NCT04704219已完成2 期
A Phase 2, Single-arm, Open-label Clinical Trial of Pembrolizumab Plus Lenvatinib in Participants With First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (nccRCC) (KEYNOTE-B61)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 56
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This study is being performed as a single-arm open-label study in order to rapidly provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with previously untreated advanced/metastatic non-clear cell renal cell carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have a histologically confirmed diagnosis of nccRCC.
- •Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer).
- •Has received no prior systemic therapy for advanced nccRCC. Note: Prior neoadjuvant/adjuvant therapy for nccRCC is acceptable if completed >12 months prior to allocation.
- •Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of study medication, or refrain from heterosexual intercourse during this period.
- •Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last.
- •Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- •Has Karnofsky Performance Status (KPS) ≥70% as assessed within 10 days prior to the start of study intervention.
- •Has adequately controlled blood pressure with or without antihypertensive medications
- •Have adequate organ function.
排除标准
- •Has collecting duct histology.
- •A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.
- •Has a left ventricular ejection fraction below the institutional (or local laboratory) normal range.
- •Has radiographic 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.
- •Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
- •Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
- •Has had major surgery within 3 weeks prior to first dose of study intervention.
- •Has received prior therapy with an anti-programmed cell-death 1 (PD-1), anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to allocation.
- •Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- •Has received a live or attenuated vaccine within 30 days before the first dose of study intervention.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has an active infection requiring systemic therapy.
- •Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- •Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus.
- •Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
- •Has had an allogenic tissue/solid organ transplant.
研究组 & 干预措施
Pembrolizumab + Lenvatinib
Experimental
Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation PLUS Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Lenvatinib
Experimental
Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation PLUS Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to approximately 47 months
ORR was defined as the percentage of participants who had a best overall response of either 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 as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR as assessed per RECIST 1.1 by blinded independent central review (BICR) is presented.
次要结局
- Duration of Response (DOR)(Up to approximately 47 months)
- Progression Free Survival (PFS)(Up to approximately 47 months)
- Overall Survival (OS)(Up to approximately 47 months)
- Clinical Benefit Rate (CBR)(Up to approximately 47 months)
- Disease Control Rate (DCR)(Up to approximately 47 months)
- Number of Participants With One or More Adverse Events (AEs)(Up to approximately 56 months)
- Number of Participants Who Discontinued From Study Treatment Due to an AE(Up to approximately 56 months)
研究者
研究点 (56)
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相关资讯
Advancements in Renal Cell Carcinoma Treatment: Immunotherapy Combinations and Personalized Approaches- Immunotherapy-based combinations are increasingly prevalent in first-line treatment for advanced renal cell carcinoma (RCC), offering personalized options.
- Long-term data from trials like CheckMate 214 and CheckMate 9ER confirm the sustained benefits of nivolumab-based combinations in RCC.
- Biomarker analysis from the CLEAR study indicates that pembrolizumab plus lenvatinib demonstrates superior efficacy compared to sunitinib across various subgroups.
- Research is expanding to non-clear cell RCC, with studies like PAPMET and KEYNOTE-B61 exploring immunotherapy's role in these less common subtypes.last yearIO/TKI Combinations Show Promise in Non-Clear Cell Renal Cell Carcinoma- Pembrolizumab plus lenvatinib demonstrated a 50% overall response rate in treatment-naive non-clear cell RCC, leading to FDA approval and NCCN recommendation.
- Cabozantinib plus nivolumab showed a 54% overall response rate in a phase 2 trial, supporting its use in non-clear cell RCC, even with prior therapy in some patients.
- Both IO/TKI combinations exhibit manageable adverse event profiles, with common toxicities including hypertension, diarrhea, and hand-foot syndrome.
- Dose adjustments and interruptions are crucial for managing toxicities and maintaining patients on treatment, potentially improving long-term outcomes.last yearIO/TKI Doublets Emerge as Standard of Care in Non-Clear Cell Renal Cell Carcinoma- Phase 2 trials show that IO/TKI combinations, like lenvatinib plus pembrolizumab, demonstrate efficacy in non-clear cell renal cell carcinoma (non-ccRCC) with manageable safety profiles.
- KEYNOTE-B61 trial reported a 51% objective response rate (ORR) in non-ccRCC patients treated with lenvatinib and pembrolizumab, supporting NCCN guideline recommendations.
- Cabozantinib plus nivolumab also shows promise, with a 48% ORR in a phase 2 trial, establishing IO/TKI doublets as effective first-line options for non-ccRCC.
- Treatment decisions should consider patient preference and individual data interpretation, according to Dr. Moshe Ornstein from Cleveland Clinic.2 years ago