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)-China Extension Study
Study Details
Study Description
Brief Summary
The purpose of this China extension study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in adult Chinese 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 |
|---|---|---|
|
Phase 3 |
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-4280A-007 (NCT05064059) plus those enrolled during the China extension enrollment period. A total of approximately 94 Chinese participants will be enrolled.
Study Design
Arms and Interventions
| 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 Names:
|
| 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:
Drug: TAS-102
Oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Up to approximately 26 months]
OS is defined as the time from randomization to death due to any cause.
Secondary Outcome Measures
- 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) [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.
- Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [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.
- Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [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.
- Number of Participants Who Experience at least One Adverse Event (AE) [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.
- Number of Participants Who Discontinue Study Treatment Due to an AE [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.
- 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 [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.
- Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score [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.
- Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score [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.
- Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score [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.
- Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score [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.
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score [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.
- TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score [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.
- TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable.
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Has measurable disease per RECIST 1.1 as assessed by the local site investigator.
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Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment.
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Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated.
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Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.
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Has a life expectancy of at least 3 months, based on the investigator assessment.
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Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
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Has adequate organ function.
Exclusion Criteria:
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Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status.
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease.
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Has a history of acute or chronic pancreatitis.
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Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
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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.
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Has urine protein greater than or equal to 1g/24h.
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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.
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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).
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Has previously received regorafenib or TAS-102.
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Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization.
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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.
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Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
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Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
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Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
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Has an active autoimmune disease that has required systemic treatment in past 2 years.
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Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
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Has an active infection requiring systemic therapy (eg, tuberculosis, known viral or bacterial infections, etc.).
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Has a known history of human immunodeficiency virus (HIV) infection.
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Has known history of Hepatitis B or known active Hepatitis C virus infection.
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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.
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Has had an allogenic tissue/solid organ transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Second Affiliated Hospital of Anhui Medical University ( Site 1179) | Hefei | Anhui | China | 230601 |
| 2 | Chongqing Cancer Hospital ( Site 1151) | Chongqing | Chongqing | China | 400030 |
| 3 | Fujian Province Cancer Hospital ( Site 1178) | Fuzhou | Fujian | China | 350014 |
| 4 | Sun Yat-Sen University Cancer Center ( Site 1150) | Guangzhou | Guangdong | China | 510060 |
| 5 | Southern Medical University Nanfang Hospital ( Site 1154) | Guangzhou | Guangdong | China | 510515 |
| 6 | The Sixth Affiliated Hospital of Sun Yat-sen University ( Site 1159) | Guangzhou | Guangdong | China | 510655 |
| 7 | Guangxi Medical University Affiliated Tumor Hospital ( Site 1158) | Nanning | Guangxi | China | 531021 |
| 8 | Hainan General Hospital ( Site 1177) | Haikou | Hainan | China | 570311 |
| 9 | Wuhan Union Hospital Cancer Center ( Site 1162) | Wuhan | Hubei | China | 430022 |
| 10 | Hubei Cancer Hospital ( Site 1152) | Wuhan | Hubei | China | 430079 |
| 11 | Xiangya Hospital Central South University ( Site 1171) | Changsha | Hunan | China | 410008 |
| 12 | Hunan Cancer Hospital ( Site 1174) | Changsha | Hunan | China | 410013 |
| 13 | The Third Xiangya Hospital of Central South University ( Site 1175) | Changsha | Hunan | China | 410013 |
| 14 | Changzhou Cancer Hospital-Department of Oncology ( Site 1183) | Changzhou | Jiangsu | China | 213000 |
| 15 | Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) ( Site 1185) | Wuxi City | Jiangsu | China | 214122 |
| 16 | Jilin Cancer Hospital ( Site 1163) | Changchun | Jilin | China | 130012 |
| 17 | Jinan Central Hospital ( Site 1167) | Jinan | Shandong | China | 250000 |
| 18 | Fudan University Shanghai Cancer Center ( Site 1176) | Shangai | Shanghai | China | 201321 |
| 19 | Shanghai Tenth People's Hospital ( Site 1170) | Shanghai | Shanghai | China | 200072 |
| 20 | West China Hospital Sichuan University ( Site 1172) | Chengdu | Sichuan | China | 332001 |
| 21 | Tianjin Medical University Cancer Institute and Hospital ( Site 1161) | Tianjin | Tianjin | China | 300060 |
| 22 | Yunnan Province Cancer Hospital-Colorectal surgery ( Site 1169) | Kunming | Yunnan | China | 650106 |
| 23 | Zhejiang Cancer Hospital ( Site 1180) | Hangzhou | Zhejiang | China | 310005 |
| 24 | Sir Run Run Shaw Hospital-Medical Oncology ( Site 1173) | Hangzhou | Zhejiang | China | 310018 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 4280A-007 China Extension
- MK-4280A-007 China Extension
- jRCT2031210482