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 02A
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 36
- 主要终点
- Percentage of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
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 unresectable Stage III or Stage IV melanoma, not amenable to local therapy
- •Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
- •Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
- •Has not received more than 3 lines of therapy for their advanced melanoma
- •Has provided a tumor biopsy
- •Male participants who receive lenvatinib or 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 lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed
- •Female participant 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, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or 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 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 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 a pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula
- •Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation
- •Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
研究组 & 干预措施
Pembrolizumab + Quavonlimab + Lenvatinib
Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Quavonlimab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Quavonlimab (Biological)
Pembrolizumab + Quavonlimab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Vibostolimab (Biological)
Pembrolizumab + Quavonlimab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + all-trans retinoic acid (ATRA)
Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years
干预措施: ATRA (Drug)
Pembrolizumab + Quavonlimab + Lenvatinib
Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Lenvatinib (Drug)
Pembrolizumab + all-trans retinoic acid (ATRA)
Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Quavonlimab + Lenvatinib
Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Quavonlimab (Biological)
结局指标
主要结局
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 39 months
An AE was 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 is reported.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to 35 months
An AE was 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 treatment due to an AE is reported.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) With 95% Confidence Interval (CI)
时间窗: Up to approximately 59 months
ORR was defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 95% CI was reported.
ORR Per RECIST 1.1 With 90% CI
时间窗: Up to approximately 59 months
ORR was defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 90% CI was reported.
次要结局
- Duration of Response (DOR) Per RECIST 1.1(Up to approximately 59 months)