Combining a WT1 vaccine (Galinpepimut-S) with checkpoint inhibition (nivolumab) in patients with WT1–expressing diffuse pleural mesothelioma: A phase 1 study Journal Article
| Authors: | Agrawal, P.; Offin, M.; Lai, V.; Ginsberg, M. S.; Adusumilli, P. S.; Rusch, V. W.; Sauter, J. L.; Ho, T.; Wong, P.; Zauderer, M. G. |
| Article Title: | Combining a WT1 vaccine (Galinpepimut-S) with checkpoint inhibition (nivolumab) in patients with WT1–expressing diffuse pleural mesothelioma: A phase 1 study |
| Abstract: | Introduction: WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non–human leukocyte antigen–restricted, heteroclitic WT1–specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival. Methods: To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity. Results: Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months. Conclusions: Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size. © 2024 The Authors |
| Keywords: | immunotherapy; cancer vaccines; mesothelioma; phase 1 |
| Journal Title: | JTO Clinical and Research Reports |
| Volume: | 6 |
| Issue: | 1 |
| ISSN: | 2666-3643 |
| Publisher: | Elsevier BV |
| Date Published: | 2025-01-01 |
| Start Page: | 100756 |
| Language: | English |
| DOI: | 10.1016/j.jtocrr.2024.100756 |
| PROVIDER: | scopus |
| PMCID: | PMC11721428 |
| PUBMED: | 39802820 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work