90025
      • Mereo Investigator Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mereo Investigator Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Mereo Investigator Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Mereo Investigator Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mereo Investigator Site
  • New York
    • New York, New York, United States, 10065
      • Mereo Investigator Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Mereo Investigator Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Mereo Investigator Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Mereo Investigator Site
  • Texas
    • Houston, Texas, United States, 77030
      • Mereo Investigator Site
  • Utah
    • West Valley City, Utah, United States, 84119
      • Mereo Investigator Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Mereo Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Eastern Cooperative Oncology Group (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
• Participants with active, known or suspected autoimmune diseases
• Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibodies
• History of any Grade 3 or 4 immune-related adverse event (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 human immunodeficiency virus (HIV), hepatitis B, hepatitis C
• Medical illness or abnormal laboratory finding that would, in the Study Investigator's judgement, increase the risk to the participant associated with participation in the study
• Pregnancy in female participants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive; Participants with endometrial cancer CPI (programmed death-1 [PD-1]/ programmed death ligand-1 [PD-L1]) naive will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort B: Head and Neck Squamous Cell Carcinoma; Participants with head and neck cell carcinoma will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort C: Cervical Carcinoma; Participants with cervical carcinoma will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort D (Recurrent Advanced and/or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma); Participants with recurrent advanced and/or metastatic gastric or gastroesophageal junction adenocarcinoma will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort E: TMB-H + MSS Solid Tumors; Participants with tumour mutational burden-high (TMB-H) and microsatellite stable (MSS) solid tumors will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell); Participants with rare tumors (sarcoma, uveal melanoma, and germ cell) will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated); Participants with endometrial cancer (PD-1/PD-L1 treated) will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313
Experimental: Cohort H: Ovarian Cancer; Participants with ovarian cancer will receive etigilimab in combination with nivolumab every 2 weeks and will continue treatment until protocol-defined discontinuation criteria are met.	Drug: Nivolumab; IV infusion of nivolumab every 2 weeks; Other Names: Opdivo; Drug: Etigilimab; IV infusion of IV etigilimab every 2 weeks; Other Names: MPH313

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)	The ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions	TEAEs were defined as adverse events (AEs) with an onset date on or after the date of first administration of study drug up to 100 days after the last dose of study drug and before starting any subsequent cancer treatment. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESIs were defined as events (serious or non-serious) which were of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor might be appropriate. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days)
Disease Control Rate (DCR) as Assessed Based on RECIST v1.1	The DCR was defined as the percentage of participants who achieved CR, PR, and stable disease (SD). CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; and no new lesions.	From first dose of study drug until the date of first BOR (CR, PR, or SD) (maximum exposure: 638 days)
Duration of Response (DoR) as Assessed Based on RECIST v1.1	The DoR was defined as the time, in days, from the first of the 2 assessments required for confirmed PR or CR to the time of the progressive disease (PD) or death due to underlying cancer. CR: Disappearance of all target or non-target lesions and normalization of tumor marker level. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression.	From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (maximum exposure: 638 days)
Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1	The DoSD was defined as the time, in days, from the first date of treatment until the first date at which PD was experienced or the participant died due to underlying cancer. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of the existing non-target lesions. The appearance of one or more new lesions was also considered progression.	From first dose of study drug until the date of first overall response of PD or date of death due to underlying cancer (up to a maximum of 680 days)
Serum Concentrations of Etigilimab		Pre-infusion and 15 minutes post-infusion on Cycle 1 Day 1 and Cycle 4 Day 43
Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab		From first dose of study drug until 100 days after the last dose of study drug or the initiation of any subsequent cancer treatment, whichever occurs first (maximum exposure: 638 days)

Collaborators and Investigators

• Sponsor: Mereo BioPharma
• Collaborators: ICON Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: nivolumab; Opdivo; etigilimab; anti-TIGIT antibody; MPH313; ACTIVATE
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: MPH313-1-02; 2020-004222-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No