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

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Selected Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06427941
• Other study ID #: BGB-B2033-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 23, 2024
• Est. completion date: October 30, 2026

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: Study Director
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 proof-of-concept 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: October 30, 2026
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.

2. Age = 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older).

3. Participants with any of the following unresectable locally advanced or metastatic tumor types:

1. HCC

2. Histologically confirmed AFP-producing GC (serum AFP > 20 ng/mL or tumor tissue AFP positive by a validated IHC assay according to local testing criteria)

3. Histologically confirmed germ cell tumor including extragonadal yolk sac tumors located in mediastinum, vagina, brain, and retroperitoneum, etc) and non-dysgerminomas

4. Histologically confirmed GPC3-positive squamous NSCLC

4. = 1 evaluable lesion for dose escalation and = 1 measurable lesion for safety expansion, per RECIST v1.1

5. ECOG Performance Status score = 1

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).

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

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Hepatocellular Carcinoma
• Metastatic Solid Tumor
• Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• BGB-B2033
Administered by intravenous infusion
• Tislelizumab
Administered by intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE v 5.0/American Society for Transplantation and Cellular Therapy [ASTCT] for cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria;	Up to approximately 2 years
Primary	Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033	The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to a target toxicity rate of 30% or the highest dose administered, respectively.	Up to approximately 2 years
Primary	Recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab	The RP2D(s) will be determined based on a biologically effective dose by taking the totality of available preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration	Up to approximately 2 years
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).	Up to approximately 2 years
Secondary	Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.	Up to approximately 2 years
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments by the investigator using RECIST v1.1.	Up to approximately 2 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Up to approximately 2 years
Secondary	Serum concentration of BGB-B2033		Up to approximately 2 years
Secondary	Number of participants with anti-drug antibodies (ADAs) to BGB-B2033		Up to approximately 2 years