A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084, Cetuximab, and mFOLFOX6 Versus mFOLFOX6 With or Without Bevacizumab as First-line Treatment of Participants With KRAS G12C-mutant, Locally Advanced Unresectable or Metastatic Colorectal Cancer (KANDLELIT-012)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 477
- 试验地点
- 307
- 主要终点
- Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
研究概览
简要总结
Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C.
Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies.
The goals of this study are to learn:
- About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments
- If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.
详细描述
This study will have 2 parts.
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
- Single (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 criteria include but are not limited to the following:
- •Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer [AJCC] eighth edition) colorectal adenocarcinoma
- •Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
- •Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
- •Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
- •Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
- •Has active infection requiring systemic therapy
- •Has not adequately recovered from major surgery or have ongoing surgical complications
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
研究组 & 干预措施
mFOLFOX6
Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.
干预措施: Leucovorin/levofolinate calcium (Drug)
mFOLFOX6
Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.
干预措施: Bevacizumab (Drug)
mFOLFOX6
Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.
干预措施: Oxaliplatin (Drug)
mFOLFOX6
Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.
干预措施: 5-Fluorouracil (Drug)
Calderasib + Cetuximab + mFOLFOX6
Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.
干预措施: Calderasib (Drug)
mFOLFOX6
Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.
干预措施: Bevacizumab biosimilar (Drug)
Calderasib + Cetuximab + mFOLFOX6
Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.
干预措施: Leucovorin/levofolinate calcium (Drug)
Calderasib + Cetuximab + mFOLFOX6
Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.
干预措施: 5-Fluorouracil (Drug)
Calderasib + Cetuximab + mFOLFOX6
Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.
干预措施: Cetuximab (Biological)
Calderasib + Cetuximab + mFOLFOX6
Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
时间窗: Up to approximately 28 days
A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration.
Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
时间窗: Up to approximately 28 days
A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration.
Part 1: Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 44 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 44 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Progression Free Survival (PFS)
时间窗: Up to approximately 44 months
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
次要结局
- Objective Response Rate (ORR)(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 4 years)
- Objective Response Rate (ORR)(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 4 years)
- Part 2: Number of Participants with an Adverse Event (AE)(Up to approximately 5 years)
- Part 2: Number of Participants who Discontinue Study Treatment Due to an AE(Up to approximately 5 years)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 5 years)
- Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 5 years)
- Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score(Baseline and up to approximately 5 years)
- Change from Baseline in the EORTC-QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 5 years)
- Change from Baseline in the EORTC-Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score(Baseline and up to approximately 5 years)
- Time to First Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 5 years)
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score(Baseline and up to approximately 5 years)
- TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score(Baseline and up to approximately 5 years)
- TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score(Baseline and up to approximately 5 years)
- TTD in EORTC QLQ-CR29 Bloating (Item 37) Score(Baseline and up to approximately 5 years)