Overview

This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of the BGB-B2033 in participants with advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors, non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC). The study will also identify the recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab for subsequent studies. BGB-B2033 will be administered by intravenous infusion. The Phase 1 study will be conducted in 2 parts: Part A (Monotherapy Dose Escalation and Safety Expansion) and Part B (Combination Dose Escalation and Safety Expansion).

Eligibility

Inclusion Criteria:

1. Participants with any of the following unresectable locally advanced or metastatic tumor types:
   1. HCC
   2. AFP-producing GC (serum AFP > 20 ng/mL or tumor tissue AFP positive by a validated IHC assay according to local testing criteria)
   3. germ cell tumor including extragonadal yolk sac tumors (located in mediastinum, vagina, brain, and retroperitoneum, etc) and non-dysgerminomas
   4. GPC3-positive squamous NSCLC
2. ≥ 1 evaluable lesion for dose escalation and ≥ 1 measurable lesion for safety

   expansion, per RECIST v1.1

3. ECOG Performance Status score ≤ 1
4. Adequate organ functions
5. Tumor tissues will be required for certain parts of the study

Exclusion Criteria:

1. Prior therapy targeting glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (also known as CD137)
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
3. Active autoimmune diseases or history of autoimmune diseases that may relapse
4. Any malignancy ≤ 2 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
5. 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 drug(s).
6. Certain comorbidities in the lung, heart, bleeding condition and infections.

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