Melanoma
Conditions
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), Coxsackievirus A21, Intracellular Adhesion Molecule-1 (ICAM-1), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)
Brief summary
Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.
Interventions
BIOLOGICALPembrolizumab
Administered via IV infusion at a specified dose on specified days
BIOLOGICALVibostolimab
Administered via IV infusion at a specified dose on specified days
BIOLOGICALGebasaxturev
Administered via IT injection at a specified dose on specified days
BIOLOGICALMK-4830
Administered via IV infusion at a specified dose on specified days
BIOLOGICALFavezelimab + Pembrolizumab
Administered via IV infusion at a specified dose on specified days
DRUGATRA
Administered via oral capsules at a specified dose on specified days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytologically confirmed melanoma * Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery * Has been untreated for Stage IIIB, IIIC or IIID melanoma * Surgical resection and re-resection of primary melanoma is allowed * Prior radiotherapy to the primary melanoma is allowed * Has provided a baseline tumor biopsy * Male participants who receive gebasaxturev are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of gebasaxturev * Male participants who receive all-trans retinoic acid (ATRA) are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of ATRA * Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, vibostolimab, gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last dose of ATRA, whichever occurs last * Has adequate organ function * Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
Exclusion criteria
* Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention * Has a known additional malignancy that is progressing or requires active treatment within the past 2 years * Has known central nervous system (CNS) metastases and/or carcinomatous meningitis * Has ocular or mucosal melanoma * Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody (mAb) * Has an active autoimmune disease that has required systemic treatment in the past 2 years * Has an active infection requiring systemic therapy * Has known history of human immunodeficiency virus (HIV) * Has known history of hepatitis B * Has a history of (noninfectious) pneumonitis * Has a history of active tuberculosis (TB) * Has received prior systemic anticancer therapy within 4 weeks prior to randomization * Has received prior radiotherapy within 2 weeks of first dose of study intervention * Has had major surgery \<3 weeks prior to first dose of study intervention * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention * Has had an allogeneic tissue/solid organ transplant * Has only mucosal lesions * Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to approximately 17 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 percentage of participants who experienced an AE was reported. |
| Percentage of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 13 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 percentage of participants who discontinued study intervention due to an AE was reported. |
| Pathological Complete Response (pCR) Rate With 90% Confidence Interval (CI) | Up to approximately 6 weeks | pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 90% CI was reported. |
| pCR Rate With 95% CI | Up to approximately 6 weeks | pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 95% CI was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Near pCR Rate With 90% CI | Up to approximately 6 weeks | Near pCR was defined as the percentage of participants with \>0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 90% CI was reported. |
| Near pCR Rate With 95% CI | Up to approximately 6 weeks | Near pCR was defined as the percentage of participants with \>0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 95% CI was reported. |
| Pathological Partial Response (pPR) Rate With 90% CI | Up to approximately 6 weeks | pPR rate was defined as the percentage of participants with \>10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 90% CI was reported. |
| pPR Rate With 95% CI | Up to approximately 6 weeks | pPR rate was defined as the percentage of participants with \>10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 95% CI was reported. |
| Recurrence-Free Survival (RFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by The Investigator | Up to approximately 62 months | RFS was defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) per RECIST 1.1 as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, RFS per RECIST 1.1 as assessed by the investigator was presented. |
Countries
Australia, France, Israel, Italy, Switzerland, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 139 Participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 26 | 4 / 27 | 2 / 15 | 4 / 25 | 1 / 27 | 3 / 26 |
| other Total, other adverse events | 25 / 26 | 24 / 25 | 14 / 15 | 23 / 25 | 23 / 26 | 25 / 26 |
| serious Total, serious adverse events | 3 / 26 | 6 / 25 | 3 / 15 | 10 / 25 | 9 / 26 | 9 / 26 |
Outcome results
None listed