Phase 3 Study of Adjuvant V940 and Pembrolizumab in Resected Melanoma
A Phase 3, Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Clinical study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants with High-Risk Stage II-IV Melanoma
Clinical Trial Information
Trial Contact: Frankos, Marie; Caldwell, Chloe M; Donaldson, Karin M
To compare V940 plus pembrolizumab to placebo plus pembrolizumab with respect to RFS.
Hypothesis (H1): V940 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to RFS as assessed by the investigator.
An individual is eligible for inclusion in the study if the individual meets all of the following criteria:
Type of Participant and Disease Characteristics
1. Has surgically resected and histologically/pathologically confirmed diagnosis of Stage IIB or IIC (pathological or clinical), III, or IV cutaneous melanoma (including acral) per AJCC eighth edition guidelines (Appendix 9). Participants with BRAF-mutated melanoma are eligible.
• Note: A therapeutic lymph node dissection defined as an anatomically complete lymphadenectomy of the involved nodal basin for macroscopic disease (clinically, radiographically, or sonographically [if performed] detectable lymph nodes) is required [Appendix 8]. SLN biopsy and CLND for microscopic lymph node disease are not required.
• Note: Participants with recurrent disease who had prior resection are allowed as long as all current disease has been resected and archival tissue (from most recent recurrence) is available for NGS.
• Note: Melanoma of unknown primary is eligible. Enrollment of participants with acral melanoma will be capped at 10% of the total population.
2. Has not received any prior systemic therapy for their melanoma beyond surgical resection.
• Note: Radiotherapy of the either primary lesion or after lymph node dissection is permitted but must be completed by 11 weeks after surgery and 2 weeks before the first dose of pembrolizumab.
• Note: Radiotherapy may alter the process of wound healing. If the wound healing is not complete, the participant is not eligible.
3. No more than 13 weeks have elapsed between final surgical resection and the first dose of pembrolizumab. Treatment should start only after adequate wound healing from the surgical procedure as assessed by the investigator. If there is a delay of ≤2 weeks exceeding 13 weeks due to unforeseen circumstances, the eligibility should be discussed with the Sponsor and the decision documented. Participants must have recovered from surgery and any post-operative complications before the first dose of pembrolizumab.
• Note: Final surgical resection is defined in this protocol as the final surgical procedure required to achieve complete resection of melanoma and render the participant disease free.
4. Has an FFPE tumor sample available (from their recent surgery) that is suitable for the NGS required for this study. The tumor sample must meet the following criteria:
• Meet the minimum standards for tissue quantity and quality as defined in the Procedures/Laboratory manual for this study.
• Pass the required QC checks for NGS by the Sponsor’s NGS vendor.
5. Is disease free at the time of providing documented consent for the main study (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases. Disease free status must be confirmed within 28 days of starting study intervention by full chest/abdomen/pelvis CT or MRI and neck CT or MRI (only for participants with primary tumors of the head and neck) and complete clinical examination. Head CT with and without contrast is acceptable for any participant for whom brain MRI is contraindicated.
6. All suspicious lesions amenable to biopsy should be confirmed negative for malignancy.
7. Has an ECOG performance status of 0 or 1 within 7 days of the first dose of pembrolizumab.
8. Is an individual of any sex/gender, from 18 years of age at the time of providing the full informed consent.
No contraception measures are required for participants capable of producing sperm.
• A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a POCBP
• Is a POCBP and:
• Uses a contraceptive method that is highly effective (with a failure rate of <1% per year) or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
• Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. The participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5.
• Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention with V940 / placebo or pembrolizumab.
• Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
9. The participant (or legally acceptable representative) has provided documented informed consent (full consent) for the study.
10. Adequate organ function as defined in the following table (Table 3). Specimens must be collected within 7 days before the start of study intervention.
11. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
• Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority
12. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization.
Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local health authority
14. HIV-infected participants must have well controlled HIV on ART, defined as:
a) Having a CD4+ T-cell count ≥350 cells/mm3 at the time of screening.
b) Having achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.
c) Have not had any AIDS-defining opportunistic infections within the past 12 months.
d) Have been on a stable ART regimen, without changes in drugs or dose modification, for at least 4 weeks before randomization and agree to continue ART throughout the study.