A Study of BGB-30813 Alone or in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors

A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the DGKζ Inhibitor BGB-30813, Alone or in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced or Metastatic Solid Tumors

This is a First in Human (FIH) Phase 1, multicenter, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-30813 as monotherapy or in combination with tislelizumab in participants with advanced or metastatic solid tumors. The study will be conducted in 2 parts: Phase 1a dose escalation and Phase 1b dose expansion.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: BGB-30813; Drug: Tislelizumab

Detailed Description

This study will test whether taking BGB-30813 alone or with tislelizumab can help treat patients with cancer that has spread throughout the body or is locally advanced. The two main goals of the study are to ensure that the treatments are safe by monitoring side effects and to determine the number of participants who respond well to treatment either partially or completely. The combination of BGB-30813 with other drugs that target immune checkpoints may work together to stop or prevent cancer activity.

Approximately 200 participants will participate. In the first part of the study, participants will be given different doses of BGB-30813 either alone or with tislelizumab to find the dose that is best tolerated. BGB-30813 will be given orally and tislelizumab will be given through a vein. In the second part of the study, the selected dose of BGB-30813, either alone or with tislelizumab, will be given to a larger number of participants from different parts of the world to see if the treatments can improve the signs and symptoms of their cancer. Treatments will continue until participants are no longer considered to be receiving benefits, have unacceptable side effects, or withdraw consent.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
• China
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Madrid, Spain, 28040
    • Start Madrid Fundacion Jimenez Diaz
• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-1915
      • Hackensack University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-3907
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-6028
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Phase 1a (Dose Escalation):

  • Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received available standard systemic therapy or for whom treatment is not available or not tolerated and who have not received any prior therapy targeting diacylglycerol kinase (DGK)
  • Eligible tumor types are immune sensitive solid tumors such as non-small cell lung cancer (NSCLC), head neck squamous cell cancer (HNSCC), small cell lung cancer, hepatocellular carcinoma, esophageal cancer, gastric or gastroesophageal carcinoma, nasopharyngeal carcinoma, triple-negative breast cancer, urothelial carcinoma, renal cell carcinoma, cervical cancer, endometrial carcinoma, cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, mesothelioma, microsatellite instability (MSI)-high, tumor mutation burden (TMB)-high, or mismatch repair deficient solid tumors
  • Prior checkpoint inhibitor (CPI) therapy is allowed

• Phase 1b (Dose Expansion):

  • Participants with selected advanced or metastatic solid tumors including NSCLC, HNSCC, and additional potential tumor types to be defined based on emerging data
• ≥ 1 measurable lesion per RECIST v1.1
• Eastern Cooperative Group Oncology Performance (ECOG) Performance Status score ≤ 1
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study
• Adequate organ function as indicated by the following laboratory values up to first dose of study treatment: Hemoglobin≥ 90 grams per liter (g/L), Absolute neutrophil count ≥ 1.5 x 109/L , Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (< 3 x ULN for participants with Gilbert syndrome ), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

Exclusion Criteria:

• Previous therapy targeting DGK
• Active leptomeningeal disease or uncontrolled symptomatic central nervous system (CNS) metastasis
• Active autoimmune diseases or history of autoimmune diseases that may relapse
• 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
• Systemic anticancer therapy, including chemotherapy ≤ 21 days or 5 half-lives (whichever is shorter) before the first dose of study drugs
• ≥ Grade 3 immune-mediated adverse events on prior immuno-oncology agent (anti-PD-1 or anti-CTLA4 antibodies or other experimental drugs)

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 Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Dose Escalation Part A: BGB-30813 Monotherapy	Drug: BGB-30813; Specified dose administered on specified days
Experimental: Phase 1a: Dose Escalation Part B: BGB-30813 + Tislelizumab	Drug: BGB-30813; Specified dose administered on specified days; Drug: Tislelizumab; Specified dose administered on specified days; Other Names: BGB-A317
Experimental: Phase 1b: Dose Expansion BGB-30813 in Combination with Tislelizumab	Drug: BGB-30813; Specified dose administered on specified days; Drug: Tislelizumab; Specified dose administered on specified days; Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Dose Escalation: Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Dose-Limiting Toxicities (DLTs)	Number of participants experiencing AEs and SAEs, including physical examination findings, electrocardiograms (ECGs), and lab assessments as needed; and AEs meeting protocol-defined DLT criteria.	From the first dose of study drug(s) to 30 days after the last dose; approximately 6 months
Phase 1a: Dose Escalation: The Maximum Tolerated Dose (MTD) and Maximum Administered Dose (MAD)	The MTD or MAD is defined as the highest dose at which 30% of participants experience a DLT or the highest dose administered, respectively.	Up to approximately 6 months
Phase 1a and 1b: Recommended dose(s) for Expansion (RDFE[s]) of BGB-30813 Alone or in Combination with Tislelizumab	The RDFE(s) of BGB-30813 alone or in combination with tislelizumab, determined based upon the MTD or MAD and other relevant data.	Up to approximately 6 months
Phase 1b: Dose Expansion: Overall Response Rate (ORR) as Determined by the Investigator	ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as determined from tumor assessments by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Dose Escalation: ORR as Determined by the Investigator	ORR is defined as the percentage of participants who had confirmed CR or PR as determined from tumor assessments by the investigator per RECIST version 1.1	Up to approximately 12 months
Phase 1a: Dose Escalation: Maximum Observed Plasma Concentration (Cmax) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab		Up to approximately 6 months
Phase 1a: Dose Escalation: Observed Plasma Trough Concentration (Ctrough) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab		Up to approximately 6 months
Phase 1a: Dose Escalation: Area under the concentration-time curve (AUC) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab		Up to approximately 6 months
Phase 1a: Dose Escalation: Half-life (t1/2) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab		Up to approximately 6 months
Phase 1b: Dose Expansion: Number of Participants Experiencing AEs and SAEs	Number of participants experiencing AEs and SAEs, including physical examination findings, ECGs, and lab assessments as needed.	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
Phase 1b: Dose Expansion: Duration of Response (DOR)	DOR is defined as the time from the first determination of an overall response assessed by the investigator using RECIST v1.1, until the first documentation of disease progression or death, whichever comes first.	Up to approximately 12 months
Phase 1b: Dose Expansion: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with best overall response (BOR) of complete Response (CR), Partial Response (PR), or stable disease assessed by the investigator using RECIST v1.1.	Up to approximately 12 months
Phase 1b: Dose Expansion: Progression Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drugs to the date of the first documentation of disease progression assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Up to approximately 12 months
Phase 1b: Dose Expansion: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with BOR of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by the investigator using RECIST v1.1.	Up to approximately 12 months
Phase 1b: Dose Expansion: Plasma concentrations of BGB-30813, and its metabolite, BGB-33481		Up to approximately 6 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2023
• Primary Completion (Actual): August 20, 2025
• Study Completion (Actual): August 20, 2025

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Immunotherapy; HNSCC; Advanced or Metastatic Solid Tumors; Tislelizumab; Anti-PD-1 Monoclonal Antibody; BGB-A317; DGKζ Inhibitor; BGB-30813; Diacylglycerol kinase
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents, Immunological; Antineoplastic Agents; tislelizumab
• Other Study ID Numbers: BGB-A317-30813-101; U1111-1290-6118 (Other Identifier: WHO); 2023-503996-38 (EudraCT Number); CTR20233404 (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.

BeiGene 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.: No