A First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

NCT06422520 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: BGB-C354-1012024-513280-11-00
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 14

Brief Summary

This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354 alone and in combination with tislelizumab in participants with advanced solid tumors. Study details include:

• The study will be conducted in 2 phases: Phase 1a (Monotherapy Dose Escalation and Safety Expansion) and Phase 1b (Dose Expansion).
• The visit frequency will be approximately every 21 days during study treatment. Maximum treatment duration will be up to two years.
• The study duration is estimated to be approximately 5 years.

Conditions

Advanced Solid Tumor

Keywords

BGB-C354; Tislelizumab; First-in-human; Advanced solid tumor; Anti-PD-1 Monoclonal Antibody; B7H3; antibody drug conjugate

Outcome Measures

Primary Outcomes (5)

• Phase 1a: 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 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria

  Approximately 24 months

• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354

  Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively

  Approximately 1 month

• Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-C354

  The potential RDFE(s) of BGB-C354 will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available

  Approximately 24 months

• Phase 1b: 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).

  Approximately 24 months

• Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-C354 alone and in combination with tislelizumab

  The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

  Approximately 24 months

Secondary Outcomes (15)

• Phase 1a: ORR

  Approximately 24 months

• Duration of Response (DOR)

  Approximately 24 months

• Disease Control Rate (DCR)

  Approximately 24 months

• Phase 1b: Progression Free Survival (PFS)

  Approximately 24 months

• Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events

  Approximately 24 months

Study Arms (4)

Phase 1a: Part A (Monotherapy Dose Escalation)

EXPERIMENTAL

BGB-C354 monotherapy doses at sequentially increasing levels.

Drug: BGB-C354

Phase 1a: Part B (Safety Expansion)

EXPERIMENTAL

Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.

Drug: BGB-C354

Phase 1b: Part C (Monotherapy Expansion)

EXPERIMENTAL

BGB-C354 will be administered at the recommended dose for expansion (RDFE).

Drug: BGB-C354

Phase 1b: Part D (Combination Therapy Expansion)

EXPERIMENTAL

BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.

Drug: BGB-C354; Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Administered by intravenous infusion

Phase 1b: Part D (Combination Therapy Expansion)

BGB-C354 DRUG

Administered by intravenous infusion

Phase 1a: Part A (Monotherapy Dose Escalation); Phase 1a: Part B (Safety Expansion); Phase 1b: Part C (Monotherapy Expansion); Phase 1b: Part D (Combination Therapy Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent:
• ≥ 1 measurable lesion per RECIST v1.1.
• Able to provide an archived tumor tissue sample.
• Adequate organ function.
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 7 months after the last dose of study drug(s).
• Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).

You may not qualify if:

• Prior treatment with B7H3-targeted therapy.
• For Part B and Phase 1b: Prior treatment with antibody drug conjugates (ADCs) with topoisomerase I inhibitor payload (for Phase 1b, unless otherwise specified for specific cohorts).
• Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or untreated brain metastasis
• Any malignancy ≤ 2 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
• History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest \< 92%, or requirement for supplemental oxygen at baseline
• Uncontrolled diabetes, or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium levels despite standard medical management ≤ 14 days before the first dose of study drug(s).
• Infection (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment(s).

Sponsors & Collaborators

• BeiGene: lead

Study Sites (14)

Florida Cancer Specialist Research Institute Lake Nona

Orlando, Florida, 32827-7400, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5418, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1010, United States

Location

The University of Texas Md Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Next Oncology

San Antonio, Texas, 78229-6028, United States

Location

Westmead Hospital

Westmead, New South Wales, NSW 2145, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, VIC 3065, Australia

Location

The Alfred Hospital

Melbourne, Victoria, VIC 3004, Australia

Location

One Clinical Research

Nedlands, Western Australia, WA 6009, Australia

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

Location

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110042, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Interventions

tislelizumab

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 21, 2024
• Study Start: July 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

CN (5); US (5); AU (4)