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)
Overview
- Phase
- Phase 1
- Intervention
- Etigilimab
- Conditions
- Solid Tumor, Adult
- Sponsor
- Mereo BioPharma
- Enrollment
- 76
- Locations
- 3
- Primary Endpoint
- Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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).
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
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.
Intervention: Etigilimab
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.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
Time Frame: From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days)
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.
Secondary Outcomes
- Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions(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(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(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(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))