Adjuvant immunotherapy with anti-PD-1 monoclonal antibody Pembrolizumab (MK-3475) versus placebo after complete resection of high-risk Stage III melanoma: A randomized, double- blind Phase 3 trial of the EORTC Melanoma Group

Phase 1

Recruiting

• Conditions: Stage III melanoma (AJCC R0) with histologically confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC, 2010): Stage IIIA with metastasis > 1 mm; any Stage IIIB or IIIC (no in-transit metastases); MedDRA version: 21.1Level: PTClassification code: 10025670Term: Malignant melanoma stage III Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-509136-25-00
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-31
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 1019

Inclusion Criteria

Patient enrollment will follow a three steps procedure as illustrated in Section 4 (step 1 registration, step 2 central confirmation of PD-L1 expression, step 3 enrollment and randomization through IVRS). Patients must meet all of the criteria described in Section 3 to be eligible for enrollment. 1) Registration- step 1 (ORTA Step 1) Before patient registration, written informed consent for tumor testing must be given according to ICH/GCP, and national/local regulations. Note: if a patient signs the Registration Informed Consent before the complete lymph node dissection (CLND) was performed, please contact the medical monitor to assess eligibility before registering in ORTA. ? At least 18 years of age. ? No mucosal or ocular melanoma. ? Melanoma with unknown origin of the primary is eligible. ? Complete resection of Stage III melanoma (AJCC R0) with histologically confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC, 2010): Stage IIIA with metastasis > 1 mm; any Stage IIIB or IIIC. No past or current in-transit metastases or satellitosis. ? Patient population IIIA (> 1 mm metastasis) is capped at a maximum of 20% of the total patient population. ? Mandatory to ship tumor sample for evaluation of PD-L1 expression. A tumor sample obtained at resection or tissue obtained from the biopsy must not be previously irradiated. During the screening period, the tumor sample must be sent to the central pathology laboratory for PD-L1 expression testing. Patients will be eligible to participate regardless of the level of PD-L1 expression. ? PD-L1 testing is mandatory: tumor material will be collected from positive lymph nodes (LN) embedded in paraffin. If the resection samples from LNs are not adequate for PD-L1 testing, the primary melanoma must be collected. Patients whose samples are inadequate for PD-L1 determination will not be enrolled. ? In addition the primary melanoma may also be collected if available to evaluate the PD-L1 expression., 2) Central confirmation of PD-L1 expression - step 2 This central confirmation through EORTC is required for enrolling the patient in step 3., 3) Enrollment and randomization -step 3 (ORTA Step 2) Before patient enrollment, written informed consent to participate in the trial must be given according to ICH/GCP, and national/local regulations. ? The resection of Stage III lymph nodes must have been performed in complete compliance with the Criteria for adequate surgical procedures for CLND that is displayed in Appendix F. This must be documented in the medical file (including pathology report); patients without documentation of adequate resection are not eligible. ? To be considered as adequate, the surgical and pathological procedures should have included at least the following: ? Head and Neck ? Minimum of 15 pathologically investigated nodes ? Face, ear, and anterior scalp: parotidectomy plus modified radical neck dissection ? Posterior scalp: modified radical neck dissection plus suboccipital nodes. For this specific localization, a CLND will be considered as adequate if at least 5 LN have been investigated ? Upper Extremity ? Minimum of 10 pathologically investigated nodes ? Axillary node dissection included at least 10 nodes taken from Levels I and II ? Level III nodes dissected if they were clinically involved ? Pectoralis minor muscle may be divided or sacrificed with the specimen at the discretion of the surgeon ? Lower Extremity ? Minimum of 5 pathologically investigated nodes

Exclusion Criteria

Not available. According to study design, all exclusion criteria are included within inclusion criteria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified