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

NCT03379259 | Terminated Phase 1 Results

• 2 other identifiers: BGB-900-1012018-000265-37
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  Up to 33.5 months

• Phase 1 A: Recommended Phase 2 Dose (RP2D) for BGB-333

  RP2D for BGB-A333 alone and in combination with tislelizumab was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 1800 mg.

  Up to 28 months

• Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1

  The ORR is defined as the percentage of participants who had confirmed Complete Response (CR) or Partial response (PR) assessed by investigator using RECIST version 1.1

  Up to 33.5 months

Secondary Outcomes (10)

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

  Up to 33.5 months

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

  Up to 33.5 months

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

  Up to 33.5 months

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

  Up to 33.5 months

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

  Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21

Study Arms (4)

Phase 1A: BGB-A333 monotherapy dose escalation

EXPERIMENTAL

Drug: BGB-A333

Phase 2A: BGB-A333 monotherapy dose expansion

EXPERIMENTAL

Drug: BGB-A333

Phase 1B: BGB-A333 and BGB-A317 dose confirmation

EXPERIMENTAL

Drug: BGB-A333; Drug: BGB-A317

Phase 2B: BGB-A333 and BGB-A317 dose expansion

EXPERIMENTAL

Drug: BGB-A333; Drug: BGB-A317

Interventions

BGB-A333 DRUG

Anti-PD-L1 antibody

Phase 1A: BGB-A333 monotherapy dose escalation; Phase 1B: BGB-A333 and BGB-A317 dose confirmation; Phase 2A: BGB-A333 monotherapy dose expansion; Phase 2B: BGB-A333 and BGB-A317 dose expansion

BGB-A317 DRUG

Anti-PD-1 antibodies

Also known as: Tislelizumab

Phase 1B: BGB-A333 and BGB-A317 dose confirmation; Phase 2B: BGB-A333 and BGB-A317 dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
• Has adequate organ function

You may not qualify if:

• Active brain or leptomeningeal metastasis.
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• 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)
• Concurrent participation in another therapeutic clinical trial.
• Received prior therapies targeting PD-1 or PD-L1.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (8)

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Institut Catala Doncologia

Barcelona, 08908, Spain

Location

Start Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Related Publications (1)

• Desai J, Fong P, Moreno V, Frentzas S, Meniawy T, Markman B, Voskoboynik M, Rahman T, Budha N, Wu J, Marlow J, Yang S, Calvo E, Martin-Liberal J. A Phase 1/2 study of the PD-L1 inhibitor, BGB-A333, alone and in combination with the PD-1 inhibitor, tislelizumab, in patients with advanced solid tumours. Br J Cancer. 2023 Apr;128(8):1418-1428. doi: 10.1038/s41416-022-02128-3. Epub 2023 Feb 16.

  PMID: 36797356 DERIVED

MeSH Terms

Interventions

tislelizumab

Limitations and Caveats

Phase 2A of the study was not initiated nor conducted since BGB-A333 as a monotherapy treatment beyond the completion of dose escalation in Phase 1A was not pursued.

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: December 20, 2017
• Study Start: November 27, 2017
• Primary Completion: September 8, 2020
• Study Completion: September 8, 2020
• Last Updated: October 26, 2024
• Results First Posted: November 9, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

NZ (1); ES (3); AU (4)