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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
89
An anti-CTLA-4 monoclonal antibody.
City of Hope National Medical Center
Duarte, California, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Rocky Mountain Cancer Center
Denver, Colorado, United States
University of Miami Miller School of Medicine
Miami, Florida, United States
Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
Ochsner Cancer Institute
New Orleans, Louisiana, United States
Atlantic Health System/Morristown Medical Center
Morristown, New Jersey, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Texas Oncology - Austin Midtown
Austin, Texas, United States
...and 1 more locations
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) of Zalifrelimab
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.
Time frame: Up to 28 days
Phase 1 and Phase 2: Number of Participants Experiencing Any Treatment-related Adverse Events
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.
Time frame: Up to 6 years
Phase 1: Maximum Drug Concentration (Cmax) of Zalifrelimab
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).
Time frame: Day 1 of Cycle 1 (21 days/cycle)
Phase 1: Area Under the Drug Concentration-time Curve From 0 to 21 Days (AUC0-21d) of Zalifrelimab
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).
Time frame: Day 1 of Cycle 1 (21 days/cycle)
Phase 1 and Phase 2: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). BOR was defined as the best response recorded from the start of treatment until disease progression/recurrence; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters. CR was defined as disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 6 years
Phase 1 and Phase 2: Disease Control Rate (DCR)
DCR was defined as the percentage of participants who had a confirmed response (CR or PR) or stable disease (SD) without progressive disease (PD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study).
Time frame: Up to 6 years
Phase 1 and Phase 2: Duration of Response (DOR)
DOR was defined as the interval from which the date measurement criteria were met for CR or PR (whichever was first recorded) until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1, or death due to any cause, if occurring sooner than progression.
Time frame: Up to 6 years
Phase 1: Progression-free Survival (PFS)
PFS was defined as the interval from the date of first dose of investigational agent until the earliest date of PD, as determined by independent endpoint review committee assessment of objective radiographic disease assessments per RECIST v1.1, or death due to any cause if occurring sooner than progression.
Time frame: Up to 6 years
Phase 2: PFS
PFS was defined as the interval from the date of first dose of investigational agent until the earliest date of PD, as determined by independent endpoint review committee assessment of objective radiographic disease assessments per RECIST v1.1, or death due to any cause if occurring sooner than progression.
Time frame: Up to 6 years
Phase 1: Overall Survival (OS)
OS was defined as the interval from the date of first dose of investigational agent until the date of death. For participants who did not die, OS was censored at last contact date.
Time frame: Up to 6 years
Phase 2: OS
OS was defined as the interval from the date of first dose of investigational agent until the date of death. For participants who did not die, OS was censored at last contact date.
Time frame: Up to 6 years
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