A Phase 1b Study Evaluating the Safety and Efficacy of AMG 757 in Combination With AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 23
- 试验地点
- 17
- 主要终点
- Part 1: Number of Participants Who Experienced Dose-limiting Toxicity (DLT)
研究概览
简要总结
The main purpose of this study is to evaluate the safety, tolerability, and recommended phase 2 target dose of tarlatamab in combination with AMG 404.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
- •Age greater than or equal to 18 years old at the same time of signing the informed consent
- •Participants with histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) who progressed or recurred following at least 1 platinum-based regimen
- •Eastern Cooperative Oncology Group (ECOG) 0 to 1
- •Participants with treated brain metastases are eligible provided they meet defined criteria
- •Adequate organ function as defined in protocol
排除标准
- •History of other malignancy within the past 2 years with exceptions
- •Major surgery within 28 days of first dose of tarlatamab
- •Untreated or symptomatic brain metastases and leptomeningeal disease
- •Prior anti-cancer therapy, including anti-PD1 or anti-PDL1 antibody therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and the first planned dose of tarlatamab
- •Exceptions:
- •Participants who received prior chemotherapy must have completed at least 14 days before the first dose of tarlatamab and all treatment-related toxicity resolved to grade ≤
- •Participants who received prior palliative radiotherapy must have completed at least 7 days before the first dose of tarlatamab
- •Participants who received prior tarlatamab therapy or prior delta-like ligand 3 (DLL3) x cluster of differentiation 3 (CD3) bispecific therapy are not eligible
- •Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents
- •History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis
- •Participants with evidence of interstitial lung disease or active, non-infectious pneumonitis
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab
- •History of solid organ transplantation
- •History of hypophysitis or pituitary dysfunction
- •Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted
研究组 & 干预措施
Phase 1: Dose Exploration
The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).
干预措施: Tarlatamab (Drug)
Phase 1: Dose Exploration
The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).
干预措施: AMG 404 (Drug)
Phase 2: Dose Expansion
Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.
干预措施: Tarlatamab (Drug)
Phase 2: Dose Expansion
Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.
干预措施: AMG 404 (Drug)
结局指标
主要结局
Part 1: Number of Participants Who Experienced Dose-limiting Toxicity (DLT)
时间窗: First dose of tarlatamab up to 28 days
A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events v4.0: * Grade 3 adverse event (AE) except for fatigue lasting \< 7 days, Grade 3 nonfebrile neutropenia that improved to ≤ Grade 1 within 3 weeks, endocrinopathies if managed with replacement therapy, Grade 3 nausea/vomiting or diarrhea for \< 72 hours, Grade 3 amylase or lipase values not associated with pancreatitis, Grade 3 hematologic laboratory abnormalities not clinically relevant, or Grade 3 electrolyte abnormality up to 72 hours. * Grade 4 AE except for Grade 4 nonfebrile neutropenia lasting ≤ 7 days, Grade 4 electrolyte abnormality lasting up to 72 hours, Grade 4 amylase or lipase values not associated with pancreatitis, or Grade 4 hematologic laboratory abnormalities no clinically relevant. * Grade 5 AE * Recurrent Grade ≥ 2 pneumonitis * Any other toxicity requiring permanent discontinuation of AMG 404.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Any TEAEs: From first IP dose up to last dose + 65 days or EOS, median duration was 4.2 months; TEAEs for EP: From last dose + 65 days up to snapshot date (15 November 2024), death, or last dose + 145 days or EOS, median duration was 2.6 months
An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (IP; tarlatamab) up to 65 days after the last dose of tarlatamab or AMG 404 or the end of study (EOS), whichever was earlier. A TEAE for the EP was an AE that occurred after the 65th day after the last dose of tarlatamab or AMG 404 up to 145 days after the last dose of tarlatamab or AMG 404 or end of study, whichever was later. A treatment-related AE was any TEAE where there was a reasonable possibility that the TEAE could have been caused by tarlatamab or AMG 404. Any clinically significant changes in vital signs, physical examinations, electrocardiograms, and clinical laboratory tests were included as TEAEs.
次要结局
- Objective Response Rate Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months)
- Duration of Response Per Modified RECIST v1.1(From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months)
- Disease Control Rate Per Modified RECIST v1.1(From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months)
- Progression-free Survival Per Modified RECIST v1.1(From first dose of IP up to a minimum of EOS or death; median (min, max) time was 9.4 (0.4, 25.5) months)
- Overall Survival(From first dose of IP up to a minimum of EOS or death; median (min, max) time was 9.4 (0.4, 25.5) months)
- Maximum Observed Concentration (Cmax) of Tarlatamab in Combination With AMG 404(Cycle 2 Day 1 (pre-dose up to 7 days post-dose); Cycle 2 Day 15 (pre-dose up to 14 days post-dose))
- Trough Concentration (Ctrough) of Tarlatamab in Combination With AMG 404(Cycle 2 Day 15 (pre-dose))
- Area Under the Concentration-time Curve From Time 0 to 336 Hours (AUC0-336) of Tarlatamab in Combination With AMG 404(Cycle 2 Day 1 (pre-dose up to 7 days post-dose); Cycle 2 Day 15 (pre-dose up to 14 days post-dose))