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

• ClinicalTrials.gov Identifier: NCT03379259
• Recruitment Status: Terminated
• First Posted: December 20, 2017
• Results First Posted: November 9, 2021
• Last Update Posted: November 9, 2021
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: BGB-A333; Drug: BGB-A317	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 27, 2017
• Actual Primary Completion Date: September 8, 2020
• Actual Study Completion Date: September 8, 2020

Arms and Interventions

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 Name: 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 Name: Tislelizumab

Outcome Measures

Primary Outcome Measures :

1. Phase 1 and Phase 2 : Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Up to 33.5 months ]
   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.
2. Phase 1 and Phase 2 : Number of Participants With Abnormalities During Physical Examinations - Ophthalmology Findings [ Time Frame: Up to 33.5 months ]
   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.
3. Phase 1 and Phase 2 : Number of Participants With Abnormal Electrocardiograms (ECG) [ Time Frame: Up to 33.5 months ]
   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.
4. Phase 1 and Phase 2 : Number of Participants With Abnormal Lab Assessment Results [ Time Frame: Up to 33.5 months ]
   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.
5. Phase 1 A: Recommended Phase 2 Dose (RP2D) for BGB-333 [ Time Frame: Up to 28 months ]
   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.
6. Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 [ Time Frame: Up to 33.5 months ]
   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

Secondary Outcome Measures :

1. Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 [ Time Frame: Up to 33.5 months ]
   ORR is defined as the percentage of participants who had confirmed CR or PR assessed by investigator using RECIST version 1.1.
2. Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1 [ Time Frame: Up to 33.5 months ]
   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.
3. Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1 [ Time Frame: Up to 33.5 months ]
   DCR is defined as the percentage of participants with best overall response of CR, PR and Stable Disease.
4. Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1 [ Time Frame: Up to 33.5 months ]
   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
5. Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 [ Time Frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 ]
   PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B pharmacokinetic (PK) parameters were not estimated due to limited sampling.
6. Phase 1: Time to Cmax (Tmax) of BGB-A333 [ Time Frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 ]
   PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
7. Phase 1:Trough Serum Concentration (Ctrough) of BGB-A333 [ Time Frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 ]
   PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
8. Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 [ Time Frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 ]
   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.
9. Phase 1: Area Under the Concentration-time Curve From 0 to 21 Days Post-dose (AUC 0-21day) of BGB-A333 [ Time Frame: Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21 ]
   PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
10. Phase 1A and Phase 2: Number of Participants With Detectable Treatment-Emergent Anti-BGB-A333 Antibodies [ Time Frame: Up to 33.5 months ]
    Treatment-emergent anti drug antibodies (ADA) was the sum of both treatment-induced ADA and treatment-boosted ADA, synonymous with "ADA Incidence."

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Australia, Victoria

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Nucleus Network

Melbourne, Victoria, Australia, 3004

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

Linear Clinical Research

Perth, Western Australia, Australia, 6009

New Zealand

Auckland City Hospital

Grafton, New Zealand, 1023

Spain

Institut Catala d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain, 08908

START Madrid. Fundacion Jimenez Diaz

Madrid, Spain, 28040

Centro Integral Oncologico Clara Campal

Madrid, Spain, 28050

Sponsors and Collaborators

BeiGene

Investigators

• Principal Investigator: Study Director; BeiGene

  Study Documents (Full-Text)

Documents provided by BeiGene:

Study Protocol  [PDF] June 12, 2018

Statistical Analysis Plan  [PDF] October 12, 2020

More Information

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03379259
• Other Study ID Numbers: BGB-900-101; 2018-000265-37 ( EudraCT Number )
• First Posted: December 20, 2017
• Results First Posted: November 9, 2021
• Last Update Posted: November 9, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Tislelizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents