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

Mereo BioPharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Solid Tumor, Adult; Advanced Solid Tumor; Metastatic Solid Tumor

Treatments: Drug: Nivolumab; Drug: Etigilimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04761198

MPH313-1-02

2020-004222-37 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.
• 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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76 participants in 8 patient groups

Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort B: Head and Neck Squamous Cell Carcinoma

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort C: Cervical Carcinoma

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort D (Recurrent Advanced and/or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma)

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort E: TMB-H + MSS Solid Tumors

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell)

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated)

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab

Cohort H: Ovarian Cancer

Experimental group

Description:

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.

Treatment:

Drug: Etigilimab

Drug: Nivolumab