NCT06345729招募中3 期
A Phase 3, Randomized, Double-blind, Multicenter Study of MK-1084 in Combination With Pembrolizumab Compared With Pembrolizumab Plus Placebo as Firstline Treatment of Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic NSCLC With PD-L1 TPS ≥50% (KANDLELIT-004)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 430
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses:
Hypothesis 1: Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).
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
- •The main inclusion and
排除标准
- •include but are not limited to the following:
- •Inclusion Criteria:
- •Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
- •Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
- •Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
- •If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline
- •If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
- •If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
- •If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable
- •Exclusion Criteria:
- •Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
- •Has known history of, or active, neurologic paraneoplastic syndrome
- •Has an active infection requiring systemic therapy, with exceptions
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease
- •Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC
- •Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
- •Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis
- •Has known active central nervous system metastases and/or carcinomatous meningitis
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has active autoimmune disease that has required systemic treatment in the past 2 years
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has history of allogenic tissue/solid organ transplant
- •Has not fully recovered from any effects of major surgical procedure
研究组 & 干预措施
Placebo with Pembrolizumab
Active Comparator
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
干预措施: Placebo (Other)
Placebo with Pembrolizumab
Active Comparator
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
干预措施: Pembrolizumab (Biological)
Calderasib with Pembrolizumab
Experimental
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.
干预措施: Calderasib (Drug)
Calderasib with Pembrolizumab
Experimental
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 42 months
PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
时间窗: Up to approximately 56 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- Number of Participants Who Experience One or More Adverse Event (AEs)(Up to approximately 56 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score(Baseline and Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 42 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score(Baseline and Up to approximately 24 months)
- Objective Response Rate (ORR)(Up to approximately 42 months)
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)(Up to approximately 56 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Chest pain (Item 40) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) Chest pain (Item 40) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score(Baseline and Up to approximately 24 months)
研究者
研究点 (430)
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相关资讯
Merck Launches Phase 3 KANDLELIT-007 Trial for Calderasib-KEYTRUDA QLEX Combination in KRAS G12C-Mutant Lung Cancer- Merck has initiated KANDLELIT-007, a Phase 3 trial evaluating calderasib (MK-1084) combined with KEYTRUDA QLEX for first-line treatment of KRAS G12C-mutant nonsquamous non-small cell lung cancer.
- The randomized trial will enroll approximately 675 patients globally, comparing the chemotherapy-free oral/subcutaneous combination against standard KEYTRUDA QLEX plus chemotherapy.
- This marks the third Phase 3 study in Merck's KANDLELIT program investigating calderasib across multiple KRAS G12C-mutant cancer types and treatment settings.
- The KRAS G12C mutation occurs in approximately 4% to 14% of lung cancer patients globally, representing a significant unmet medical need in oncology.8 months agoMerck Launches Phase 3 Trial of MK-1084 Plus Pembrolizumab for KRAS G12C-Mutated NSCLC- Merck has initiated a phase 3 trial evaluating MK-1084, an investigational oral KRAS G12C inhibitor, in combination with pembrolizumab as first-line treatment for metastatic NSCLC patients with KRAS G12C mutations and PD-L1 expression ≥50%.
- The double-blind, multicenter trial will enroll approximately 600 patients globally, with primary endpoints of progression-free survival and overall survival.
- Phase 1 data showed promising efficacy with a 47% overall response rate for the combination therapy compared to 19% for MK-1084 monotherapy.
- KRAS G12C is the most common KRAS mutation in NSCLC patients, occurring in approximately 14% of adenocarcinomas, representing a significant unmet medical need.2 years ago