Clinical trial NCT06233942: Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors
Official title: Phase 1a/1b Study of BG-C9074, an Antibody Drug Conjugate Targeting B7H4, as Monotherapy and in Combination With Tislelizumab in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: BG-C9074
Tislelizumab
Advanced Solid Tumors
first-in-human
B7H4
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-01-31
Enrollment: 227
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, dose finding and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C9074 alone and in combination with tislelizumab in participants with advanced solid tumors.


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 ≤ 1.
3. Participants with selected histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have been previously treated.
4. ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
5. Able to provide an archived tumor tissue sample.
6. Adequate bone marrow and 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 a B7 homolog 4 (B7H4)-targeting antibody-drug conjugate (ADC) or an ADC with a topoisomerase 1 inhibitor (TOP1i) payload.
2. Active leptomeningeal disease or uncontrolled, untreated brain metastasis
3. 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).
4. History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest \< 92%, or requirement for supplemental oxygen (including intermittent use) at baseline.
5. Uncontrolled diabetes.
6. 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: Approximately 3 years
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074
timeFrame: Approximately 18 months
measure: Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074.
timeFrame: Approximately 18 months
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Approximately 3 years
measure: Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with tislelizumab
timeFrame: Approximately 30 months
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: Approximately 3 years
measure: Clinical Benefit Rate (CBR)
timeFrame: Approximately 3 years
measure: Phase 1b: Progression Free Survival (PFS)
timeFrame: Approximately 3 years
measure: Phase 1b: Number of Participants with AEs and SAEs
timeFrame: Approximately 3 years
measure: Maximum observed plasma concentration (Cmax) for BG-C9074
timeFrame: Twice in the first four months
measure: Minimum observed plasma concentration (Cmin) for BG-C9074
timeFrame: Approximately 3 years
measure: Time to reach maximum observed plasma concentration (Tmax) for BG-C9074
timeFrame: Twice in the first four months
measure: Half-life (t1/2) for BG-C9074
timeFrame: Twice in the first four months
measure: Area under the concentration-time curve (AUC) for BG-C9074
timeFrame: Twice in the first four months
measure: Apparent clearance (CL/F) for BG-C9074
timeFrame: Twice in the first four months
measure: Apparent volume of distribution (Vz/F) for BG-C9074
timeFrame: Twice in the first four months
measure: Accumulation ratio for BG-C9074
timeFrame: Twice in the first four months
measure: Plasma concentrations for BG-C9074
timeFrame: Approximately 3 years
measure: Number of participants with anti-drug antibodies (ADAs) to BG-C9074
timeFrame: Approximately 3 years
measure: Serum concentration of BG-C0974
timeFrame: Approximately 3 years
measure: Serum concentration of Tislelizumab
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center (Nccc)
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Orlando
country: United States
facility: Florida Cancer Specialist Research Institute Lake Nona
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer At Johns Hopkins
state: Maryland
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute
state: Ohio
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: Wollongong
country: Australia
facility: Cancer Care Wollongong
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Langfang
country: China
facility: Cancer Hospital Chinese Academy of Medical Scienceslangfang Branch
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Weifang
country: China
facility: Weifang Peoples Hospital
state: Shandong
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital of Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Cha Bundang Medical Center, Cha University
state: Gyeonggi-do
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: IlsandongGu GoyangSi
country: Korea, Republic of
facility: National Cancer Center (Korea)
state: Gyeonggi-do
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: