A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02C
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 146
- 试验地点
- 58
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has histologically or cytologically confirmed melanoma
- •Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
- •Has been untreated for Stage IIIB, IIIC or IIID melanoma
- •Surgical resection and re-resection of primary melanoma is allowed
- •Prior radiotherapy to the primary melanoma is allowed
- •Has provided a baseline tumor biopsy
- •Male participants who receive gebasaxturev are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of gebasaxturev
- •Male participants who receive all-trans retinoic acid (ATRA) are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of ATRA
- •Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, vibostolimab, gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last dose of ATRA, whichever occurs last
- •Has adequate organ function
- •Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
排除标准
- •Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
- •Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
- •Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has ocular or mucosal melanoma
- •Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has an active infection requiring systemic therapy
- •Has known history of human immunodeficiency virus (HIV)
- •Has known history of hepatitis B
- •Has a history of (noninfectious) pneumonitis
- •Has a history of active tuberculosis (TB)
- •Has received prior systemic anticancer therapy within 4 weeks prior to randomization
- •Has received prior radiotherapy within 2 weeks of first dose of study intervention
- •Has had major surgery <3 weeks prior to first dose of study intervention
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
- •Has had an allogeneic tissue/solid organ transplant
- •Has only mucosal lesions
- •Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses
研究组 & 干预措施
Pembrolizumab + Vibostolimab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Vibostolimab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Vibostolimab (Biological)
Pembrolizumab + Gebasaxturev
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus gebasaxturev (V937) intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Gebasaxturev
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus gebasaxturev (V937) intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Gebasaxturev (Biological)
Pembrolizumab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + MK-4830
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus MK-4830 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + MK-4830
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus MK-4830 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: MK-4830 (Biological)
Favezelimab + Pembrolizumab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive MK-4280A (favezelimab and pembrolizumab administered as a co-formulation) IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Favezelimab + Pembrolizumab (Biological)
Pembrolizumab + all-trans retinoic acid (ATRA)
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + all-trans retinoic acid (ATRA)
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
干预措施: ATRA (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: Up to ~1.5 months
pCR rate is defined as the proportion of participants with complete absence of viable tumor in the treated tumor bed. Assessments are according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Percentage of participants who experience an adverse event (AE)
时间窗: Up to ~16 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
Percentage of participants who discontinue study treatment due to an AE
时间窗: Up to ~12 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
Pathological Complete Response (pCR) Rate With 90% Confidence Interval (CI)
时间窗: Up to approximately 6 weeks
pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 90% CI was reported.
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 17 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE was reported.
Percentage of Participants Who Discontinued Study Intervention Due to an AE
时间窗: Up to approximately 13 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported.
pCR Rate With 95% CI
时间窗: Up to approximately 6 weeks
pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 95% CI was reported.
次要结局
- Near pathological complete response (near pCR) rate(Up to ~1.5 months)
- Pathological partial response (pPR) rate(Up to ~1.5 months)
- Recurrence-free survival (RFS)(Up to ~60 months)
- Near pCR Rate With 90% CI(Up to approximately 6 weeks)
- Near pCR Rate With 95% CI(Up to approximately 6 weeks)
- Pathological Partial Response (pPR) Rate With 90% CI(Up to approximately 6 weeks)
- pPR Rate With 95% CI(Up to approximately 6 weeks)
- Recurrence-Free Survival (RFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by The Investigator(Up to approximately 62 months)