A Phase 2 Study of ALKS 4230 in Combination With Anti-PD-1 (Pembrolizumab) in Patients With Advanced or Recurrent Head and Neck Squamous Cell Cancer Currently on Treatment With Anti-PD-(L)1 Without Having Achieved a Complete Remission
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) Based on RECIST v1.1
研究概览
简要总结
The primary objective of this study was to estimate the response rate to ALKS 4230 in combination with pembrolizumab in patients with HNSCC who had previously received anti-PD-(L)1 therapy but who had not achieved a CR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Patients must have histologically or cytopathologically confirmed diagnosis of non-cutaneous squamous cell carcinoma of the head and neck region that is locally advanced and/or recurrent and no longer amenable to local surgical or radiation therapy and/or with evidence of distant metastatic disease
- •Patients must have had anti-PD-(L)1 therapy as the most recent systemic therapy with either stable disease or partial response on prior anti-PD-(L)1 therapy, or progressive disease on prior anti-PD-(L)1 therapy
- •Patients must have disease that is measurable by RECIST v1.1
- •Patients must be willing to provide tumor tissue biopsy
- •Patients must demonstrate adequate organ function
- •Female patients of childbearing potential should have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication
- •Patients must agree to follow contraceptive requirements defined in the protocol
- •Additional criteria apply
排除标准
- •Patient is pregnant or breastfeeding or expecting to conceive or father children
- •Patient has an active major infection requiring systemic therapy within 1 week of starting study drug
- •Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate, provided that they are stable, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study drug
- •Patient has hypersensitivity to pembrolizumab, ALKS 4230, or any of their excipients
- •Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (inhaled or topical steroids and steroid replacement at physiologic doses are allowable)
- •Patient has prior Grade ≥3 immune-related toxicities requiring systemic immunosuppressant treatment that were attributable or possibly attributable to PD-1 immune checkpoint blockade
- •Patient has active tuberculosis or known active infection with hepatitis B or hepatitis C
- •Patient has known psychiatric or substance abuse disorders or a social situation that would interfere with cooperation with the requirements of the study
- •Additional criteria apply
研究组 & 干预措施
Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg
Participants with current stable disease (SD) or partial response (PR) (Cohorts 1 and 2) who were not progressing or further demonstrating reductions in tumor size were to receive nemvaleukin alfa 3 microgram per kilogram (mcg/kg), intravenous (IV) infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 milligram (mg), IV infusion, once, every three weeks (Q3W) on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation.
干预措施: Nemvaleukin Alfa (Drug)
Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg
Participants with current stable disease (SD) or partial response (PR) (Cohorts 1 and 2) who were not progressing or further demonstrating reductions in tumor size were to receive nemvaleukin alfa 3 microgram per kilogram (mcg/kg), intravenous (IV) infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 milligram (mg), IV infusion, once, every three weeks (Q3W) on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation.
干预措施: Pembrolizumab (Drug)
Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with progressive disease (PD) (Cohorts 3 and 4) received nemvaleukin alfa 3 mcg/kg, IV infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 mg, IV infusion, once, Q3W on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation.
干预措施: Nemvaleukin Alfa (Drug)
Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with progressive disease (PD) (Cohorts 3 and 4) received nemvaleukin alfa 3 mcg/kg, IV infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 mg, IV infusion, once, Q3W on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Overall Response Rate (ORR) Based on RECIST v1.1
时间窗: From the first dose of study drug until first PD or death, whichever occurred first (up to 49 weeks)
ORR was defined as percentage of participants with complete response (CR) or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
次要结局
- Duration of Response (DOR) Based on RECIST v1.1(From first documented CR or PR until first documentation of PD (up to 49 weeks))
- Progression-free Survival (PFS) Based on RECIST v1.1(From the first dose of study drug to date of PD, start of alternate therapy or death, whichever occurred first (up to 49 weeks))
- Time to Progression (TTP) Based on RECIST v1.1(From first dose of study drug to the date of the first documentation of PD (up to 49 weeks))
- Disease Control Rate (DCR) Based on RECIST v1.1(From first dose of study drug until PD or death, whichever occurred first (up to 49 weeks))
- Overall Survival (OS)(From date of first dose of study drug up to death from any cause (up to 89 weeks))
- Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks))
- Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment(From first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks))