A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007)

Merck Sharp & Dohme LLC441 enrolled

Overview

The purpose of this study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in participants with metastatic colorectal cancer. The study will also compare MK-4280A with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil). The primary study hypothesis is that coformulated favezelimab/pembrolizumab (MK-4280A) is superior to standard of care with respect to overall survival.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

441

Conditions

Colorectal Cancer

Interventions

favezelimab/pembrolizumabBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable. * Has measurable disease per RECIST 1.1 as assessed by the local site investigator. * Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment. * Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated. * Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention. * Has a life expectancy of at least 3 months, based on the investigator assessment. * Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption. * Has adequate organ function. Exclusion Criteria: * Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. * Has a history of acute or chronic pancreatitis. * Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. * Has urine protein greater than or equal to 1g/24h. * A woman of childbearing potential who has a positive urine/serum pregnancy test within 24/72 hours prior to the first dose of study intervention. * Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2), anti-lymphocyte activation gene 3 (LAG-3) antibody, with a tyrosine kinase inhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF) inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, cluster of differentiation \[CD\] 137). * Has previously received regorafenib or TAS-102. * Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization. * 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-CNS disease. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its 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 (eg, tuberculosis, known viral or bacterial infections, etc.). * Has a known history of human immunodeficiency virus (HIV) infection. * Has known history of Hepatitis B or known active Hepatitis C virus infection. * Has 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, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. * Has had an allogenic tissue/solid organ transplant.

Locations (152)

Georgetown University Hospital ( Site 1148)

Washington D.C., District of Columbia, United States

Sibley Memorial Hospital ( Site 1143)

Washington D.C., District of Columbia, United States

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 1118)

Marietta, Georgia, United States

Norton Cancer Institute ( Site 1139)

Louisville, Kentucky, United States

Rutgers Cancer Institute of New Jersey ( Site 1105)

New Brunswick, New Jersey, United States

Outcomes

Primary Outcomes

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 33 months

Secondary Outcomes

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.

Time frame: Up to approximately 21 months

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants who achieved a confirmed complete response (CR: Disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesion) per RECIST 1.1 as assessed by BICR.

Time frame: Up to approximately 21 months

Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions), duration of response was defined as the time from the first documented evidence of CR or PR until progressive disease (PD) or death due to any cause. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation.

Time frame: Up to approximately 21 months

Number of Participants Who Experienced at Least One Adverse Event (AE)

An AE was 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.

Time frame: Up to approximately 31 months

Number of Participants Who Discontinued Study Treatment Due to an AE

An AE was 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. The number of participants who discontinued study treatment due to an AE is presented.

Time frame: Up to approximately 28 months

Change From Baseline in European Organisation 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

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome.

Time frame: Baseline and up to approximately 8 weeks

Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome

Time frame: Baseline and up to approximately 8 weeks

Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question "Have you lacked appetite?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score will be presented.

Time frame: Baseline and up to approximately 8 weeks

Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question "Did you have a bloated feeling in your abdomen?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score will be presented.

Time frame: Baseline and up to approximately 8 weeks

Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) \& QoL combined score (EORTC QLQ-C30 Item 30). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.

Time frame: Baseline and up to approximately 38 months

TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.

Time frame: Baseline and up to approximately 38 months

TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in appetite loss score (EORTC QLQ-C30 Item 13). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome.

Time frame: Baseline and up to approximately 38 months

TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in bloating score (QLQ-CR29 Item 37). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in appetite loss score, will be presented. A longer TTD indicates a better outcome.

Time frame: Baseline and up to approximately 38 months