A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma

Abstract

Purpose Determine the 1-year progression-free survival (PFS) among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy vs those receiving control adjuvants. Patients and Methods This double-blind, controlled, two center phase II trial randomized MPM patients after surgery and another treatment modality to galinpepimut-S with GM-CSF and Montanide or GM-CSF and Montanide alone. An improvement in 1-year PFS from 50% to 70% was the predefined efficacy threshold, and 78 patients total were planned. The study was not powered for comparison between the two arms. Results 41 patients were randomized. Treatment related adverse events were mild, self-limited, and not clinically significant. Based on a stringent prespecified futility analysis (futility = ≥ 10 of 20 patients on one arm experiencing progression < 1 year), the control arm closed early. The treatment arm was subsequently closed because of the resultant unblinding. The PFS rate at 1 year from beginning study treatment was 33% and 45% in the control and vaccine arms, respectively. Median PFS was 7.4 months vs 10.1 months and median OS was 18.3 months vs 22.8 months in the control and vaccine arms, respectively. Conclusion The favorable safety profile was confirmed. PFS and OS were greater in those who received vaccine but the trial was neither designed nor powered for comparison between the arms. Based on these promising results, the investigators are planning a larger randomized trial with greater statistical power to define the optimal use and benefit of galinpepimut-S in the treatment of MPM.

Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation

“…In the adjuvant space, interventions with vaccines may have promise. Galinpepimut-S Wilms tumor 1 vaccine was randomized against placebo in a double-blind trial 31 ; when administered after macroscopic complete resection, the vaccine demonstrated superiority over control. The median progressionfree survival (PFS) was 7.4 months versus 10.1 months, and the median overall survival (OS) was 18.3 months versus 22.8 months in the control and vaccine arms, respectively.…”

Malignant Mesothelioma: Has Anything Changed?

“…Although the control arm was closed early due to a prespecified futility analysis and the trial was not powered for comparison between the two arms, the median PFS (10.1 vs. 7.4 months) and median OS (22.8 vs. 18.3 months) favored patients who received the WT-1 vaccine. 142 Dendritic cell-based immunotherapy involves pulsing autologous harvested dendritic cells ex vivo with tumor lysate followed by dendritic cell vaccination to generate a tumor-specific immune response. Hegmans et al demonstrated safety, feasibility, and induction of an antitumor immunological response in MPM patients treated with dendritic cell vaccine and chemotherapy.…”

Reader‑free ELISPOT assay for immuno‑monitoring in peptide‑based cancer vaccine immunotherapy

“…The WT1 protein is highly immunogenic (29). Immunotherapies targeting WT1 have been developed in a number of countries as novel, promising therapeutic strategies for various types of cancer such as leukemia, glioblastoma and pancreatic cancer (30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”