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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 308
- 试验地点
- 56
- 主要终点
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •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.
- •≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- •Able to provide an archived tumor tissue sample.
- •Adequate bone marrow and organ function.
- •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).
- •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).
排除标准
- •Prior treatment with a B7 homolog 4 (B7H4)-targeting antibody-drug conjugate (ADC) or an ADC with a topoisomerase 1 inhibitor (TOP1i) payload.
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •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).
- •History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen (including intermittent use) at baseline.
- •Uncontrolled diabetes.
- •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.
研究组 & 干预措施
Phase 1a: Part D (Japan Cohort)
A separate cohort in Japan will evaluate the safety of BG-C9074 monotherapy in Japanese participants with select solid tumors
干预措施: BG-C9074 (Drug)
Phase 1a: Part C (Combination Therapy Dose Escalation)
BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE).
干预措施: BG-C9074 (Drug)
Phase 1b: Monotherapy Dose Expansion
The monotherapy dose expansion phase will begin once the BG-C9074 monotherapy RDFE and dosing schedule have been determined from Parts A and B in Phase 1a.
干预措施: BG-C9074 (Drug)
Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab)
This arm will assess BG-C9074 plus tislelizumab as first-line therapy in select solid tumors after completion of the dose escalation phase.
干预措施: BG-C9074 (Drug)
Phase 1a: Part C (Combination Therapy Dose Escalation)
BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE).
干预措施: Tislelizumab (Drug)
Phase 1a: Part B (Monotherapy Safety Expansion)
BG-C9074 dose levels that have been determined to be safe and tolerable in Part A will be investigated.
干预措施: BG-C9074 (Drug)
Phase 1a: Part A (Monotherapy Dose Escalation)
BG-C9074 monotherapy dose escalation
干预措施: BG-C9074 (Drug)
Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab)
This arm will assess BG-C9074 plus tislelizumab as first-line therapy in select solid tumors after completion of the dose escalation phase.
干预措施: Tislelizumab (Drug)
Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus bevacizumab)
This arm will assess BG-C9074 plus bevacizumab in select solid tumors participants after establishing the recommended monotherapy dose and schedule.
干预措施: Bevacizumab (Drug)
Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus bevacizumab)
This arm will assess BG-C9074 plus bevacizumab in select solid tumors participants after establishing the recommended monotherapy dose and schedule.
干预措施: BG-C9074 (Drug)
结局指标
主要结局
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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
时间窗: 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.
时间窗: 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
时间窗: 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
时间窗: 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.
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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
时间窗: 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.
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)
- Phase 1a: ORR as monotherapy and in combination with tislelizumab(Approximately 3 years)
- Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab(Approximately 3 years)
- Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression(Approximately 3 years)
- Duration of Response (DOR)(Approximately 3 years)
- Duration of Response (DOR) per B7-H4 protein expression(Approximately 3 years)
- Disease Control Rate (DCR)(Approximately 3 years)
- Disease Control Rate (DCR) per B7-H4 protein expression(Approximately 3 years)
- Clinical Benefit Rate (CBR)(Approximately 3 years)
- Clinical Benefit Rate (CBR) per B7-H4 protein expression(Approximately 3 years)
- Phase 1b: Progression Free Survival (PFS)(Approximately 3 years)
- Phase 1b: Number of Participants with AEs and SAEs(Approximately 3 years)
- 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)
- 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)
- Maximum observed plasma concentration (Cmax) for BG-C9074(Twice in the first four months)
- Phase 1a: ORR as monotherapy and in combination with tislelizumab(Approximately 3 years)
- Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab(Approximately 3 years)
- Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression(Approximately 3 years)
- Duration of Response (DOR)(Approximately 3 years)
- Duration of Response (DOR) per B7-H4 protein expression(Approximately 3 years)
- Disease Control Rate (DCR)(Approximately 3 years)
- Disease Control Rate (DCR) per B7-H4 protein expression(Approximately 3 years)
- Clinical Benefit Rate (CBR)(Approximately 3 years)
- Clinical Benefit Rate (CBR) per B7-H4 protein expression(Approximately 3 years)
- Phase 1b: Progression Free Survival (PFS)(Approximately 3 years)
- Phase 1b: Number of Participants with AEs and SAEs(Approximately 3 years)