A Phase 1/2, Open-Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of an Anti-CTLA-4 Human Monoclonal Antibody (AGEN1884) in Subjects With Advanced or Refractory Cancer and in Subjects Who Have Progressed During Treatment With a PD-1/PD-L1 Inhibitor as Their Most Recent Therapy
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Agenus Inc.
- Enrollment
- 89
- Locations
- 11
- Primary Endpoint
- Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) of Zalifrelimab
Overview
Brief Summary
This is an open-label, Phase 1/2, multicenter study to evaluate the safety, pharmacokinetics, and pharmacodynamics of an anti-cytotoxic T lymphocyte-associated protein-4 (CTLA-4) human monoclonal antibody (zalifrelimab) in participants with advanced or refractory cancer and in participants who have progressed during treatment with a programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor as their most recent therapy.
The phase 1 portion of the study has been completed; it enrolled adult participants with refractory, advanced cancer in a 3+3 dose escalation cohort.
The phase 2 portion consisted of 51 participants who progressed during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent.
- •≥18 years of age.
- •Histological or cytological diagnosis of solid cancer or lymphoma that is considered incurable and without therapies with established benefit. Biopsy is not necessary for participants with known prior diagnosis, and clinical or radiographic evidence of recurrence. For Phase 2 only: Participants who experienced documented disease progression during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug). This cohort includes participants with histological diagnoses of hepatocellular carcinoma (HCC) (not including atypical histology such as cholangiocarcinoma mix or fibrolamellar hepatocellular carcinoma) who experienced documented disease progression during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug).
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or
- •Participants in Phase 2 with HCC should have a Child-Pugh score of A or B7 with no encephalopathy or ascites.
- •Life expectancy ≥12 weeks.
- •Adequate cardiac function (New York Heart Association \[NYHA\] class ≤II).
- •Adequate organ function, defined as absolute neutrophil count (ANC) ≥1,500×10\^6/liter (L), absolute lymphocyte count ≥500/cubic millimeters (mm\^3), hemoglobin ≥8.0 grams/deciliter (g/dL), and platelet count ≥100,000×10\^6/mm\^3 without blood growth factors or without transfusions within 1 week of first dose. For participants in Phase 2 with HCC: Platelet count ≥60×10\^6/mm\^3 and ANC ≥1,000×10\^6/L are acceptable provided that the principal investigator assesses these abnormalities as due to liver disease.
- •Adequate liver function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× institutional upper limit of normal (ULN), and bilirubin ≤1.5 milligrams/deciliter (mg/dL) × ULN. For participants in Phase 2 with HCC: AST and ALT ≤5 × ULN, bilirubin ≤2 mg/dL × ULN, and albumin ≥2.8 mg/dL.
- •Adequate renal function, defined as estimated creatinine clearance ≥50 milliliters/minute according to Cockcroft-Gault formula, or measured 24-hour creatinine clearance (or local institutional standard method).
Exclusion Criteria
- Not provided
Arms & Interventions
Zalifrelimab
Participants received zalifrelimab intravenously.
Intervention: Zalifrelimab (Drug)
Outcomes
Primary Outcomes
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) of Zalifrelimab
Time Frame: Up to 28 days
A DLT was defined as a Grade ≥3 adverse drug reaction (ADR), according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5, occurring in the DLT evaluation period (28 days after the initial administration of zalifrelimab). An ADR was defined as all noxious and unintended responses to a medicinal product, related to any dose.
Phase 1 and Phase 2: Number of Participants Experiencing Any Treatment-related Adverse Events
Time Frame: Up to 6 years
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. A treatment-related AE was one in which a causal relationship between the medicinal product and the AE was at least a reasonable possibility and could not be ruled out. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Phase 1: Maximum Drug Concentration (Cmax) of Zalifrelimab
Time Frame: Day 1 of Cycle 1 (21 days/cycle)
Blood samples were collected at designated timepoints to characterize Cmax of serum zalifrelimab following IV infusion in participants with metastatic or locally advanced solid tumors. Data reported as micrograms/milliliter (ug/mL).
Phase 1: Area Under the Drug Concentration-time Curve From 0 to 21 Days (AUC0-21d) of Zalifrelimab
Time Frame: Day 1 of Cycle 1 (21 days/cycle)
Blood samples were collected at designated timepoints to characterize AUC0-21d of serum zalifrelimab following IV infusion in participants with metastatic or locally advanced solid tumors. Data reported as hour times ug/mL (hour\*ug/mL).
Secondary Outcomes
- Phase 1 and Phase 2: Objective Response Rate (ORR)(Up to 6 years)
- Phase 1 and Phase 2: Disease Control Rate (DCR)(Up to 6 years)
- Phase 1 and Phase 2: Duration of Response (DOR)(Up to 6 years)
- Phase 1: Progression-free Survival (PFS)(Up to 6 years)
- Phase 2: PFS(Up to 6 years)
- Phase 1: Overall Survival (OS)(Up to 6 years)
- Phase 2: OS(Up to 6 years)