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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03379259
• Other study ID #: BGB-900-101
• Secondary ID: 2018-000265-37
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 27, 2017
• Est. completion date: September 8, 2020

Study information

• Verified date: October 2021
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: September 8, 2020
• Est. primary completion date: September 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• BGB-A333
Anti-PD-L1 antibody
• BGB-A317
Anti-PD-1 antibodies

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Nucleus Network	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Perth	Western Australia
New Zealand	Auckland City Hospital	Grafton
Spain	Institut Catala d'Oncologia - L'Hospitalet	L'Hospitalet de Llobregat	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	START Madrid. Fundacion Jimenez Diaz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Australia,  New Zealand,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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