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BGB-A3055 Alone and in Combination With Tislelizumab in Participants With Solid Tumors

Phase 1
Active, not recruiting
Conditions
Advanced Solid Tumor
Metastatic Solid Tumor
Solid Tumor
Interventions
Registration Number
NCT05935098
Lead Sponsor
BeiGene
Brief Summary

This study aims to evaluate how safe and well-tolerated the treatment is, how the body processes it, how it works on the tumors, and whether it shows early signs of fighting cancer in people with certain advanced or metastatic solid tumors.

Key details of the study include:

* The study is expected to last about 36 months.

* Participants will receive treatment until they either no longer benefit from the treatment, experience side effects that are too severe, or choose to stop participating.

Detailed Description

The primary objective of the study is to assess the safety and tolerability of BGB-A3055 alone or in combination with Tislelizumab during dose escalation and to determine the recommended dose for expansion. During dose expansion, the primary objective will be to assess preliminary anti-tumor activity and further characterize the safety of the recommended dose for expansion.

. Around 318 participants will be enrolled in this study, and they will be assigned to different treatment groups. Both the participants and their doctors will be aware of which treatment group they are assigned to throughout the study.

The treatments, BGB-A3055 alone or in combination with Tislelizumab, will be administered intravenously to evaluate their safety and determine the highest dose that can be tolerated by participants. The study will be conducted at multiple medical centers worldwide. The expected duration of participation in this study is two years. Treatment will continue until participants no longer receive any benefits from the drugs, experience excessive side effects, or decide to withdraw their consent.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
263
Inclusion Criteria
  1. Age≥18 years on the day of signing the informed consent form (ICF) (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older).
  2. All participants are also required to demonstrate an ECOG Performance Status score of ≤1 within 3 days before the first dose of study drug(s) and have adequate organ function.
  3. Participants with histologically confirmed advanced or metastatic solid tumors associated with high CCR8 and who have previously received adequate available standard systemic therapy or for whom treatment is not available or not tolerated and who have not received any prior therapy targeting CCR8.
  4. >=1 Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  5. Participants should be able to provide archival tumor tissue samples (as block or unstained slides) or fresh biopsy if there is no archival tissue at baseline. For selected cohorts, participants should be willing to provide post-treatment fresh biopsy at specified timepoints.
  6. Females of childbearing potential and nonsterile males must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 120 days after the last dose of BGB-A3055 or tislelizumab (whichever is later), or up to 9 months after the last dose of chemotherapy, whichever is later. Females of childbearing potential must also have a negative urine or serum pregnancy test result ≤ 7 days before the first dose of study drug(s).
Exclusion Criteria
  1. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.

  2. Active autoimmune diseases or history of autoimmune diseases that may relapse

  3. Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).

  4. Participants with hepatitis B infection with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL). Participants with active hepatitis C, and participants with HIV infection.

    Note: Participants with chronic hepatitis B infection or resolved hepatitis B infection (HBV DNA < 500 IU/mL or < 2500 copies/mL) and considered stable are eligible. Participants with a negative HCV antibody test result at screening or a positive HCV antibody test result followed by a negative HCV RNA test result at screening are eligible to participate. Participants with treated HIV infection may be included if certain criteria are met.

  5. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.

  6. Grade 3 immune-mediated adverse events on prior immune-oncology agent.

  7. Cardiovascular risk factors, including but not limited to pulmonary embolism ≤ 28 days or history of acute myocardial infarction or heart failure ≤ 6 months before the first dose of study drug(s).

  8. Uncontrolled diabetes.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Phase 1a Part A: Dose Escalation (BGB-A3055 Monotherapy)BGB-A3055Different groups of participants will receive increasing doses of BGB-A3055 alone to determine the most appropriate dosage levels.
Phase 1a Part B: Dose Escalation (BGB-A3055 + tislelizumab)BGB-A3055Different groups of participants will receive increasing doses of BGB-A3055 in combination with tislelizumab to determine the most appropriate dosage levels.
Phase 1a Part B: Dose Escalation (BGB-A3055 + tislelizumab)TislelizumabDifferent groups of participants will receive increasing doses of BGB-A3055 in combination with tislelizumab to determine the most appropriate dosage levels.
Phase 1b (Dose Expansion):BGB-A3055Participants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
Phase 1b (Dose Expansion):TislelizumabParticipants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
Phase 1b (Dose Expansion):ChemotherapyParticipants will receive the recommended dose for expansion (RDFE) of BGB-A3055 in combination with tislelizumab with or without chemotherapy to provide additional information on the safety, tolerability, and potential benefits of the recommended dose.
Primary Outcome Measures
NameTimeMethod
Phase 1a: Number of participants with adverse events (AEs)Up to 2 Years

Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and the American Society for Transplantation and Cellular Therapy \[ASTCT\] consensus grading system for cytokine release syndrome \[CRS\]), and including findings from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.

