A Phase 2, Open-label Study of Amivantamab in Subjects With Previously Treated Advanced or Metastatic Gastric or Esophageal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 62
- 试验地点
- 10
- 主要终点
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
研究概览
简要总结
The purpose of this study is to investigate the activity of amivantamab in gastric cancer (GC) and esophageal cancer (EC) participants (Phase 2a), and to characterize the preliminary antitumor activity of amivantamab in selected GC and EC population (Phase 2b).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must have histologically or cytologically confirmed gastric (including gastroesophageal junction [GEJ]) or esophageal cancer (EC) that is locally advanced, unresectable, or metastatic, and not eligible for curative treatment
- •Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.
- •If only 1 measurable lesion exists, it may be used for the screening biopsy if the baseline tumor assessment scans are performed greater than or equal to (>=) 7 days after the biopsy
- •Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Gastric or GEJ Cancer Only - Must be refractory or ineligible to at least 2 prior lines of standard of care systemic therapy. Prior therapies must include fluoropyrimidine- and platinum-based chemotherapy. Participants with known human epidermal growth factor receptor (HER) 2 expression must have had HER2 targeting therapy as part of the prior therapy
- •Esophageal Cancer Only
- •Must be refractory or intolerant to at least 1 prior line of systemic therapy. Prior therapies must include fluoropyrimidine-, and platinum-based chemotherapy (including chemoradiation therapy given as stage intravenous [IV] setting)
排除标准
- •Participant has an uncontrolled illness, including but not limited to the following: diabetes; ongoing or active bacterial infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week before enrollment]), symptomatic viral infection, or any other clinically significant infection; active bleeding diathesis and psychiatric illness/social situation that would limit compliance with study requirements
- •Participant has received prior epidermal growth factor receptor (EGFR) or tyrosine-protein kinase mesenchymal-epithelial transition (cMet)-directed therapies
- •Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer or had radiation therapy within 4 weeks before the first administration of study treatment. For agents with long half-lives, the maximum required time since last dose is 28 days. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia or post-radiation skin changes [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement)
- •Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to the first administration of study treatment is eligible), history of leptomeningeal disease or spinal cord compression that has not been treated definitively with surgery or radiation. If brain metastases are diagnosed on screening imaging, the participant may be rescreened for eligibility after definitive treatment
- •Participant has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Esophageal cancer participants with history of completely resolved radiation pneumonitis (defined as radiographically stable for 3 months prior to enrollment without need of any treatment) may be enrolled
研究组 & 干预措施
Amivantamab: Gastric Cancer (GC) Cohorts
Participants in Phase 2a GC cohorts will receive intravenous (IV) infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight less than (<) 80 kilograms (kg) will receive IV infusion of amivantamab 1,050 milligrams (mg) and participants with body weight greater than or equal to (>=) 80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle), followed by additional dosing based on body weight if recommended by clinical trial management team (CTMT) (amivantamab 1750 mg for body weight <80 kg and 2100 mg for body weight >=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b GC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.
干预措施: Amivantamab (Drug)
Amivantamab: Esophageal Cancer (EC) Cohorts
Participants in Phase 2a EC cohorts will receive IV infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight <80 kg will receive IV infusion of amivantamab 1,050 mg and participants with body weight >=80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle) followed by additional dosing based on body weight if recommended by CTMT (amivantamab 1750 mg for body weight <80 kg and 2100 mg for body weight >=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b EC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.
干预措施: Amivantamab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
时间窗: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
ORR was defined as the percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) as determined by investigator per RECIST version 1.1. As per RECIST version 1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<)10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression.
次要结局
- Disease Control Rate (DCR) Per RECIST Version 1.1(From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months))
- Duration of Response (DOR) as Per RECIST Version 1.1(From the date of first documented response up to date of first documented PD or death (up to 9 months))
- Time to Response (TTR) as Per RECIST Version 1.1(From first dose of study treatment until first documentation of CR or PR (up to 9 months))
- Progression Free Survival (PFS) as Per RECIST Version 1.1(From day of first dose (Day 1) until PD or death (up to 9 months))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0(From start of the treatment (Day 1) up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (up to 9 months))
- Maximum Observed Serum Concentration (Cmax) for Amivantamab(Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab(Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab(Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1 (each cycle was of 28 days))
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab(Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab(Pre-dose at 0 hour: Days 8 and 15 of Cycle 1; Days 1 and 15 of Cycles 2, 3 and 4; Day 1 of Cycles 6 and 8 (each cycle was of 28 days))
- Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab(Pre-dose at 0 hour: Day 15 of Cycle 1; Days 1 and 15 of Cycles 2 and 3; Day 1 of Cycles 6 and 8 (each cycle was of 28 days))
- Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for Amivantamab(Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for Amivantamab(Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Apparent Clearance at Steady State (CLss) of Amivantamab(Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Apparent Volume of Distribution at Steady State (Vss) of Amivantamab(Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Accumulation Ratio (AR) of AUCtau for Amivantamab(Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days))
- Number of Participants With Anti-Amivantamab Antibodies(From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months))