A Multicenter, Randomized, Double-Blind, Phase 2, Basket Study of MK-4280A, a Coformulation of Favezelimab (MK-4280) With Pembrolizumab (MK-3475) in Selected Solid Tumors (KeyForm-010)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 54
- 主要终点
- Clinical Benefit Rate - Cohort A
研究概览
简要总结
The purpose of this study is to evaluate pathologic complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as assessed by blinded central pathology review (BICR) in participants with cutaneous squamous cell carcinoma (cSCC) [Cohort A] and to evaluate lenvatinib in combination with coformulated favezelimab/pembrolizumab or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator in participants proficient in mismatch repair (pMMR) endometrial cancer (EC) [Cohort B].
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Cohort A only
- •Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
- •Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in the head and neck will be staged according to American Joint Committee on Cancer (AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will be staged according to Union for International Cancer Control (UICC) Ed. 8
- •Is systemic treatment naïve
- •Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided
- •Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent
- •Cohort B only
- •Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a local test report
- •Documented evidence of stage IVB (per 2009 International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation
- •Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting
- •Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention)
- •Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent
- •Has adequately controlled blood pressure without antihypertensive medication
- •All Cohorts
- •Agrees to follow contraception guidelines if a participant of childbearing potential
- •Has a life expectancy >3 years per investigator assessment
- •Has adequate organ function
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and undetectable viral load prior to randomization
- •If positive for hepatitis C, has undetectable viral load at screening
- •If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy
排除标准
- •All Cohorts
- •Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monoclonal antibody (mAb)
- •History of allogeneic tissue/solid organ transplant
- •Cohort A only
- •Received prior radiotherapy to the index lesion (in-field lesion)
- •Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible
- •Has had major surgery within 3 weeks prior to first dose of study interventions
- •Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
- •Has urine protein ≥1 g/24 hours
- •Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO)
- •Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
研究组 & 干预措施
Favezelimab/Pembrolizumab
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.
干预措施: favezelimab/pembrolizumab (Biological)
Pembrolizumab
Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.
干预措施: pembrolizumab (Biological)
Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
干预措施: favezelimab/pembrolizumab (Biological)
Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
干预措施: lenvatinib (Drug)
Pembrolizumab + Lenvatinib (Cohort B)
Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
干预措施: pembrolizumab (Biological)
Pembrolizumab + Lenvatinib (Cohort B)
Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
干预措施: lenvatinib (Drug)
结局指标
主要结局
Clinical Benefit Rate - Cohort A
时间窗: Up to approximately 22 months
Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as major pathologic response (mPR) or pCR in participants who undergo surgery, or clinical complete response (cCR) \[defined as residual tumor not visible on clinical exam nor on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B
时间窗: Up to approximately 21 months
The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as 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) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
次要结局
- Pathologic Complete Response (pCR) - Cohort A(Up to approximately 22 months)
- Major Pathologic Response (mPR) - Cohort A(Up to approximately 22 months)
- ORR per RECIST 1.1 as assessed by Investigator - Cohort A(Up to approximately 22 months)
- Number of participants with an adverse event (AE) - Cohorts A and B(Up to approximately 41 months)
- Number of participants discontinuing from study therapy due to AE - Cohorts A and B(Up to approximately 41 months)
- Number of participants experiencing perioperative complications - Cohort A(Up to approximately 18 weeks)
- Number of participants with an AE that precludes surgery - Cohort A(Up to approximately 2 months)