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A Phase 1/2 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors

ConditionsMetastatic Hepatocellular CarcinomaLocal Advanced Hepatocellular CarcinomaAlpha-fetoprotein (AFP)-Producing Gastric CancerExtragonadal Yolk Sac TumorsGlypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBeOne Medicines

About this trial

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of BGB-B2033 alone or in combination with tislelizumab, with or without bevacizumab, in adults 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 determine the recommended Phase 2 dose (RP2D) of BGB-B2033 when given alone or in combination with tislelizumab and bevacizumab. The main questions it aims to answer are:

* Is BGB-B2033 safe and tolerable when given alone or in combination with tislelizumab, with or without bevacizumab? * How does the body process BGB-B2033, and what are its effects on the body? * Does BGB-B2033 show preliminary antitumor activity in participants with advanced or metastatic cancer?

Researchers will evaluate different doses and treatment combinations to determine the safest and most appropriate dose of BGB-B2033 for further study.

Participants will:

* Receive BGB-B2033 by intravenous infusion, either alone or in combination with tislelizumab, with or without bevacizumab. * Have regular assessments to monitor safety, side effects, how their body processes and responds to BGB-B2033, and whether their cancer responds to treatment.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Hepatocellular carcinoma (HCC): Histologically or cytologically confirmed HCC that is either Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC Stage B that is not amenable to, or has progressed after, loco-regional therapy and is not eligible for a curative treatment approach.

Alpha-fetoprotein (AFP)-producing gastric cancer (GC): Histologically confirmed GC with AFP > 20 ng/mL in blood or tumor tissue positive for AFP by a validated immunohistochemistry (IHC) assay based on local or central testing.

Germ cell tumors: Histologically confirmed germ cell tumors including extragonadal yolk sac tumors (e.g., located in the mediastinum, vagina, brain, retroperitoneum), and non-dysgerminomas for which no further curative systemic treatment options exist.

Glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC): Histologically confirmed GPC3-positive squamous NSCLC with prior exposure to a checkpoint inhibitor (CPI).

Disqualifiers

Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137).

Active leptomeningeal disease or uncontrolled/untreated brain metastases.

Active autoimmune disease or a history of autoimmune disease with potential for relapse.

Any malignancy diagnosed ≤ 2 years before the first dose of study drug(s), except: The cancer type under investigation in this study, or Locally recurring malignancies previously treated with curative intent.

Trial design

Design model

Sequential

Treatments tested in this trial

  • BGB-B2033

    Drug

    Administered by intravenous infusion

  • Tislelizumab

    Drug

    Administered by intravenous infusion

  • Bevacizumab

    Drug

    Administered by intravenous infusion

Treatment groups

630 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Part A (Monotherapy Dose Escalation and Safety Expansion)Experimental treatment 1 intervention
Group B: Part B (Doublet Run-in)Experimental treatment 2 interventions
Group C: Part B (Triplet Dose Escalation)Experimental treatment 3 interventions
Group D: Part B (Triplet and Doublet Safety Expansion)Experimental treatment 3 interventions
Group E: Part C (Asia Monotherapy Dose Expansion in HCC)Experimental treatment 1 intervention
Group F: Part D (US Monotherapy Dose Expansion in HCC)Experimental treatment 1 intervention
Group G: Part E (Monotherapy Dose Expansion in HCC)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Part A and B: 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

Time frame
Up to approximately 2 years
2

Part A and B: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033

The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.

Time frame
Up to approximately 2 years
3

Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033

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

Time frame
Up to approximately 2 years
4

Parts C, D, and E: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC)

ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

Time frame
Up to approximately 2 years

Secondary outcomes

1

Part A and B: Overall Response Rate (ORR) as assessed by the investigator

ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

Time frame
Up to approximately 2 years
2

Part A and B: Duration of Response (DOR) as assessed by the investigator

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.

Time frame
Up to approximately 2 years
3

Part A and B: Disease Control Rate (DCR) as assessed by the investigator

DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments using RECIST v1.1.

Time frame
Up to approximately 2 years
4

Part A and B: Progression Free Survival (PFS) as assessed by the investigator

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 using RECIST v1.1 or death due to any cause, whichever occurs first.

Time frame
Up to approximately 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

BeOne Medicines

Lead sponsor

Source ClinicalTrials.gov
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