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

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BGB-C354, an Antibody-Drug Conjugate Targeting B7H3, Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Tislelizumab; Drug: BGB-C354

Detailed Description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, NSW 2145
      • Westmead Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, VIC 3065
      • St Vincents Hospital Melbourne
    • Melbourne, Victoria, Australia, VIC 3004
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • One Clinical Research
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
• United States
  • Florida
    • Orlando, Florida, United States, 32827-7400
      • Florida Cancer Specialist Research Institute Lake Nona
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5418
      • Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-6028
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent:
4. ≥ 1 measurable lesion per RECIST v1.1.
5. Able to provide an archived tumor tissue sample.
6. Adequate organ function.
7. 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).
8. 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).

Exclusion Criteria:

1. Prior treatment with B7H3-targeted therapy.
2. 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).
3. Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or untreated brain metastasis
4. 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).
5. History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen at baseline
6. 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).
7. Infection (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment(s).

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Part A (Monotherapy Dose Escalation); BGB-C354 monotherapy doses at sequentially increasing levels.	Drug: BGB-C354; Administered by intravenous infusion
Experimental: Phase 1a: Part B (Safety Expansion); Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.	Drug: BGB-C354; Administered by intravenous infusion
Experimental: Phase 1b: Part C (Monotherapy Expansion); BGB-C354 will be administered at the recommended dose for expansion (RDFE).	Drug: BGB-C354; Administered by intravenous infusion
Experimental: Phase 1b: Part D (Combination Therapy Expansion); BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.	Drug: Tislelizumab; Administered by intravenous infusion; Drug: BGB-C354; Administered by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: 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 RECIST v1.1.	Approximately 24 months
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.	Approximately 24 months
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.	Approximately 24 months
Phase 1b: 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 as determined from tumor assessments by the investigator using RECIST v1.1.	Approximately 24 months
Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events	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-limitingtoxicity (DLT) criteria	Approximately 24 months
Maximum observed plasma concentration (Cmax) for BGB-C354		Twice in the first 3 months
Minimum observed plasma concentration (Cmin) for BGB-C354		Approximately 12 months
Time to maximum plasma concentration (Tmax) for BGB-C354		Twice in the first 3 months
Half-life (t1/2) for BGB-C354		Twice in the first 3 months
Area under the concentration-time curve (AUC) for BGB-C354		Twice in the first 3 months
Apparent clearance (CL/F) for BGB-C354		Approximately 12 months
Apparent volume of distribution (Vz/F) for BGB-C354		Approximately 12 months
Accumulation ratio for BGB-C354		Approximately 12 months
Number of participants with anti-drug antibodies (ADAs) to BGB-C354		Approximately 12 months
Serum concentration of BGB-C354		Approximately 12 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2024
• Primary Completion (Actual): May 15, 2026
• Study Completion (Actual): May 15, 2026

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Tislelizumab; First-in-human; Advanced solid tumor; antibody drug conjugate; Anti-PD-1 Monoclonal Antibody; B7H3; BGB-C354
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; tislelizumab
• Other Study ID Numbers: BGB-C354-101; 2024-513280-11-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No