A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Advanced or Metastatic Solid Tumors

BeiGene

Status and phase: Enrolling; Phase 1

Conditions: Alpha-fetoprotein (AFP)-Producing Gastric Cancer; Extragonadal Yolk Sac Tumors; Metastatic Hepatocellular Carcinoma; Metastatic Solid Tumor; Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer; Advanced Hepatocellular Carcinoma

Treatments: Drug: Tislelizumab; Drug: BGB-B2033

Study type: Interventional

Funder types: Industry

Identifiers

NCT06427941

BGB-B2033-101

Details and patient eligibility

About

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).

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Part A (Monotherapy Dose Escalation and Safety Expansion)

Experimental group

Description:

Ascending dose levels of BGB-B2033 monotherapy

Treatment:

Drug: BGB-B2033

Part B (Combination Dose Escalation and Safety Expansion)

Experimental group

Description:

Cohorts of BGB-B2033 in combination with tislelizumab

Treatment:

Drug: BGB-B2033

Drug: Tislelizumab