Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1-Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study

Our plain-English summary of Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1-Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study, by P. Agrawal, M. Offin, V. Lai, et al (JTO Clinical and Research Reports, 2025).

The study

• Authors: P. Agrawal, M. Offin, V. Lai, M.S. Ginsberg, P.S. Adusumilli, V.W. Rusch, J.L. Sauter, T. Ho, P. Wong, M.G. Zauderer
• Journal: JTO Clinical and Research Reports
• Published: 2025;6(1):100756
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a single-center, open-label, nonrandomized phase 1 trial at Memorial Sloan Kettering Cancer Center. It tested a WT1 peptide vaccine, galinpepimut-S (GPS), combined with the immunotherapy drug nivolumab. Ten patients were treated. All had diffuse pleural mesothelioma that had progressed or come back after pemetrexed-based chemotherapy. Two of the 10 reported classical occupational asbestos exposure; the article did not name fiber types. Seven of the 10 patients had at least one adverse event, and there were four toxicities of grade 3 or higher. One patient had grade 4 lung infection and pneumonitis possibly attributed to nivolumab and later died of sepsis. Three of the 10 patients (30%) showed vaccine-specific T-cell responses. Tumor response could be assessed in eight patients. None had a partial response, and three had prolonged stable disease with up to a 17% decrease in tumor volume. Median progression-free survival was 3.9 months, and median overall survival from enrollment was 7.4 months. The authors concluded the combination stimulated vaccine-specific immune responses but not radiographic anticancer activity. They named the small study size as a limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center, open-label, nonrandomized phase 1 clinical trial
• Who was studied: Ten patients at Memorial Sloan Kettering Cancer Center with WT1-positive diffuse pleural mesothelioma that was progressive or recurrent after pemetrexed-based chemotherapy
• Exposure: Treatment with the WT1 peptide vaccine galinpepimut-S every 2 weeks on weeks 0 to 14, plus intravenous nivolumab every 2 weeks on weeks 4 to 14
• Main results:
  • Two of the 10 patients (20%) had a history of self-reported classical occupational asbestos exposure; no fiber type was given
  • The authors reported that the study met its primary end point: the combination was safe and well tolerated
  • Seven of the 10 patients (70%) had at least one adverse event, and five (50%) had more than one
  • Across all patients there were seven grade 1, three grade 2, and four grade 3 or higher toxicities
  • One patient had grade 4 lung infection and pneumonitis possibly attributed to nivolumab
  • That patient later died of sepsis from Enterococcus faecalis
  • Three of the 10 patients (30%) had vaccine-specific T-cell responses
  • None of the three patients with immune responses had self-reported classical occupational asbestos exposure
  • Best overall tumor response could be assessed in eight patients
  • There were no partial responses; three patients had prolonged stable disease with up to a 17% decrease in tumor volume
  • For all patients, median progression-free survival was 3.9 months and median overall survival from enrollment was 7.4 months
• The authors' conclusion: The authors concluded that the combination of GPS and nivolumab stimulated vaccine-specific immunogenicity but not radiographic anticancer activity in patients with diffuse pleural mesothelioma
• Limitations the authors state:
  • The small study size limited the authors' ability to correlate disease outcomes with immune response data
  • Not all patients had enough blood samples for immune testing at multiple time points

Topics

Medical terms in this study, explained in our Lexicon: Galinpepimut-S (WT1), Nivolumab (Opdivo), Pleural Mesothelioma, Clinical Trial, Tumor Microenvironment, Median Overall Survival, Monoclonal Antibody, Pemetrexed (Alimta).

Related studies

• Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses — J.E. Reuss, P.K. Lee, et al. (2025)
• Combining Chemotherapeutic Agents, Targeted Therapies, Vaccines and Natural Bioactive Compounds for Mesothelioma: Advances and Perspectives — R. Carrano, C. Zucca, et al. (2025)
• Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate — Y. Sakurai, A. Kato, et al. (2019)
• A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma — A. Rimner, P.S. Adusumilli, et al. (2023)
• A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4 — L. Cheng, X. Tang, et al. (2022)
• Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine — S. Thunold, E. Hernes, et al. (2025)

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