Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: A randomized open-label phase II study of the EORTC Melanoma Group (16032- 18031)

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9065 Background: The MAGE-A3 antigen, expressed in ±60% of metastatic melanomas, is a target of anti-tumor CD4+ and CD8+ T-cells. Previous data showed a few clinical responses of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic in melanoma. This study was designed to evaluate MAGE-A3 recombinant protein combined with different Adjuvant Systems (AS). Methods: Patients (pts) with measurable metastatic MAGE-A3 (+) cutaneous melanoma (unresectable or in transit stage III or stage IV M1a) were randomized between immunization with MAGE-A3 protein combined with AS15 (CpG/MPL/QS21) or with AS02B (MPL/QS 21) as 1st line metastatic treatment. Pts received immunizations every 2 weeks for 6 doses. Those with clinical benefit received additional maintenance treatment for up to 4 yrs. Primary endpoints were CTC grade III/IV toxicity, objective response rate; secondary endpoints were immune response, progression- free survival. Planned sample size was 68 pts. Results: 91 out of 165 screened (55%) had MAGE-A3 (+) tumor biopsies and 75 pts were randomized. Among 72 eligible pts median age: 66 y (range 29–866 y), male: 36%, ECOG = 0: 93%, stage III in-transit: 26%, unresectable stage III: 46%, stage IV M1a: 28%. Toxicity in both treatment arms was comparable, mainly grade I/II with injection site reaction and constitutional symptoms (96%), rarely grade III/IV. Median number of immunizations was 9 (range 2–22). Objective responses (CR, PR) were reported in 3 pts (11, 23+, 24+ mns), 1 pt (5 mns) (AS15) and 0, 1 pt (6 mns) (AS02B). Stable disease (SD) > 16 wk was reported in 6 vs 5 pts in the 2 arms respectively. Anti-MAGE-3 antibody titers were higher in AS15 arm than in AS02B arm. CD4+ T-cell responses were observed in 72% (AS15) versus 36% (AS02B). Conclusions: The combination of MAGE-A3 + AS15 yielded higher specific Ab titers, more robust T-cell induction and long-lasting clinical responses or SD in metastatic melanoma. This warrants further development. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline