Study of BGB-A333 Alone and in Combination With Tislelizumab in Advanced Solid Tumors

Phase 2TerminatedNCT03379259

BeiGene39 enrolled

Overview

BGB-A333 is a humanized IgG1-variant monoclonal antibody against programmed cell death 1-ligand 1 (PD-L1), the ligand of an immune check point- receptor, programmed cell death-1 (PD-1). BGB-A317 is a humanized, IgG4-variant monoclonal antibody against PD-1. This study tested the safety and anti-tumor effect of BGB-A333 alone and in combination with BGB-A317 in participants with advanced solid tumors.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

BGB-A333DRUG

Anti-PD-L1 antibody

BGB-A317DRUG

Anti-PD-1 antibodies

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Histologically or cytologically confirmed advanced or metastatic disease (unresectable) that is resistant to standard therapy or for which treatment is not available, not tolerated or refused 2. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 3. Has adequate organ function Key Exclusion Criteria: 1. Active brain or leptomeningeal metastasis. 2. Active autoimmune diseases or history of autoimmune diseases that may relapse. 3. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for participants with hepatocellular carcinoma) 4. Concurrent participation in another therapeutic clinical trial. 5. Received prior therapies targeting PD-1 or PD-L1. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (8)

Monash Health

Clayton, Victoria, Australia

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Nucleus Network

Melbourne, Victoria, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

Outcomes

Primary Outcomes

Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events

Adverse events were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI-CTCAE Version 4.03 Serious Adverse Events (SAEs) were monitored from the date of informed consent. All adverse events (AEs) and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.

Time frame: Up to 33.5 months

Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings

Complete physical examination including an evaluation of 1) head, eyes, ears, nose, throat, 2) cardiovascular, 3) dermatological, 4) musculoskeletal, 5) respiratory, 6) gastrointestinal, and 7) neurological systems was required to be performed at Screening. At subsequent visits (or as clinically indicated), limited, symptom-directed physical examinations were performed. Clinically significant Ophthalmology abnormalities were collected from case report forms. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.

Time frame: Up to 33.5 months

Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG)

Central ECG data was used and the abnormality was determined by the evaluator (Investigating physician). Multiple tests such as QT, HR, PR, RR were used by the evaluator to determine abnormality. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.

Time frame: Up to 33.5 months

Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results

Lab abnormality was based on ANRIND: if the measurement value \> upper limit of normal (ULN), it was considered Abnormal. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.

Data from ClinicalTrials.gov

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Secondary Outcomes

Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1

ORR is defined as the percentage of participants who had confirmed CR or PR assessed by investigator using RECIST version 1.1.

Time frame: Up to 33.5 months

Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1

DOR was defined as the time from the first determination of an objective response per RECIST version 1.1, until the first documentation of progression or death, whichever occurs first. DOR was not evaluable in Phase 1A and Phase 1B.

Time frame: Up to 33.5 months

Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1

DCR is defined as the percentage of participants with best overall response of CR, PR and Stable Disease.

Time frame: Up to 33.5 months

Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1

PFS was defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of disease progression assessed by investigator using RECIST v1.1 or death, whichever occurs first

Time frame: Up to 33.5 months

Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333

PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B pharmacokinetic (PK) parameters were not estimated due to limited sampling.