Advanced Solid Tumor
Conditions
Keywords
BG-C9074, Tislelizumab, Advanced Solid Tumors, first-in-human, B7H4
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 other anticancer therapies in patients with advanced solid tumors.
Interventions
DRUGBG-C9074
administered by intravenous infusion
DRUGTislelizumab
administered by intravenous infusion
DRUGBevacizumab
administered by intravenous infusion
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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).
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. |
| Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074 | 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 |
| Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074. | 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 |
| Phase 1b: Overall Response Rate (ORR) as monotherapy and in combination with tislelizumab | 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. |
| Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with bevacizumab or tislelizumab | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: ORR as monotherapy and in combination with tislelizumab | 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. |
| Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab | 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. |
| Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression | 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 |
| Duration of Response (DOR) | 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 |
| Duration of Response (DOR) per B7-H4 protein expression | 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 |
| Disease Control Rate (DCR) | 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 |
| Disease Control Rate (DCR) per B7-H4 protein expression | 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 |
| Clinical Benefit Rate (CBR) | 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. |
| Clinical Benefit Rate (CBR) per B7-H4 protein expression | 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 |
| Phase 1b: Progression Free Survival (PFS) | 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. |
| Phase 1b: Number of Participants with AEs and SAEs | Approximately 3 years | Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments. |
| Maximum observed plasma concentration (Cmax) for BG-C9074 | Twice in the first four months | — |
| Minimum observed plasma concentration (Cmin) for BG-C9074 | Approximately 3 years | — |
| Time to reach maximum observed plasma concentration (Tmax) for BG-C9074 | Twice in the first four months | — |
| Half-life (t1/2) for BG-C9074 | Twice in the first four months | — |
| Area under the concentration-time curve (AUC) for BG-C9074 | Twice in the first four months | — |
| Apparent clearance (CL/F) for BG-C9074 | Twice in the first four months | — |
| Apparent volume of distribution (Vz/F) for BG-C9074 | Twice in the first four months | — |
| Accumulation ratio for BG-C9074 | Twice in the first four months | — |
| Plasma concentrations for BG-C9074 | Approximately 3 years | — |
| Phase 1a: Number of participants with anti-drug antibodies (ADAs) to BG-C9074 and tislelizumab | Approximately 3 years | — |
| Phase 1b: Number of participants with anti-drug antibodies (ADAs) to BG-C9074 | Approximately 3 years | — |
| Serum concentration of BG-C0974 | Approximately 3 years | — |
| Serum concentration of Tislelizumab | Approximately 3 years | — |
Countries
Australia, Brazil, China, Japan, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed