Phase 1 First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06422520
• Other study ID #: BGB-C354-101
• Secondary ID: 2024-513280-11-0
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 24, 2024
• Est. completion date: November 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 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, and higher frequencies may be considered based on emerging data. The maximum treatment duration will be up to 2 years. - The study duration is estimated to be approximately 5 years.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 62
• Est. completion date: November 30, 2026
• Est. primary completion date: November 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. 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• BGB-C354
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	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-limitingtoxicity (DLT) criteria	Up to approximately 2 years
Primary	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	Up to approximately 2 years
Primary	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	Up to approximately 2 years
Primary	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).	Up to approximately 2 years
Primary	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.	Up to approximately 2 years
Secondary	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.	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	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.determined from tumor assessments by the investigator using RECIST v1.1.	Up to approximately 2 years
Secondary	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	Up to approximately 2 years
Secondary	Maximum observed plasma concentration (Cmax) for BGB-C354		Up to approximately 2 years
Secondary	Minimum observed plasma concentration (Cmin) for BGB-C354		Up to approximately 2 years
Secondary	Time to maximum plasma concentration (Tmax) for BGB-C354		Up to approximately 2 years
Secondary	Half-life (t1/2) for BGB-C354		Up to approximately 2 years
Secondary	Area under the concentration-time curve (AUC) for BGB-C354		Up to approximately 2 years
Secondary	Apparent clearance (CL/F) for BGB-C354		Up to approximately 2 years
Secondary	Apparent volume of distribution (Vz/F) for BGB-C354		Up to approximately 2 years
Secondary	Accumulation ratio for BGB-C354		Up to approximately 2 years
Secondary	Number of participants with anti-drug antibodies (ADAs) to BGB-C354		Up to approximately 2 years
Secondary	Serum concentration of BGB-C354		Up to approximately 2 years