A Study of Etigilimab and Nivolumab in Participants With Locally Advanced or Metastatic Tumors
- Conditions
- Solid Tumor, AdultMetastatic Solid TumorAdvanced Solid Tumor
- Interventions
- Registration Number
- NCT04761198
- Lead Sponsor
- Mereo BioPharma
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive Etigilimab 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. Cohort B: Head and Neck Squamous Cell Carcinoma Nivolumab 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. Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naive Nivolumab 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. Cohort D (Recurrent Advanced and/or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma) Etigilimab 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. Cohort E: TMB-H + MSS Solid Tumors Etigilimab 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. Cohort E: TMB-H + MSS Solid Tumors Nivolumab 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. Cohort B: Head and Neck Squamous Cell Carcinoma Etigilimab 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. Cohort C: Cervical Carcinoma Etigilimab 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. Cohort C: Cervical Carcinoma Nivolumab 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. Cohort D (Recurrent Advanced and/or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma) Nivolumab 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. Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell) Etigilimab 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. Cohort F: Rare Tumors (Sarcoma, Uveal Melanoma, Germ Cell) Nivolumab 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. Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) Etigilimab 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. Cohort G: Endometrial Cancer Post- CPI (PD-1/PD-L1 Treated) Nivolumab 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. Cohort H: Ovarian Cancer Etigilimab 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. Cohort H: Ovarian Cancer Nivolumab 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) 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 Outcome Measures
Name Time Method 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) 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'.
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) 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.
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) 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.
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) 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.
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)
Trial Locations
- Locations (3)
Mereo Investigator Site
🇺🇸Fairfax, Virginia, United States
Royal Marsden
🇬🇧London, United Kingdom
Sarah Cannon UK
🇬🇧London, United Kingdom