A Phase 2 Trial to Evaluate the Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 8
- 主要终点
- Number of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
This trial will evaluate the safety and efficacy of vicriviroc (MK-7690) at 2 dose levels in combination with pembrolizumab (MK-3475) in participants with advanced/metastatic microsatellite stable (MSS) colorectal cancer (CRC).
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
- 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
- •Have a histologically proven locally advanced unresectable or metastatic CRC.
- •Have locally confirmed MSS CRC.
- •Have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan, and have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
- •Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
- •Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study intervention.
- •Male participants must agree to use contraception and refrain from donating sperm for at least 120 days after the last dose of study intervention.
- •Female participants must be not pregnant and not breastfeeding. Further, a female participant must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention.
- •Have adequate organ function.
排除标准
- •Have a known additional malignancy that is progressing or has required active treatment within the past 2 years. 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.
- •Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Have severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study interventions.
- •Have an active autoimmune disease requiring systemic treatment in the past 2 years, except vitiligo or resolved childhood asthma/atopy.
- •Have a history of vasculitis.
- •Have an active infection requiring systemic therapy.
- •Have symptomatic ascites or pleural effusion.
- •Have interstitial lung disease requiring oral or IV glucocorticoids.
- •Have a history of pneumonitis (noninfectious) that required steroids, or has current pneumonitis.
- •Have a known history of human immunodeficiency virus (HIV) infection.
- •Have a known history of hepatitis B or known active hepatitis C virus infection.
- •Have a known history of active tuberculosis (TB; Bacillus tuberculosis).
- •Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study interventions hazardous, or make it difficult to monitor adverse events.
- •Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with study requirements.
- •Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
- •Are a WOCBP who has a positive urine pregnancy test within 72 hours before randomization or treatment allocation.
- •Have undergone major surgery and have not recovered adequately from any toxicity and/or complications from the intervention before starting study intervention.
- •Have a seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g., CNS malignancy or toxoplasmosis).
- •Have known gastrointestinal (GI) disease such as esophageal, gastric, or duodenal ulceration or inflammatory bowel disease, or history of GI surgery.
- •Are using any drug (therapeutic or recreational), or withdrawal thereof, that poses an increased risk of convulsions.
- •Have had an allogeneic tissue/solid organ transplant.
- •Have received prior therapy with vicriviroc or other CCR5 antagonist (e.g., maraviroc) or have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent.
- •Have been treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
- •Have received prior systemic anticancer therapy, including investigational agents, or has used an investigational device within 28 days before the first dose of study intervention.
- •Have received prior radiotherapy (not to target lesions) within 2 weeks of start of study intervention.
- •Are expected to require any other form of antineoplastic therapy while on study.
- •Have a diagnosis of immunodeficiency, is receiving chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or is taking any other form of immunosuppressive medication within 7 days before the first dose of the study intervention.
- •Have received a live-virus vaccine within 30 days before the first dose of the study intervention.
- •Are currently participating in or have participated in a study of an investigational agent, or have used an investigational device within 28 days before the first dose of study intervention.
研究组 & 干预措施
Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)
Participants receive vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
干预措施: Vicriviroc (Drug)
Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)
Participants receive vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
干预措施: Pembrolizumab (Biological)
Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)
Participants receive vicriviroc 250 mg tablets PO QD of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute IV infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
干预措施: Vicriviroc (Drug)
Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)
Participants receive vicriviroc 250 mg tablets PO QD of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute IV infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to ~28 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. The number of participants with at least one AE was assessed.
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
时间窗: Up to ~32 months
Objective response rate (ORR) was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator. ORR was estimated and analyzed using Clopper-Pearson interval.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: Up to Day 21 of Cycle 1 (each cycle is 21 days)
DLTs were assessed during the first cycle (21 days) \& were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia of any duration, Gr 3 thrombocytopenia associated with bleeding; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for \>72 hours); Gr 3 or 4 febrile neutropenia; inability to receive ≥75% of the planned vicriviroc dose because of drug-related tolerability; drug-related toxicity that caused a \>2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is \>3× upper limit of normal (ULN) \& an elevated total bilirubin value \>2× ULN \& an alkaline phosphatase value \<2× ULN, in which no alternative reasons were found.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to ~25 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. The number of participants who discontinued treatment due to an AE was assessed
次要结局
- PFS Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)(Up to ~32 months)
- Plasma Area Under the Concentration Time-Curve From 0 to 8 Hours (AUC 0-8hrs) of Vicriviroc(Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.)
- Maximum Observed Plasma Concentration (Cmax) of Vicriviroc(Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.)
- Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)(Up to ~32 months)
- Overall Survival (OS)(Up to ~32 months)
- Progression-Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)(Up to ~32 months)
- Trough Plasma Concentration (Ctrough) of Vicriviroc(Pre-dose, and 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1; Cycle 3 Day 21.)