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

Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-L1 Monoclonal Antibody BGB-A333 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

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 Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: BGB-A333; Drug: BGB-A317

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network
    • Melbourne, Victoria, Australia, 3004
      • Peter Maccallum Cancer Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Linear Clinical Research
• New Zealand
  • Grafton, New Zealand, 1023
    • Auckland City Hospital
• Spain
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28040
    • START Madrid. Fundacion Jimenez Diaz
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Català d'Oncologia - L'Hospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1A: BGB-A333 monotherapy dose escalation	Drug: BGB-A333; Anti-PD-L1 antibody
EXPERIMENTAL: Phase 2A: BGB-A333 monotherapy dose expansion	Drug: BGB-A333; Anti-PD-L1 antibody
EXPERIMENTAL: Phase 1B: BGB-A333 and BGB-A317 dose confirmation	Drug: BGB-A333; Anti-PD-L1 antibody; Drug: BGB-A317; Anti-PD-1 antibodies; Other Names: Tislelizumab
EXPERIMENTAL: Phase 2B: BGB-A333 and BGB-A317 dose expansion	Drug: BGB-A333; Anti-PD-L1 antibody; Drug: BGB-A317; Anti-PD-1 antibodies; Other Names: Tislelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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	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.	Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Phase 1: Time to Cmax (Tmax) of BGB-A333	PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.	Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333	PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.	Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333	PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. Actual observed time values for PK sampling, have an allowable time deviation (+/- 3 days) from the planned nominal time as pre-specified in the Visit Window section of the study protocol.	Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333	PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.	Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies	Treatment-emergent anti drug antibodies (ADA) was the sum of both treatment-induced ADA and treatment-boosted ADA, synonymous with "ADA Incidence."	Up to 33.5 months

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 27, 2017
• Primary Completion (ACTUAL): September 8, 2020
• Study Completion (ACTUAL): September 8, 2020

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (ACTUAL): December 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BGB-900-101; 2018-000265-37 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No