Results of a randomized, double-blind, placebo-controlled, phase 2 study (OpcemISA) of the combination of ISA101b and cemiplimab versus cemiplimab for recurrent/metastatic (R/M) HPV16-positive oropharyngeal cancer (OPC).
Authors: Caroline Even, Kevin Joseph Harrington, Erminia Massarelli, Marielle Klein Hesselink, Sonja Visscher, Matthew G. Fury, Femke Sanders, Simon Laban, Jerome Fayette, Marc Oliva, Lisa F. Licitra, Bohuslav Melichar, Anthony Kong, Lot A. Devriese, Irene Brana, Petra Jankowska, Marshall R. Posner, Leon W. Hooftman, Cornelis JM Melief, Renata Ferrarotto
Journal: Journal of Clinical Oncology (2024)

6003 Background: ISA101b (peltopepimut-S) is a therapeutic vaccine targeting the HPV16 E6/E7 oncoproteins. The synthetic long peptides of ISA101b induce specific expansion of both CD4 + T-helper cells and CD8+ cytotoxic T-cells against E6/7 oncogenes 1 . Combination of cemiplimab, an anti-PD-1 antibody with ISA101b elicits a synergistic anti-tumor effect 2 . Methods: First and second line anti-PD-1 naïve patients with confirmed HPV16+ R/M OPC were randomized to treatment with either ISA101b (subcutaneously 100µg/peptide on days 1, 29, and 50) or placebo, with cemiplimab (intravenously 350mg q/21 days) for up to 24 months or until disease progression or treatment withdrawal. The primary efficacy endpoint was ORR after ≥6 months of follow-up by independent review as per RECIST1.1. Data cut-off for this analysis was 5 July 2023. The primary safety endpoint was frequency and severity of AEs. Secondary endpoints included PFS and OS. For the latter 12-month survival data are shown. Combined Positive Score (CPS) analyses were planned subgroup analyses. A p-value &lt;0.1 was defined as statistically significant. Predefined analysis sets are the full analysis set (FAS), i.e. all patients who received ≥1 dose of study drug, and the per protocol set (PPS) which includes patients with centrally confirmed HPV16-positivity who received all 3 doses of ISA101b/placebo, had at least 1 post-baseline tumor assessment and no major protocol deviations. Results: A total of 198 patients (mean age 62.8 ±9.6 years) received ≥1 dose of study drug: 173 (87.4%) male, and 25 (12.6%) female; 110 (55.6%) were treated in first, and 74 (37.4%) in second line. Baseline characteristics were well balanced. In the ISA101b arm, ORR was 25.3% compared to 22.9% in the control arm (NS, Table). SAEs occurred in 33.0% of patients in the ISA101b arm vs 31.6% in the control arm. Patients with a CPS ≥20 treated with cemiplimab and 3 doses of ISA101b had a significantly better ORR and OS compared to patients in the control arm (Table; mOS (95% CI) not reached (28.1, -) vs 23.3 (11.9, 30.1) months, P = 0.0232 (PPS)). Patients with CPS &lt;20 had on average a shorter OS in the ISA101b arm. Conclusions: Whereas there was no advantage of the addition of ISA101b to cemiplimab regarding ORR on the overall population, in patients with CPS ≥20 ISA101b significantly improved the ORR. Median OS was better in patients with CPS ≥20 who completed a full course of ISA101b. In contrast, patients with lower CPS did not benefit. Toxicity was comparable between the 2 arms. Clinical trial information: NCT03669718 . [Table: see text]