A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tarlatamab in Combination With ZL-1310 With or Without Anti-PD-L1 in Participants With Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 160
- 试验地点
- 27
- 主要终点
- Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objective of this trial is to evaluate the safety and tolerability of tarlatamab in combination with ZL-1310 with or without durvalumab and to determine the maximum tolerated combination dose (MTCD) and/or recommended phase 2 dose (RP2D) of ZL-1310 in combination with tarlatamab.
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
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
- •Participants with Histologically or cytologically confirmed SCLC:
- •For Part 1, participants must have SCLC that has progressed or recurred following at least 1 line of platinum-based anti-cancer therapy.
- •For Parts 1 and 2, participants must have progressed or recurred following at least 1 line of platinum-based therapy. No prior tarlatamab is allowed in Cohort 2-
- •For Part 3, participants must have extensive-stage SCLC (ES-SCLC) with no prior systemic treatment other than 1 cycle of platinum-based chemotherapy.
- •Note: Participants with prior treatment for limited-stage SCLC (LS-SCLC) before diagnosis of ES SCLC are permitted.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •At least 1 measurable lesion as defined per RECIST v1.1 within 21-day screening period, not previously irradiated.
- •Adequate organ function (hematological, coagulation, renal, hepatic, pulmonary, and cardiac function).
排除标准
- •Symptomatic CNS metastases. Participants with treated brain metastases are eligible provided they meet the criteria specified in the protocol.
- •History of interstitial lung disease (ILD)/pneumonitis.
- •Received thoracic radiation therapy within 90 days prior to first dose of trial intervention.
- •Prior therapy with any delta-like ligand 3 (DLL3)-directed therapy.
- •Prior exposure to topoisomerase I inhibitors or antibody-drug conjugate (ADC) with topoisomerase I inhibitor payload.
- •Receiving strong CYP3A4 or CPY2D6 inhibitors within 14 days or 5 half-lives (whichever is longer) before the first dose of trial treatment.
- •Enrollment in any tarlatamab clinical trial.
研究组 & 干预措施
Triplet Combination (Part 3)
ZL-1310 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (durvalumab) each administered IV.
干预措施: Tarlatamab (Drug)
Triplet Combination (Part 3)
ZL-1310 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (durvalumab) each administered IV.
干预措施: ZL-1310 (Drug)
Dose Exploration (Part 1)
Multiple dose levels of ZL-1310 will be explored in combination with tarlatamab administered intravenously (IV).
干预措施: Tarlatamab (Drug)
Dose Expansion (Part 2)
ZL-1310 will be administered IV at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV.
干预措施: Tarlatamab (Drug)
Dose Exploration (Part 1)
Multiple dose levels of ZL-1310 will be explored in combination with tarlatamab administered intravenously (IV).
干预措施: ZL-1310 (Drug)
Triplet Combination (Part 3)
ZL-1310 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (durvalumab) each administered IV.
干预措施: Durvalumab (Drug)
Dose Expansion (Part 2)
ZL-1310 will be administered IV at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV.
干预措施: ZL-1310 (Drug)
结局指标
主要结局
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 3.5 years
Parts 1 and 3: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
时间窗: Up to Day 21
次要结局
- Duration of Response (DOR) per RECIST v1.1(Up to 3.5 years)
- Time to Response (TTR) per RECIST v1.1(Up to 3.5 years)
- Disease Control Rate (DCR) per RECIST v1.1(Up to 3.5 years)
- Progression-free Survival (PFS) per RECIST v1.1(Up to 3.5 years)
- Time to Progression (TTP) per RECIST v1.1(Up to 3.5 years)
- Time to Subsequent Therapy(Up to 3.5 years)
- Overall survival (OS)(Up to 3.5 years)
- Serum Tarlatamab Concentrations(Up to Week 36)
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(Up to 3.5 years)