A phase II, multicenter, single-arm clinical trial of response-adapted definitive radiotherapy and cemiplimab-rwlc immunotherapy for locally advanced, unresectable cutaneous squamous cell carcinoma: RAMPART.

Abstract

9506 Background: Locally advanced (T3-4/N+/M0) and unresectable cutaneous squamous cell carcinoma (LAUCSCC) patients (pts) have been historically treated with definitive radiotherapy (RT) +/- chemotherapy, yielding poor outcomes (18m progression-free survival [PFS] rates of ~38%). More recently, anti-PD1 immunotherapy with cemiplimab (cemi) led to an 18m PFS rate of ~55% in locally advanced pts that were not candidates for RT or surgery. In this prospective, multicenter trial, we assessed definitive RT with neoadjuvant, concurrent, and adjuvant cemi for LAUCSCC pts. Methods: Pts with T3-4/N+/M0 LAUCSCC according to local multidisciplinary consensus, ECOG ≤2, were enrolled and treated with 2 doses of cemi (350 mg IV q3w). Those with progressive disease (PD) after 2 doses received RT (70 Gy/35 fractions). Those without PD received 2 additional doses of cemi followed by response-adapted RT (50-70 Gy/25-35 fractions) with concurrent cemi followed by adjuvant cemi for a maximum of 1y. The primary endpoint was event free survival (EFS) at 18m after cemi start. Secondary endpoints included safety, response (by RECIST v1.1, see table), quality of life, overall survival (OS) and PFS (after RT start). To test the hypothesis that the 18m EFS was 60%, compared to a historic 18m PFS rate after RT of 38% with 80% power and 5% type 1 error rate, 34 pts were planned for enrollment (accounting for 40% attrition). Results: 34 pts (median age 77y, 82% men, ECOG 0/1/2 in 41/53/6%) were enrolled with stage III (41%) and IV/M0 (59%) LAUSCC (56% recurrent, 91% head/neck) between 2022-2024. 85% completed 4 doses of neoadjuvant cemi and 94% completed RT as planned. With median follow up of 18m (range 2-36m), 18m EFS is estimated to be 86% (1 sided 95% CI lower bound of 73%) among all pts. Adverse events were consistent with prior studies of cemi or RT. 18m PFS and OS are estimated to be 86% and 92%. Quality of life analyses are in progress. Conclusions: The study met its primary endpoint demonstrating the highest rate of EFS, PFS and OS after treatment of LAUCSCC ever reported. As the largest prospective study of definitive RT for LAUCSCC, the data suggest integrating cemi with RT may benefit appropriate pts. Future studies identifying pts who are best served with this approach are warranted. Clinical trial information: NCT05574101 . Response over time. Complete response Partial response Stable disease Progressive disease Non-response/Non-progression 1 NA 2 Time 6w post cemi 1 (3%) 11 (32%) 15 (44%) 3 (9%) 4 (12%) 0 12w post cemi 4 (12%) 15 (44%) 6 (18%) 1 (3%) 4 (12%) 4 (12%) 12w post RT 10 (29%) 10 (29%) 4 (12%) 3 (9%) 4 (12%) 3 (9%) 18m post cemi 11 (32%) 6 (18%) 0 1 (3%) 4 (12%) 12 (35%) 1 Pts with non-target lesions only. 2 Pts not assessed (response assessment pending or not performed because of PD at 6w post cemi, or withdrawal).