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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)

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ClinicalTrials.gov Identifier: NCT05064059
Recruitment Status : Recruiting
First Posted : October 1, 2021
Last Update Posted : June 27, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: favezelimab/pembrolizumab Drug: regorafenib Drug: TAS-102 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 432 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: None (Open-label)
Primary Purpose: Treatment
Official Title: A Phase 3 Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Standard of Care in Previously Treated Metastatic PD-L1 Positive Colorectal Cancer
Actual Study Start Date : November 10, 2021
Estimated Primary Completion Date : February 9, 2024
Estimated Study Completion Date : November 11, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Favezelimab/Pembrolizumab
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions.
Biological: favezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion
Other Name: MK-4280A

Active Comparator: Standard of Care (Regorafenib or TAS-102)
Participants will receive 160 mg regorafenib orally daily on Days 1-21 of each 28-day cycle. Participants will also receive 35 mg/m^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day treatment cycle.
Drug: regorafenib
Oral
Other Names:
  • STIVARGA®
  • REGONIX®

Drug: TAS-102
Oral
Other Name: LONSURF®




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 26 months ]
    OS is defined as the time from randomization to death due to any cause.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) according per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 19 months ]
    PFS is 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 occurs first.

  2. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 19 months ]
    The ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.

  3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 19 months ]
    For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

  4. Number of Participants Who Experience at least One Adverse Event (AE) [ Time Frame: Up to approximately 27 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.

  5. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 24 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. The number of participants who discontinue study treatment due to an AE will be reported.

  6. 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 [ Time Frame: Baseline and up to approximately 25 months ]
    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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome.

  7. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score [ Time Frame: Baseline and up to approximately 25 months ]
    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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function.

  8. Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score [ Time Frame: Baseline and up to approximately 25 months ]
    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.

  9. Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score [ Time Frame: Baseline and up to approximately 25 months ]
    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.

  10. Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score [ Time Frame: Baseline and up to approximately 25 months ]
    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). 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 GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.

  11. TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score [ Time Frame: Baseline and up to approximately 25 months ]
    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). 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 GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.

  12. TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score [ Time Frame: Baseline and up to approximately 25 months ]
    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.

  13. TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score [ Time Frame: Baseline and up to approximately 25 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05064059


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 129 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05064059    
Other Study ID Numbers: 4280A-007
MK-4280A-007 ( Other Identifier: Merck )
jRCT2031210482 ( Registry Identifier: jRCT(Japan Registry of Clinical Trials) )
2021-001309-60 ( EudraCT Number )
First Posted: October 1, 2021    Key Record Dates
Last Update Posted: June 27, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme LLC:
Programmed Cell Death-1 (PD1, PD-1),
Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1)
Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents