Reference Detail

Ref Type

abstract

PMID

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

Title

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).

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	42	16_suppl	2024		J Clin Oncol

URL

https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6003

Abstract Text

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 oncogenes1. Combination of cemiplimab, an anti-PD-1 antibody with ISA101b elicits a synergistic anti-tumor effect2. 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 <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 <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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	oropharynx cancer	predicted - sensitive	Cemiplimab + ISA101b	Phase II	Actionable	In a Phase II trial, ISA101b and Libtayo (cemiplimab) combination treatment demonstrated safety in patients with HPV16-positive oropharynx cancer and resulted in an overall response rate (ORR) that did not significantly differ from placebo plus Libtayo (cemiplimab) in the full analysis set (25.3 vs 22.9%, p=0.590), but in CD274 (PD-L1)-positive patients in the per protocol set (CPS>/=20), the ORR was significantly improved (61.9 vs 28.0%, p=0.026) (J Clin Oncol 42, 2024 (suppl 16; abstr 6003); NCT03669718).	detail...