Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors

NCT06233942
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
308
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Lead sponsor
BeOne Medicines
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Start date
2024-04-12
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Number of sites
37
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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 other anticancer therapies in patients with advanced solid tumors.
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Short title
Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors
clinicaltrials.gov
Official title
Phase 1a/1b Study of BG-C9074, an Antibody Drug Conjugate Targeting B7H4, as Monotherapy and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-05-15
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First posted
2024-01-31
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Registry last updated
2026-07-08
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Primary completion date
2027-09-28
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Start date
2024-04-12
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Participants
308
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Participant count basis
Estimated
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Planned participants
308
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Protocol amendments
3
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Number of sites
37
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
BeOne Medicines
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06233942
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ClinicalTrials.gov ID
NCT06233942
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: Approximately 3 years

    Number of participants with AEs and SAEs (as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version \[v\] 5.0),, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.

  2. Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074

    Timeframe: Approximately 18 months

    Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 28% or the highest dose administered, respectively

  3. Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074.

    Timeframe: Approximately 18 months

    The potential RDFE(s) of BG-C9074 alone and in combination with tislelizumab will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, PK, pharmacodynamics, preliminary antitumor activity, and any other relevant data, as available

  4. Phase 1b: Overall Response Rate (ORR) as monotherapy and in combination with tislelizumab

    Timeframe: Approximately 3 years

    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.

  5. Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with bevacizumab or tislelizumab

    Timeframe: Approximately 30 months

    The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

  1. Phase 1a: ORR as monotherapy and in combination with tislelizumab

    Timeframe: Approximately 3 years

    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.

  2. Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab

    Timeframe: Approximately 3 years

    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.

  3. Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression

    Timeframe: Approximately 3 years

    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 and evaluated according to the amount of B7-H4 (B7 homolog 4) protein expressed in their tumors

  4. Duration of Response (DOR)

    Timeframe: Approximately 3 years

    Duration of response (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

  5. Duration of Response (DOR) per B7-H4 protein expression

    Timeframe: Approximately 3 years

    Duration of response (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, and evaluated according to the amount of B7-H4 protein expressed in the tumors

  6. Disease Control Rate (DCR)

    Timeframe: Approximately 3 years

    DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease, as assessed by the investigator

  7. Disease Control Rate (DCR) per B7-H4 protein expression

    Timeframe: Approximately 3 years

    DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease, as assessed by the investigator, and evaluated according to the amount of B7-H4 protein expressed in the tumors

  8. Clinical Benefit Rate (CBR)

    Timeframe: Approximately 3 years

    CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by investigator.

  9. Clinical Benefit Rate (CBR) per B7-H4 protein expression

    Timeframe: Approximately 3 years

    CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by investigato, and evaluated according to the amount of B7-H4 protein expressed in the tumors

  10. Phase 1b: Progression Free Survival (PFS)

    Timeframe: Approximately 3 years

    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.

  11. Phase 1b: Number of Participants with AEs and SAEs

    Timeframe: Approximately 3 years

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.

  12. Maximum observed plasma concentration (Cmax) for BG-C9074

    Timeframe: Twice in the first four months

  13. Minimum observed plasma concentration (Cmin) for BG-C9074

    Timeframe: Approximately 3 years

  14. Time to reach maximum observed plasma concentration (Tmax) for BG-C9074

    Timeframe: Twice in the first four months

  15. Half-life (t1/2) for BG-C9074

    Timeframe: Twice in the first four months

  16. Area under the concentration-time curve (AUC) for BG-C9074

    Timeframe: Twice in the first four months

  17. Apparent clearance (CL/F) for BG-C9074

    Timeframe: Twice in the first four months

  18. Apparent volume of distribution (Vz/F) for BG-C9074

    Timeframe: Twice in the first four months

  19. Accumulation ratio for BG-C9074

    Timeframe: Twice in the first four months

  20. Plasma concentrations for BG-C9074

    Timeframe: Approximately 3 years

  21. Phase 1a: Number of participants with anti-drug antibodies (ADAs) to BG-C9074 and tislelizumab

    Timeframe: Approximately 3 years

  22. Phase 1b: Number of participants with anti-drug antibodies (ADAs) to BG-C9074

    Timeframe: Approximately 3 years

  23. Serum concentration of BG-C0974

    Timeframe: Approximately 3 years

  24. Serum concentration of Tislelizumab

    Timeframe: Approximately 3 years

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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 previously received standard systemic therapy and whose cancer is not amenable to therapy with curative intent, and for whom further treatment is not available or not tolerated. Enrollment will be limited to participants with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, cholangiocarcinoma (CCA), endometrial cancer, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or ovarian cancer. Enrollment in the Japan cohort will be limited to participants with HR+/HER2- breast cancer, TNBC, endometrial cancer, or ovarian cancer.
  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).

  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.

Sources for eligibility
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  • Usc Norris Comprehensive Cancer Center (Nccc)Los Angeles, United StatesRecruiting
  • University of Colorado Cancer CenterAurora, United StatesRecruiting
  • Florida Cancer Specialist Research Institute Lake NonaOrlando, United StatesRecruiting
  • Sidney Kimmel Comprehensive Cancer At Johns HopkinsBaltimore, United StatesRecruiting
  • James Cancer Hospital and Solove Research InstituteColumbus, United StatesRecruiting
  • Blacktown Cancer and Haematology CentreBlacktown, AustraliaRecruiting
  • Macquarie UniversityNorth Ryde, AustraliaRecruiting
  • Cancer Care WollongongWollongong, AustraliaRecruiting
  • Princess Alexandra HospitalWoolloongabba, AustraliaRecruiting
  • Monash HealthClayton, AustraliaRecruiting
  • Cabrini Hospital MalvernMalvern, AustraliaRecruiting
  • Peter Maccallum Cancer CentreMelbourne, AustraliaRecruiting
  • Linear Clinical ResearchNedlands, AustraliaRecruiting
  • Hospital Sirio Libanes BrasiliaBrasília, BrazilRecruiting
  • Liga Norte Riograndene Contra O CancerNatal, BrazilRecruiting
  • Hospital Sao Lucas Da PucrsPorto Alegre, BrazilRecruiting
  • Instituto Nacional de Cancer Hospital Do Cancer IiRio de Janerio, BrazilRecruiting
  • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio PretoSão José do Rio Preto, BrazilRecruiting
  • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de OliveiraSão Paulo, BrazilRecruiting
  • Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E MamariaSão Paulo, BrazilRecruiting
  • Cancer Hospital Chinese Academy of Medical SciencesBeijing, ChinaRecruiting
  • Fujian Cancer HospitalFuzhou, ChinaRecruiting
  • Sun Yat Sen University Cancer CenterGuangzhou, ChinaRecruiting
  • Harbin Medical University Cancer HospitalHarbin, ChinaRecruiting
  • Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaRecruiting

And 12 more, listed on the interactive page.

Sources for sites
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Other registry identifiers

  • jRCT2031250755
Sources for references
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Related records

Drugs (2)

Lead sponsors (1)

Targets (2)