Phase 1a: Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BGB-A3055Up to 2 Years

MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate of 30%. MAD is defined as the highest dose administered.

Phase 1a: Recommended dose for expansion (RDFE) of BGB-A3055 alone or in combination with tislelizumabUp to 2 Years

The RDFEs of BGB-A3055, alone or in combination with tislelizumab will be determined based on biological effectiveness taking preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration.

Phase 1b (Dose Expansion): Objective Response Rate (ORR)Up to 2 Years

ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary Outcome Measures
NameTimeMethod
Serum concentration of BGB-A3055 at specified time pointsUp to 2 Years
Phase 1b: Progression-Free Survival (PFS)Up to 2 Years

Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as determined from tumor assessments by investigators per RECIST v1.1.

Phase 1b: Number of participants with adverse events (AEs)Up to 2 Years

Number of participants with TEAEs and SAEs graded according to the NCI-CTCAE version 5.0 and the ASTCT consensus grading system for CRS, and including findings from laboratory assessments, ECGs, and physical examinations.

Phase 1b: Association of CCR8 expression with clinical efficacyUp to 2 Years

Evaluated from participant-derived tumor tissue(s) obtained before and/or after treatment with BGB-A3055 in combination with tislelizumab with or without chemotherapy, and their association with clinical efficacy.

Phase 1b: Association of PD-L1 expression with clinical efficacyUp to 2 Years

Evaluated from participant-derived tumor tissue(s) obtained before and/or after treatment with BGB-A3055 in combination with tislelizumab with or without chemotherapy, and their association with clinical efficacy.

Phase 1a: ORRUp to 2 Years

ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Time to Response (TTR)Up to 2 Years

Defined as the time from the date of the first administration of study drug(s) to the first determination of an objective response.as determined from tumor assessments by the investigators per RECIST v1.1.

Duration of Response (DOR)Up to 2 Years

Defined as the time from the first determination of an objective response to the time of first documentation of radiographic progression, as determined from tumor assessments by the investigators per RECIST v1.1, or death from any cause, whichever comes first.

Disease Control Rate (DCR)Up to 2 Years

Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease as determined from tumor assessments by the investigators per RECIST v1.1.

Clinical Benefit Rate (CBR)Up to 2 Years

Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or durable stable disease (stable disease for at least 24 weeks) as determined from tumor assessments by the investigators per RECIST v1.1.

Number of participants with anti-drug antibodies (ADAs) against BGB-A3055Up to 2 Years

Trial Locations

Locations (26)

Advent Health Cancer Institute

🇺🇸

Orlando, Florida, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

John Theurer Cancer Center Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

The University of Texas Md Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Next Dallas

🇺🇸

Irving, Texas, United States

Fred Hutchinson Cancer Research Center

🇺🇸

Seattle, Washington, United States

Chris Obrien Lifehouse

🇦🇺

Camperdown, New South Wales, Australia

Icon Cancer Centre South Brisbane

🇦🇺

South Brisbane, Queensland, Australia

Linear Clinical Research

🇦🇺

Nedlands, Western Australia, Australia

Chongqing University Cancer Hospital

🇨🇳

Chongqing, Chongqing, China

Fujian Cancer Hospital

🇨🇳

Fuzhou, Fujian, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Jiangsu Province Hospital

🇨🇳

Nanjing, Jiangsu, China

Liaoning Cancer Hospital and Institute

🇨🇳

Shenyang, Liaoning, China

Changzhi Peoples Hospital

🇨🇳

Changzhi, Shanxi, China

Tianjin Medical University Cancer Institute and Hospital

🇨🇳

Tianjin, Tianjin, China

The First Affiliated Hospital, Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, China

Centre de Lutte Contre Le Cancer Institut Bergonie

🇫🇷

Bordeaux, France

Institut Curie

🇫🇷

Paris, France

Ico Site Rene Gauducheau

🇫🇷

SaintHerblain, France

Seoul National University Bundang Hospital

🇰🇷

BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of

Samsung Medical Center

🇰🇷

GangnamGu, Seoul Teugbyeolsi, Korea, Republic of

Severance Hospital Yonsei University Health System

🇰🇷

SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center

🇰🇷

SongpaGu, Seoul Teugbyeolsi, Korea, Republic of

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