A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Tesaro, Inc.
- 入组人数
- 463
- 试验地点
- 1
- 主要终点
- Part 1: Number of participants with adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, treatment emergent adverse events (TEAEs), TEAEs leading to death and immune-related adverse events (irAEs)
研究概览
简要总结
This is a first-in-human study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022. The study will be conducted in 2 parts with Part 1 consisting of dose escalation and Part 2 dose expansion. Part 1 will determine the recommended Phase 2 dose (RP2D) of TSR-022 and Part 2 will evaluate the antitumor activity of TSR-022 in combination with TSR-042 or docetaxel and as monotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1a: TSR-022 monotherapy
干预措施: TSR-022 (Drug)
Part 1b: TSR-022 in combination with nivolumab
干预措施: TSR-022 (Drug)
Part 1b: TSR-022 in combination with nivolumab
干预措施: Nivolumab (Drug)
Part 1c: TSR-022 in combination with TSR-042
干预措施: TSR-022 (Drug)
Part 1c: TSR-022 in combination with TSR-042
干预措施: TSR-042 (Drug)
Part 1d: TSR-022 in combination with TSR-042 and TSR-033
干预措施: TSR-022 (Drug)
Part 1d: TSR-022 in combination with TSR-042 and TSR-033
干预措施: TSR-042 (Drug)
Part 1d: TSR-022 in combination with TSR-042 and TSR-033
干预措施: TSR-033 (Drug)
Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)
干预措施: TSR-022 (Drug)
Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)
干预措施: TSR-042 (Drug)
Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
干预措施: TSR-022 (Drug)
Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
干预措施: TSR-022 (Drug)
Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
干预措施: TSR-042 (Drug)
Part 1f: TSR-022 in combination with TSR-042 and Docetaxel
干预措施: Docetaxel (Drug)
Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
干预措施: TSR-022 (Drug)
Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
干预措施: TSR-042 (Drug)
Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
干预措施: Pemetrexed (Drug)
Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin
干预措施: Cisplatin (Drug)
Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
干预措施: TSR-042 (Drug)
Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
干预措施: Pemetrexed (Drug)
Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin
干预措施: Carboplatin (Drug)
Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042
干预措施: TSR-022 (Drug)
Part 2: Cohort A Melanoma-TSR-022 as monotherapy
干预措施: TSR-022 (Drug)
Part 2: Cohort A Melanoma-TSR-022 with TSR-042
干预措施: TSR-022 (Drug)
Part 2: Cohort A Melanoma-TSR-022 with TSR-042
干预措施: TSR-042 (Drug)
Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy
干预措施: TSR-022 (Drug)
Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042
干预措施: TSR-022 (Drug)
Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042
干预措施: TSR-042 (Drug)
Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy
干预措施: TSR-022 (Drug)
Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042
干预措施: TSR-042 (Drug)
Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042
干预措施: TSR-022 (Drug)
Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042
干预措施: TSR-042 (Drug)
Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel
干预措施: TSR-022 (Drug)
Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel
干预措施: Docetaxel (Drug)
Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042
干预措施: TSR-022 (Drug)
Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042
干预措施: TSR-042 (Drug)
结局指标
主要结局
Part 1: Number of participants with adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, treatment emergent adverse events (TEAEs), TEAEs leading to death and immune-related adverse events (irAEs)
时间窗: Up to 2 years
Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs)
时间窗: Up to 42 days
Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs)
时间窗: Up to 21 days
Part 1: Number of participants with clinically significant changes in laboratory parameters, vital signs, electrocardiogram (ECG) findings, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications
时间窗: Up to 2 years
Part 1 (e) and Part 2: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
时间窗: Up to 2 years
Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs)
时间窗: Up to 28 days
次要结局
- Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 2F: Percent change from Baseline in Alpha-fetoprotein (AFP)(Baseline, and up to 2 years)
- Part 2 (A, B, C, D, F): Serum concentration of TSR-042(Up to 2 years)
- Part 2 (A, B, C, D): DCR by irRECIST(Up to 2 years)
- Part 2F: Cmin of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1b: AUC (0-last) of TSR-022 in combination with nivolumab(Up to 2 years)
- Part 1c: AUC (0-last) of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1b: t1/2 of TSR-022 and in combination with nivolumab(Up to 2 years)
- Part 1a: Area under the concentration × time curve from time 0 to infinity AUC (0-inf) of TSR-022 as monotherapy(Up to 2 years)
- Part 2 (A, B, C, D): DOR by irRECIST(Up to 2 years)
- Part 2: Progression-free survival (PFS) by RECIST v 1.1(Up to 2 years)
- Part 2: Overall survival (OS)(Up to 2 years)
- Part 1a: Terminal half life (t 1/2) of TSR-022 as monotherapy(Up to 2 years)
- Part 1c: t1/2 of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1d: AUCtau of TSR-022 in combination with TSR-042 and TSR-033(Up to 2 years)
- Part 2F: Number of participants with AEs, SAEs, AEs leading to discontinuation, TEAEs, TEAEs leading to death(Up to 2 years)
- Part 2: Duration of response (DOR) by RECIST v 1.1(Up to 2 years)
- Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1(Up to 2 years)
- Part 2 (A, B, C, D): PFS by irRECIST(Up to 2 years)
- Parts 1 and 2 (A, B, C, D, E, F): Serum concentration of TSR-022(Up to 2 years)
- Part 1d: Serum concentration of TSR-033(Up to 2 years)
- Part 1 (c, d, e, f, g, h): Serum concentration of TSR-042(Up to 2 years)
- Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033(Up to 2 years)
- Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy(Up to 2 years)
- Part 1b: Cmin of TSR-022 in combination with nivolumab(Up to 2 years)
- Part 1c: Cmin of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1(Up to 2 years)
- Part 2 (A, B, C, D): ORR by Immune related RECIST (irRECIST)(Up to 2 years)
- Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab(Up to 2 years)
- Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033(Up to 2 years)
- Part 2F: AUC (0-inf) of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 2F: AUC (0-last) of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1: Number of participants with anti-drug antibodies (ADAs) to TSR-022(Up to 2 years)
- Part 2 (A, B, C, D, E, F): Number of participants with ADA to anti-TSR-022(Up to 2 years)
- Part 1d: Number of participants with ADA to TSR-033(Up to 2 years)
- Part 1a: Area under the concentration time curve from time 0 to last assessment (AUC 0-last) of TSR-022 as monotherapy(Up to 2 years)
- Part 2F: t1/2 of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1c: AUCtau of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 2F: AUCtau of TSR-022 in combination with TSR-042(Up to 2 years)
- Part 1 (c, d, e, f, g, h): Number of participants with ADA to TSR-042(Up to 2 years)
- Part 1d: AUC (0-last) of TSR-022 in combination with TSR-042 and TSR-033(Up to 2 years)
- Part 1d: t1/2 of TSR-022 in combination with TSR-042 and TSR-033(Up to 2 years)
- Part 1a: Area under the concentration × time curve during the dosing interval (AUCtau) of TSR-022 as monotherapy(Up to 2 years)
- Part 1b: AUCtau of TSR-022 and in combination with nivolumab(Up to 2 years)
- Part 2 (A, B, C, D, F): Number of Participants with ADA to TSR-042(Up to 2 years)