Melanoma
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT)
Brief summary
The primary purpose of this study is to compare pembrolizumab/vibostolimab to pembrolizumab with respect to recurrence-free survival (RFS). The primary hypothesis is that pembrolizumab/vibostolimab is superior to pembrolizumab with respect to RFS as assessed by the investigator in participants with high-risk resected Stage IIB, IIC, III and IV melanoma.
Detailed description
With Amendment 4, participants will discontinue treatment with pembrolizumab/vibostolimab. The protocol-specified futility analysis of the primary outcome measure was completed with a data cut-off of 06-Mar-2024 (Primary Completion Date) and served as the final analysis of the primary outcome measure. Per protocol, 192 participants enrolled after the primary completion date and will be analyzed in the End of Trial analysis.
Interventions
BIOLOGICALPembrolizumab/Vibostolimab
Co-formulation of pembrolizumab 200 mg/20 mL vial and vibostolimab 200 mg administered as IV infusion for up to 17 administrations
BIOLOGICALPembrolizumab
Pembrolizumab 25 mg/mL administered as IV infusion for up to 17 administrations
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has surgically resected and histologically or pathologically confirmed diagnosis of Stage IIB and IIC (pathological or clinical), III, or IV cutaneous melanoma per the American Joint Committee on Cancer (AJCC) eighth edition guidelines * Has not received any prior systemic therapy for melanoma beyond surgical resection * Has had no more than 12 weeks between final surgical resection and randomization * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART) * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Exclusion criteria
* Has ocular, mucosal, or conjunctival melanoma * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * Has not adequately recovered from major surgical procedure or has ongoing surgical complications * Has received prior radiotherapy within 2 weeks of start of study intervention or has had a history of radiation pneumonitis * Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has an active autoimmune disease that has required systemic treatment in past 2 years * Has an active infection requiring systemic therapy * Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival (RFS) | Up to approximately 13 months | RFS is defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) as assessed by the investigator, or death due to any cause, whichever occurs first. The RFS as assessed by the investigator is presented for all randomized participants. Protocol pre-specified final analysis for this outcome measure was conducted with the primary completion data cut-off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to approximately 31 months | An adverse event (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 experienced an AE is presented. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 31 months | An adverse event (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 study treatment due to an AE is presented. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, France, Germany, India, Ireland, Israel, Italy, Japan, New Zealand, Poland, South Africa, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Protocol-specified final analysis for the following results, including the participant flow, was performed on 1402 participants that enrolled within the primary completion data cut-off. Analysis of the remaining 192 enrolled participants will be included in the End of Trial analysis.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab/Vibostolimab Participants received pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to \
1 year). | 701 |
| Pembrolizumab Participants received 200 mg pembrolizumab via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to \
1 year). | 701 |
| Total | 1,402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Ongoing | 692 | 698 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Pembrolizumab | Total | Pembrolizumab/Vibostolimab |
|---|---|---|---|
| Age, Continuous | 59.2 Years STANDARD_DEVIATION 13.9 | 59.1 Years STANDARD_DEVIATION 13.9 | 59.0 Years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 73 Participants | 157 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 586 Participants | 1171 Participants | 585 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 42 Participants | 74 Participants | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 139 Participants | 273 Participants | 134 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 554 Participants | 1107 Participants | 553 Participants |
| Region of Enrollment Asia | 135 Participants | 268 Participants | 133 Participants |
| Region of Enrollment Rest of the World (ROW) | 566 Participants | 1134 Participants | 568 Participants |
| Risk-based Melanoma Stage Stage IIB/IIC/clinical IIB and IIC/IIIA/IIIB | 427 Participants | 854 Participants | 427 Participants |
| Risk-based Melanoma Stage Stage IIIC/IIID/IV | 274 Participants | 548 Participants | 274 Participants |
| Sex: Female, Male Female | 291 Participants | 573 Participants | 282 Participants |
| Sex: Female, Male Male | 410 Participants | 829 Participants | 419 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 701 | 1 / 701 |
| other Total, other adverse events | 462 / 698 | 426 / 700 |
| serious Total, serious adverse events | 109 / 698 | 57 / 700 |
Outcome results
Primary
Recurrence-Free Survival (RFS)
RFS is defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) as assessed by the investigator, or death due to any cause, whichever occurs first. The RFS as assessed by the investigator is presented for all randomized participants. Protocol pre-specified final analysis for this outcome measure was conducted with the primary completion data cut-off.
Time frame: Up to approximately 13 months
Population: Per protocol, analysis population consisted of all participants randomized, by the primary completion data cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab/Vibostolimab | Recurrence-Free Survival (RFS) | NA Months |
| Pembrolizumab | Recurrence-Free Survival (RFS) | NA Months |
95% CI: [0.87, 1.8]
Secondary
Number of Participants Who Discontinued Study Treatment Due to an AE
An adverse event (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 study treatment due to an AE is presented.
Time frame: Up to approximately 31 months
Secondary
Number of Participants Who Experienced at Least One Adverse Event (AE)
An adverse event (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 experienced an AE is presented.
Time frame: Up to approximately 31 months