Phase A Phase 2 Study Evaluating Response and Biomarkers in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer Treated With Nivolumab in Combination With Relatlimab
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with metastatic or locally advanced microsatellite stable (MSS) colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •ECOG performance status 0 or 1
- •Have metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma.
- •Cohort A: Primary lesion has a composite PD-L1/Mucin (CPM) score ≥ 15%.
- •Cohort B: Primary lesion has a composite PD-L1/Mucin (CPM) score < 15%.
- •Cohort C: Prior surgical resection of primary tumor. Prospective biomarker evaluation not required.
- •Must have received at least one chemotherapy regimen.
- •Patients with the presence of at least one measurable lesion using RECIST 1.
- •Patients must have available archival tissue from the surgical resection of their primary tumor.
- •Patient's acceptance of tumor biopsies.
- •Life expectancy of greater than 3 months.
- •Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
- •Documented LVEF ≥ 50% - 6 month prior to drug administration.
- •Must use acceptable form of birth control while on study.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Known history or evidence of brain metastases. Patients with previously treated brain metastases may participate if they are stable for 4 weeks prior to beginning treatment, have no new or enlarging brain metastases, and are not using steroids for at least 1 week prior to initiation of study treatment.
- •Require any antineoplastic therapy.
- •History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or anti-Lag-3 antibodies.
- •Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
- •Had any cytotoxic drug within 4 weeks prior to initiation of study treatment.
- •Hypersensitivity reaction to any monoclonal antibody.
- •Has uncontrolled intercurrent acute or chronic medical illness.
- •Has an active known or suspected autoimmune disease.
- •Has a diagnosis of immunodeficiency.
- •Prior tissue or organ allograft or allogeneic bone marrow transplantation.
- •Requires daily supplemental oxygen
- •History of interstitial lung disease.
- •Requires daily supplemental oxygen.
- •Significant heart disease
- •History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
- •Infection with HIV or hepatitis B or C at screening.
- •Has an active infection.
- •Unable to have blood drawn.
- •Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Woman who are pregnant or breastfeeding.
研究组 & 干预措施
Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of greater than or equal to 15% was used to determine CPM positivity.
Participants received 480mg Nivolumab and 160mg Relatlimab.
干预措施: Nivolumab (Drug)
Cohort A: Composite PD-L1/Mucin (CPM) positive colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of greater than or equal to 15% was used to determine CPM positivity.
Participants received 480mg Nivolumab and 160mg Relatlimab.
干预措施: Relatlimab (Drug)
Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of less than 15% was used to determine CPM negativity.
Participants received 480mg Nivolumab and 160mg Relatlimab.
干预措施: Nivolumab (Drug)
Cohort B: Composite PD-L1/Mucin (CPM) negative colorectal cancer
Participants were pre-screened for CPM score. The CPM score integrates the percent of PD-L1 expression at the tumor interface and the percent of acellular mucin in the tumor area ([%PD-L1 + % acellular mucin]/2) using each participant's primary tumor tissue. A CPM score cutoff of less than 15% was used to determine CPM negativity.
Participants received 480mg Nivolumab and 160mg Relatlimab.
干预措施: Relatlimab (Drug)
Cohort C: Colorectal cancer with no biomarker evaluation required
Participants were not pre-screened for composite PD-L1/mucin (CPM) score.
Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg).
干预措施: Nivolumab (Drug)
Cohort C: Colorectal cancer with no biomarker evaluation required
Participants were not pre-screened for composite PD-L1/mucin (CPM) score.
Participants received 480mg Nivolumab and 960mg Relatlimab (dose reduced to 480mg or 160mg).
干预措施: Relatlimab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 12 months
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.
次要结局
- Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation(12 months)