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LBA9513 Background: Adjuvant immune checkpoint blockade (ICB) and target therapy (TT) improve outcomes of patients (pts) with high-risk resectable melanoma. Prospective neoadjuvant (NAT) clinical trials with TT or ICB are now running in a subgroup of high-risk melanoma pts with pooled overall promising preliminary results of high rates of pathologic complete responses (pCRs, 30–50%) and early data of positive correlation between pCR and relapse-free survival (RFS). We aimed to conduct a randomized, non-comparative phase II trial to define the role of NAT plus adjuvant TT and ICB, given in combination or sequence, in pts with high risk surgically resectable melanoma. Methods: 95 pts with resectable, RECIST measurable stage IIIB/IV, BRAF-mutant melanoma were randomized 1:1 in arm A and arm B, respectively, to receive NAT vemurafenib (V) and cobimetinib (C) for 6 weeks or NAT triplet combination (V and C plus atezolizumab (A), followed by complete lymph node dissection (CLND). Patients with BRAF wild-type melanoma were included in Arm C with NAT C and A. All pts had 17 cycles of A 1200 mg IV q3w post-CLND. Primary endpoint is pCR centrally/independently determined defined as residual cancer burden 0. Secondary endpoints are RFS, Overall Survival (OS), Pathological Overall Response Rate (pORR), Safety, Biomarkers analyses. Results: At data cut-off Dec 15, 2023, 29% of pts were female, median age was 59 yrs, 60% had a clinical stage IIIC, and median f/u was 17 months (IQR: 10-22). The Major Pathological Response (defined as pCR/near-pCR) was reached in 13 (45%), 10 (34%) and 13 (36%) pts in arm A, B and C, respectively. Five (17%), 4 (14%) and 6 (16%) pts did not receive surgery, and 1 (3%) patient of arm B is still under evaluation of pathological respose rate (pRR). At 12 months,RFS was 78%, 86% and 82% in arm A, B and C, respectively. Nearly 19% of pts treated in arm C were discontinued before surgery due to PD, AEs or patient’s withdrawn consent, 7% and 14% in arm B and A, respectively, due to comorbidities and AEs. G3-G4 toxicity was observed in 38%, 24% and 22% of pts in arm A, B and C. Conclusions: Pts treated with TT upfront had highest response to NAT but the pts who received IO as NAT had a better RFS. Clinical trial information: NCT04722575 . Table: see text
Ascierto et al. (Wed,) studied this question.