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.

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.

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.