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
概览
- 阶段
- 1 期
- 干预措施
- BGB-C354
- 疾病 / 适应症
- Advanced Solid Tumor
- 发起方
- BeOne Medicines
- 入组人数
- 120
- 试验地点
- 20
- 主要终点
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- 状态
- 进行中（未招募）
- 最后更新
- 26天前
概览
简要总结
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. Maximum treatment duration will be up to two years.
- The study duration is estimated to be approximately 5 years.
详细描述
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
研究者
入排标准
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 of 0 or
- •Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent:
- •≥ 1 measurable lesion per RECIST v1.
- •Able to provide an archived tumor tissue sample.
- •Adequate 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 B7H3-targeted therapy.
- •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).
- •Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or 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 at baseline
- •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).
- •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 A (Monotherapy Dose Escalation)
BGB-C354 monotherapy doses at sequentially increasing levels.
干预措施: BGB-C354
Phase 1a: Part B (Safety Expansion)
Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.
干预措施: BGB-C354
Phase 1b: Part C (Monotherapy Expansion)
BGB-C354 will be administered at the recommended dose for expansion (RDFE).
干预措施: BGB-C354
Phase 1b: Part D (Combination Therapy Expansion)
BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.
干预措施: BGB-C354
Phase 1b: Part D (Combination Therapy Expansion)
BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.
干预措施: Tislelizumab
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 24 months
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354
时间窗: Approximately 1 month
Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-C354
时间窗: Approximately 24 months
The potential RDFE(s) of BGB-C354 will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 24 months
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 Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-C354 alone and in combination with tislelizumab
时间窗: Approximately 24 months
The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.
次要结局
- Phase 1a: ORR(Approximately 24 months)
- Duration of Response (DOR)(Approximately 24 months)
- Disease Control Rate (DCR)(Approximately 24 months)
- Phase 1b: Progression Free Survival (PFS)(Approximately 24 months)
- Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events(Approximately 24 months)
- Maximum observed plasma concentration (Cmax) for BGB-C354(Twice in the first 3 months)
- Minimum observed plasma concentration (Cmin) for BGB-C354(Approximately 12 months)
- Time to maximum plasma concentration (Tmax) for BGB-C354(Twice in the first 3 months)
- Half-life (t1/2) for BGB-C354(Twice in the first 3 months)
- Area under the concentration-time curve (AUC) for BGB-C354(Twice in the first 3 months)
- Apparent clearance (CL/F) for BGB-C354(Approximately 12 months)
- Apparent volume of distribution (Vz/F) for BGB-C354(Approximately 12 months)
- Accumulation ratio for BGB-C354(Approximately 12 months)
- Number of participants with anti-drug antibodies (ADAs) to BGB-C354(Approximately 12 months)
- Serum concentration of BGB-C354(Approximately 12 months)