Colorectal Cancer
Conditions
Keywords
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)
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.
Interventions
BIOLOGICALfavezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion
DRUGregorafenib
Oral
DRUGTAS-102
Oral
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open-label)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 33 months | OS was defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR | Up to approximately 21 months | 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. |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR | Up to approximately 21 months | 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. |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to approximately 31 months | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 28 months | 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. |
| 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 8 weeks | 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. |
| Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score | Baseline and up to approximately 8 weeks | 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 |
| 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) | Up to approximately 21 months | 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. |
| 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 8 weeks | 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 38 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). 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. |
| TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score | Baseline and up to approximately 38 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). 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. |
| TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score | Baseline and up to approximately 38 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 38 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. |
| Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score | Baseline and up to approximately 8 weeks | 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. |
Countries
Australia, Canada, Chile, China, Czechia, France, Germany, Israel, Italy, Japan, Malaysia, Norway, Russia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Favezelimab/Pembrolizumab Participants received coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions. | 221 |
| Standard of Care (Regorafenib or TAS-102) At the Investigator's choice, participants received 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle OR 35 mg/m\^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle. | 220 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 199 | 196 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Sponsor Decision | 14 | 11 |
| Overall Study | Withdrawal by Subject | 4 | 11 |
Baseline characteristics
| Characteristic | Favezelimab/Pembrolizumab | Standard of Care (Regorafenib or TAS-102) | Total |
|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 11.3 | 57.6 Years STANDARD_DEVIATION 11.4 | 58.8 Years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 17 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 197 Participants | 196 Participants | 393 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 12 Participants |
| Geographic Region Asia Pacific | 71 Participants | 70 Participants | 141 Participants |
| Geographic Region EMEA/Americas | 150 Participants | 150 Participants | 300 Participants |
| Presence of Liver Metastasis No | 49 Participants | 47 Participants | 96 Participants |
| Presence of Liver Metastasis Yes | 172 Participants | 173 Participants | 345 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 67 Participants | 65 Participants | 132 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 145 Participants | 147 Participants | 292 Participants |
| Sex: Female, Male Female | 83 Participants | 81 Participants | 164 Participants |
| Sex: Female, Male Male | 138 Participants | 139 Participants | 277 Participants |
| Time from Initial Diagnosis of Metastatic Disease to Randomization <18 months | 77 Participants | 70 Participants | 147 Participants |
| Time from Initial Diagnosis of Metastatic Disease to Randomization ≥18 months | 144 Participants | 150 Participants | 294 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 202 / 221 | 203 / 220 |
| other Total, other adverse events | 193 / 221 | 187 / 210 |
| serious Total, serious adverse events | 75 / 221 | 56 / 210 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 33 months
Population: All randomized participants were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Overall Survival (OS) | 7.3 Months |
| Standard of Care (Regorafenib or TAS-102) | Overall Survival (OS) | 8.5 Months |
p-value: 0.418395% CI: [0.8, 1.2]Log Rank
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had at least one EORTC QLQ-C30 assessment data available for this outcome measure were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score | 8.04 Score on a scale |
| Standard of Care (Regorafenib or TAS-102) | Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score | 4.18 Score on a scale |
p-value: 0.184695% CI: [-1.85, 9.57]t-test, 2 sided
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had at least one EORTC QLQ-C30 assessment data available for this outcome measure were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score | -7.13 Scores on a scale |
| Standard of Care (Regorafenib or TAS-102) | Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score | -6.17 Scores on a scale |
p-value: 0.63795% CI: [-4.93, 3.02]t-test, 2 sided
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had at least one EORTC QLQ-CR29 assessment data available for this outcome measure were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score | 4.33 Score on a scale |
| Standard of Care (Regorafenib or TAS-102) | Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score | 3.77 Score on a scale |
p-value: 0.84195% CI: [-4.96, 6.08]t-test, 2 sided
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had at least one EORTC QLQ-C30 assessment data available for this outcome measure were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | 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 | -7.11 Score on a scale |
| Standard of Care (Regorafenib or TAS-102) | 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 | -4.03 Score on a scale |
p-value: 0.131895% CI: [-7.09, 0.93]t-test, 2 sided
Secondary
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
Population: All randomized participants who experienced a confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR | NA Months |
| Standard of Care (Regorafenib or TAS-102) | Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR | NA Months |
Secondary
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
Population: All randomized participants who received at least one dose of study intervention were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Favezelimab/Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an AE | 21 Participants |
| Standard of Care (Regorafenib or TAS-102) | Number of Participants Who Discontinued Study Treatment Due to an AE | 19 Participants |
Secondary
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
Population: All randomized participants who received at least one dose of study intervention were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Favezelimab/Pembrolizumab | Number of Participants Who Experienced at Least One Adverse Event (AE) | 205 Participants |
| Standard of Care (Regorafenib or TAS-102) | Number of Participants Who Experienced at Least One Adverse Event (AE) | 199 Participants |
Secondary
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
Population: All randomized participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Favezelimab/Pembrolizumab | Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR | 6.8 Percentage of Participants |
| Standard of Care (Regorafenib or TAS-102) | Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR | 0.9 Percentage of Participants |
p-value: 0.000795% CI: [2.5, 10.1]Miettinen & Nurminen Method
Secondary
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
Population: All randomized participants were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | 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) | 2.1 Months |
| Standard of Care (Regorafenib or TAS-102) | 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) | 2.6 Months |
p-value: 0.996795% CI: [1.09, 1.64]Log Rank
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had EORTC QLQ-C30 assessment data available at baseline for this outcome measure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score | NA Months |
| Standard of Care (Regorafenib or TAS-102) | Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score | NA Months |
p-value: 0.509495% CI: [0.64, 1.58]Log Rank
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had EORTC QLQ-C30 assessment data available at baseline for this outcome measure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score | NA Months |
| Standard of Care (Regorafenib or TAS-102) | TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score | 20.3 Months |
p-value: 0.970495% CI: [0.98, 2.33]Log Rank
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had EORTC QLQ-CR29 assessment data available at baseline for this outcome measure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score | NA Months |
| Standard of Care (Regorafenib or TAS-102) | TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score | NA Months |
p-value: 0.985395% CI: [1.06, 3.26]Log Rank
Secondary
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
Population: All randomized participants who have received at least one dose of the study intervention and had EORTC QLQ-C30 assessment data available at baseline for this outcome measure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favezelimab/Pembrolizumab | TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score | NA Months |
| Standard of Care (Regorafenib or TAS-102) | TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score | NA Months |
p-value: 0.990595% CI: [1.11, 2.98]Log Rank