BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

The primary objective of this study is to assess the safety and tolerability of BGB-15025 alone and in combination with tislelizumab; and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 doses (RP2D) of BGB-15025 alone and in combination with tislelizumab in participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Tislelizumab; Drug: BGB-15025; Drug: Oxaliplatin; Drug: Capecitabine; Drug: nab-paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, NSW 2031
      • Prince of Wales Hospital
  • South Australia
    • Windsor Gardens, South Australia, Australia, SA 5087
      • Ashford Cancer Centre Research Northeast
  • Victoria
    • Melbourne, Victoria, Australia, VIC 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Linear Clinical Research
• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • GangnamGu, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center
    • SeochoGu, Seoul Teugbyeolsi, South Korea, 06591
      • The Catholic University of Korea, Seoul St Marys Hospital
    • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital Yonsei University Health System
    • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center
• United States
  • New York
    • New York, New York, United States, 10029-6504
      • Icahn School of Medicine at Mount Sinai
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-4427
      • Ut Health San Antonio Mays Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused, and who have not received prior therapy targeting HPK1
2. Phase 1b (dose expansion): Participant with histologically or cytologically confirmed advanced, and metastatic including non-small cell lung cancer, and gastric/Gastroesophageal junction cancer that have no prior systemic treatment for advanced disease and esophageal squamous cancer who have progressed following systemic anticancer therapies
3. At least 1 measurable lesion as defined per RECIST 1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
5. Adequate organ function as indicated by the following laboratory values up to first dose of study treatment: Hemoglobin≥ 90 g/L, Absolute neutrophil count ≥ 1.5 x 10^9/L , Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome ), AST and ALT≤ 2.5 x ULN

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled and untreated brain metastasis.
2. Active autoimmune diseases or history of autoimmune diseases that may relapse
3. Any active malignancy ≤ 2 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
4. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study treatment
5. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including but not limited to pulmonary fibrosis, acute lung diseases, etc.
6. For Cohort A: Known actionable mutations (including but not limited to epidermal growth factor receptor (EGFR) gene, anaplastic lymphoma kinase (ALK) fusion oncogene, BRAF V600E, RET, MET, and ROS1, for which a targeted therapy has been approved by the local health authority and available.
7. For Cohort B: Diagnosed with G/GEJ adenocarcinoma with positive HER2 status

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: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Dose Escalation; Part A: Participants will receive once daily of BGB-15025 monotherapy in sequential cohorts of approximately 7 increasing doses Part B: Participants will receive once daily of BGB-15025 in sequential cohorts plus 200mg tislelizumab on day 1 of each 21-day cycle (combination therapy )	Drug: Tislelizumab; Administered 200 mg intravenous (IV) infusion; Other Names: BGB-A317; Drug: BGB-15025; Administered orally once or twice daily (QD or BID)
Experimental: Phase 1b: Dose Expansion; Phase 1b dose expansion will begin based upon the recommended doses for expansion (RDFE) for BGB-15025 alone or in combination with tislelizumab, and with or without chemotherapy as determined from Phase 1a	Drug: Paclitaxel; Administered intravenously; Drug: Carboplatin; Administered intravenously; Drug: Cisplatin; Administered intravenously; Drug: Pemetrexed; Administered intravenously; Drug: Tislelizumab; Administered 200 mg intravenous (IV) infusion; Other Names: BGB-A317; Drug: BGB-15025; Administered orally once or twice daily (QD or BID); Drug: Oxaliplatin; Administered intravenously; Drug: Capecitabine; Administered intravenously; Drug: nab-paclitaxel; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Number of participants with dose limiting toxicities (DLTs)	Participants will be considered evaluable for DLTs if they 1) received ≥ 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.	Up to 3 Years
Phase 1a: Number of Participants Experiencing Adverse Events (AEs)		Up to 4 Years
Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 4 years
The maximum tolerated dose (MTD) of BGB-15025	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 Years
Recommended Doses for Expansion (RDFE) of BGB-15025 monotherapy	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 years
RDFE of BGB-15025 in combination with tislelizumab	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 years
Phase 1b: Overall Response Rate (ORR) as assessed by the investigator		Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Overall Response Rate (ORR) as assessed by the investigator		Up to 3 years
Duration Of Response (DOR) as assessed by the investigator		Up to 3 years
Disease Control Rate (DCR) as assessed by the investigator		Up to 3 years
Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Time to maximum plasma concentration (Tmax) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Half-life of (t1/2) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Area under the concentration-time curve (AUC) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Apparent clearance (CL/F) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Apparent volume of distribution (Vz/F) of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Accumulation Ratio for Cmax of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Accumulation Ratio for AUC of BGB-15025		Predose up to 8 hours postdose
Phase 1a: Metabolite to parent ratio for BGB-15025 and its metabolite		Predose up to 8 hours postdose
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)		Up to 3 years
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 3 years
Phase 1b: Plasma Concentrations of BGB-15025		Predose up to 8 hours postdose
Phase 1b: Plasma Concentrations of the metabolite		Predose up to 8 hours postdose
Phase 1b: Number of participants with dose limiting toxicities (DLTs)	Participants will be considered evaluable for DLTs if they 1) received ≥ 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.	Up to 1 year

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): October 17, 2025
• Study Completion (Actual): May 15, 2026

Study Registration Dates

• First Submitted: November 25, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Platinum Compounds; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; 130-nm albumin-bound paclitaxel; tislelizumab
• Other Study ID Numbers: BGB-A317-15025-101; CTR20212721 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes