Clinical trial NCT04761198: A Study of Etigilimab and Nivolumab in Participants With Locally Advanced or Metastatic Tumors
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: etigilimab
nivolumab
anti-TIGIT antibody
MPH313
Opdivo
ACTIVATE
Lead sponsor: Mereo BioPharma
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2021-02-18
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Basket study
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
timeFrame: From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days)
Secondary outcomes:
measure: Number of Participants WithTreatment-emergent Adverse Events (TEAEs), Any Adverse Events of Special Interests (AESIs), AESI Immune Related AEs, and AESI Infusion Reactions
timeFrame: 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)
measure: Disease Control Rate (DCR) as Assessed Based on RECIST v1.1
timeFrame: From first dose of study drug until the date of first BOR (CR, PR, or SD) (maximum exposure: 638 days)
measure: Duration of Response (DoR) as Assessed Based on RECIST v1.1
timeFrame: 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)
measure: Duration of Stable Disease (DoSD) as Assessed Based on RECIST v1.1
timeFrame: 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)
measure: Serum Concentrations of Etigilimab
timeFrame: Pre-infusion and 15 minutes post-infusion on Cycle 1 Day 1 and Cycle 4 Day 43
measure: Number of Participants With Anti-drug Antibodies (ADA) to Etigilimab
timeFrame: 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)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mereo Investigator Site
state: Arizona
city: Greenbrae
country: United States
facility: Mereo Investigator Site
state: California
city: Los Angeles
country: United States
facility: Mereo Investigator Site
state: California
city: Jacksonville
country: United States
facility: Mereo Investigator Site
state: Florida
city: Boston
country: United States
facility: Mereo Investigator Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Mereo Investigator Site
state: Michigan
city: Rochester
country: United States
facility: Mereo Investigator Site
state: Minnesota
city: New York
country: United States
facility: Mereo Investigator Site
state: New York
city: Durham
country: United States
facility: Mereo Investigator Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Mereo Investigator Site
state: Oklahoma
city: Nashville
country: United States
facility: Mereo Investigator Site
state: Tennessee
city: Houston
country: United States
facility: Mereo Investigator Site
state: Texas
city: West Valley City
country: United States
facility: Mereo Investigator Site
state: Utah
city: Fairfax
country: United States
facility: Mereo Investigator Site
state: Virginia
city: London
country: United Kingdom
facility: Royal Marsden
city: London
country: United Kingdom
facility: Sarah Cannon UK
Study officials:
References: