793P NeoPeLe: A phase II trial of neoadjuvant (NAT) pembrolizumab (Pembro) combined with lenvatinib (Lenva) in resectable stage III melanoma

Abstract

Neoadjuvant anti-PD-1 (PD1) induces a pathological complete response (pCR) in 20% and any pathological response (pRR) in 34% of stage III pts, with durable survival in responders. Improvements are needed to overcome primary resistance. NeoPele sought to determine if additional clinical benefit can be achieved by adding lenva to pembro using the NAT platform in pts with stage III melanoma (NCT04207086). 20 pts with resectable, RECIST measurable stage III nodal melanoma received 6 wks of NAT with pembro (200mg, IV, Q3W) and lenva (20mg, po, od), then a lymph node dissection (LND), then 46 wks pembro. CT + PET scans were performed at baseline and wk 6; CT was continued 12 wkly to 2 yrs. Primary endpoint was pCR and pRR at wk 6. Secondary endpoints; RECIST RR at wk 6, event-free survival (EFS), relapse free survival (RFS), OS, toxicity and translational endpoints. At data cut off 31 Mar 2022, 20 pts analysed: 30% female, med age 64.7 yrs, 3 (15%) BRAF V600E, 8 (40%) NRAS, 10 (50%) clinical N1b. Med f/u was 11.2 months (95% CI 10.2 - 13.8). 8/20 (40%) pts had pCR and 15/20 (75%) had any path response (Table). Events occurred in 4 pts; 1 had brain metastasis prior to LND with pPR, and 3 post surgery with pNR. Most common toxicities were fatigue (9, 45%), hypertension (8, 40%), headache (6, 30%) and anorexia (5, 25%) due to lenva; 45% were gd 3/4, most commonly hypertension (5, 25%). Most common surgical events were seroma (4, 20%) and lymphoedema (7, 35%), with no DVTs. 4 pts interrupted lenva and 0 permanently discontinued during NAT. Post NAT surgical operability was the same or improved in 13 (65%) pts, and harder in 7 (35%). Longitudinal analysis of melanoma tissue, microenvironment and microbiome is ongoing.Table: 793PPembro+Lenva (n=20)pRR pCR Near pCR pPR pNR15 (75%) 8 (40%) 3 (15%) 4 (20%) 5 (25%)RECIST ORR/CR35% / 5%No. Events4 (20%)No. Recurred/Progressed by pCR/near-pCR/pPR/pNR0/0/1ˆ/3No. Death11-yr EFS (95% CI)80% (95% CI 64-99%)ˆ1 pt progressed in brain prior to surgery but had LND. Open table in a new tab ˆ1 pt progressed in brain prior to surgery but had LND. A high pCR and pRR rate was observed with NAT pembro+lenva, higher than previous studies of PD1 alone. The trial and translational investigations are ongoing, and RFS and OS data will be collected.