Clinical trial NCT06422520: A First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: BGB-C354
Tislelizumab
First-in-human
Advanced solid tumor
Anti-PD-1 Monoclonal Antibody
B7H3
antibody drug conjugate
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-05-21
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.
* The study duration is estimated to be approximately 5 years.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354
timeFrame: Up to approximately 2 years
measure: Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-C354
timeFrame: Up to approximately 2 years
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-C354 alone and in combination with tislelizumab
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events
timeFrame: Up to approximately 2 years
measure: Maximum observed plasma concentration (Cmax) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Minimum observed plasma concentration (Cmin) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Time to maximum plasma concentration (Tmax) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Half-life (t1/2) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Area under the concentration-time curve (AUC) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Apparent clearance (CL/F) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Apparent volume of distribution (Vz/F) for BGB-C354
timeFrame: Up to approximately 2 years
measure: Accumulation ratio for BGB-C354
timeFrame: Up to approximately 2 years
measure: Number of participants with anti-drug antibodies (ADAs) to BGB-C354
timeFrame: Up to approximately 2 years
measure: Serum concentration of BGB-C354
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Florida Cancer Specialist Research Institute Lake Nona
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: