A First-in-Human, Phase 1/2 Trial to Assess the Safety, Tolerability and Preliminary Efficacy of Sofetabart Mipitecan (LY4170156), an Antibody-Drug Conjugate Targeting Folate Receptor α-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 575
- 试验地点
- 47
- 主要终点
- Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY4170156
研究概览
简要总结
The purpose of this study is to find out whether the study drug, Sofetabart Mipitecan (LY4170156), is safe, tolerable and effective in participants with advanced solid tumors. The study is conducted in three parts - phase Ia (dose-escalation, dose-optimization), phase Ib (dose-expansion), and phase 2 (dose expansion). The study will last up to approximately 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Have one of the following solid tumor cancers:
- •Dose Escalation: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) cancer, endometrial cancer, cervical cancer, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic cancer, or colorectal cancer (CRC)
- •Dose Optimization: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) and endometrial cancer
- •Dose Expansion: Low grade serous ovarian cancer, cervical cancer, NSCLC, TNBC, and high grade endometrioid cancer
排除标准
- •Individual with known or suspected uncontrolled central nervous system (CNS) metastases
- •Individual with history of carcinomatous meningitis
- •Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- •Individual with evidence of corneal keratopathy or history of corneal transplant
- •Any serious unresolved toxicities from prior therapy
- •Significant cardiovascular disease
- •Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms)
- •History of pneumonitis/interstitial lung disease
- •Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
研究组 & 干预措施
Sofe-M (Dose-escalation, Cohort A1)
Escalating doses of Sofe-M administered intravenously (IV)
干预措施: Sofe-M (Drug)
Sofe-M (Cohort A1 Parts A and C)
Sofe-M administered IV
干预措施: Sofe-M (Drug)
Sofe-M Alone or with Itraconazole. Drug-Drug Interaction (DDI) (Cohort A1: Arm B)
Sofe-M administered IV and itraconazole administered orally
干预措施: Sofe-M (Drug)
Sofe-M (Dose-optimization, Cohort A2)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV
干预措施: Sofe-M (Drug)
Sofe-M (Enrichment Cohort A3)
Monotherapy administered IV
干预措施: Sofe-M (Drug)
Sofe-M (Combination Cohort A4)
Combination with bevacizumab administered IV
干预措施: Sofe-M (Drug)
Sofe-M (Combination Cohort A5)
Combination with carboplatin administered IV
干预措施: Sofe-M (Drug)
Sofe-M Combination with Pembrolizumab (Dose-optimization Cohort A6)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV with pembrolizumab
干预措施: Sofe-M (Drug)
Sofe-M (Combination Cohort A5)
Combination with carboplatin administered IV
干预措施: carboplatin (Drug)
Sofe-M Combination with carboplatin and optional bevacizumab (Dose-optimization Cohort A7)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV with or without bevacizumab
干预措施: Sofe-M (Drug)
Sofe-M (Dose-expansion, Cohort B2-B4)
Sofe-M administered IV
干预措施: Sofe-M (Drug)
Sofe-M (Dose-expansion, Cohort B1)
Sofe-M administered IV
干预措施: Sofe-M (Drug)
Sofe-M Combination with carboplatin and optional bevacizumab (Dose-optimization Cohort A7)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV with or without bevacizumab
干预措施: bevacizumab (Drug)
Sofe-M Combination with carboplatin and optional bevacizumab (Dose-optimization Cohort A7)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV with or without bevacizumab
干预措施: carboplatin (Drug)
Sofe-M Alone or with Itraconazole. Drug-Drug Interaction (DDI) (Cohort A1: Arm B)
Sofe-M administered IV and itraconazole administered orally
干预措施: Itraconazole (Drug)
Sofe-M (Combination Cohort A4)
Combination with bevacizumab administered IV
干预措施: bevacizumab (Drug)
Sofe-M Combination with Pembrolizumab (Dose-optimization Cohort A6)
Comparing 2 or more doses (evaluated during dose escalation) of Sofe-M administered IV with pembrolizumab
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY4170156
时间窗: 1 Cycle (21 days)
Number of participants with dose-limiting toxicities (DLTs)
Phase 1a: To determine the RP2D or optimal dose of LY4170156 with bevacizumab
时间窗: 1 Cycle (21 days)
Number of participants with DLTs
Phase 1a: To determine the RP2D or optimal dose of LY4170156 with carboplatin
时间窗: 1 Cycle (21 days)
Number of participants with DLTs
Phase 1b: To assess the antitumor activity of LY4170156 Monotherapy: Overall response rate (ORR)
时间窗: Up to Approximately 48 Months or 4 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Phase 1a: To determine the recommended phase 2 dose (RP2D) of Sofe-M (LY4170156)
时间窗: 1 Cycle (21 or 28 days)
Number of participants with dose-limiting toxicities (DLTs)
Phase 1a: To determine the RP2D or optimal dose of Sofe-M (LY4170156) with bevacizumab
时间窗: 1 Cycle (21 or 28 days)
Number of participants with DLTs
Phase 1a: To determine the RP2D or optimal dose of Sofe-M (LY4170156) with carboplatin
时间窗: 1 Cycle (21 or 28 days)
Number of participants with DLTs
Phase 1a: To determine the RP2D or optimal dose of Sofe-M (LY4170156) with pembrolizumab
时间窗: 1 Cycle (21 or 28 days)
Number of participants with DLTs
Phase 1b: To assess the antitumor activity of Sofe-M (LY4170156) Monotherapy: Overall response rate (ORR)
时间窗: Up to Approximately 60 Months or 5 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Phase 2: To assess the antitumor activity of Sofe-M (LY4170156) Monotherapy: ORR
时间窗: Up to Approximately 60 Months or 5 Years
ORR per RECIST 1.1
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Up to Approximately 60 Months or 5 Years
A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY4170156
时间窗: 1 Cycle (21 days)
Number of participants with dose-limiting toxicities (DLTs)
Phase 1a: To determine the RP2D or optimal dose of LY4170156 with bevacizumab
时间窗: 1 Cycle (21 days)
Number of participants with DLTs
Phase 1a: To determine the RP2D or optimal dose of LY4170156 with carboplatin
时间窗: 1 Cycle (21 days)
Number of participants with DLTs
Phase 1a: To determine the RP2D or optimal dose of LY4170156 with pembrolizumab
时间窗: 1 Cycle (21 days)
Number of participants with DLTs
Phase 1b: To assess the antitumor activity of LY4170156 Monotherapy: Overall response rate (ORR)
时间窗: Up to Approximately 48 Months or 4 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Up to Approximately 48 Months or 4 Years
A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module
次要结局
- To characterize the pharmacokinetics (PK) properties of LY4170156: Minimum Plasma Concentration (Cmin)(First 4 Cycles (84 days))
- To characterize the PK properties of LY4170156: Area under the concentration versus time curve (AUC)(First 4 Cycles (84 days))
- To evaluate the preliminary antitumor activity of LY4170156: Overall response rate (ORR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Duration of response (DOR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Time to response (TTR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Progression free survival (PFS)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Disease control rate (DCR)(Up to Approximately 48 Months or 4 Years)
- To characterize the pharmacokinetics (PK) properties of Sofe-M (LY4170156): Minimum Plasma Concentration (Cmin)(First 4 Cycles (84 days))
- To characterize the PK properties of Sofe-M (LY4170156): Cmin with bevacizumab or carboplatin(First 4 Cycles (Approximately 84 days))
- To characterize the PK properties of Sofe-M (LY4170156): Cmin with pembrolizumab(First 4 Cycles (84 days))
- To characterize the PK properties of Sofe-M (LY4170156): Area under the concentration versus time curve (AUC)(First 4 Cycles (84 days))
- To characterize the patient-reported outcomes (PRO) Common Terminology Criteria for Adverse Events (CTCAE) of Sofe-M (LY4170156)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Overall response rate (ORR)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Overall response rate (ORR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Duration of response (DOR)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Duration of response (DOR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Time to response (TTR)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Time to response (TTR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Progression free survival (PFS)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Progression free survival (PFS) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 60 Months or 5 Years])
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Disease control rate (DCR)(Up to Approximately 60 Months or 5 Years)
- To evaluate the preliminary antitumor activity of Sofe-M (LY4170156): Disease control rate (DCR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 60 Months or 5 Years)
- To characterize the pharmacokinetics (PK) properties of LY4170156: Minimum Plasma Concentration (Cmin)(First 4 Cycles (84 days))
- To characterize the PK properties of LY4170156: Cmin with bevacizumab or carboplatin(First 4 Cycles (Approximately 84 days))
- To characterize the PK properties of LY4170156: Cmin with pembrolizumab(First 4 Cycles (84 days))
- To characterize the PK properties of LY4170156: Area under the concentration versus time curve (AUC)(First 4 Cycles (84 days))
- To evaluate the preliminary antitumor activity of LY4170156: Overall response rate (ORR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Overall response rate (ORR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Duration of response (DOR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Duration of response (DOR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Time to response (TTR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Time to response (TTR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Progression free survival (PFS)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Progression free survival (PFS) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 48 Months or 4 Years])
- To evaluate the preliminary antitumor activity of LY4170156: Disease control rate (DCR)(Up to Approximately 48 Months or 4 Years)
- To evaluate the preliminary antitumor activity of LY4170156: Disease control rate (DCR) with bevacizumab or carboplatin or pembrolizumab(Up to Approximately 48 Months or 4 Years)