Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study
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...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001267 |
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| author | Prashasti Agrawal, MD Michael Offin, MD Victoria Lai, MD Michelle S. Ginsberg, MD Prasad S. Adusumilli, MD, FACS Valerie W. Rusch, MD Jennifer L. Sauter, MD Teresa Ho, BS Phillip Wong, PhD Marjorie G. Zauderer, MD |
| author_facet | Prashasti Agrawal, MD Michael Offin, MD Victoria Lai, MD Michelle S. Ginsberg, MD Prasad S. Adusumilli, MD, FACS Valerie W. Rusch, MD Jennifer L. Sauter, MD Teresa Ho, BS Phillip Wong, PhD Marjorie G. Zauderer, MD |
| author_sort | Prashasti Agrawal, MD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0034144e2d044996bd5490c3031fea92 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-0034144e2d044996bd5490c3031fea922025-01-20T04:17:54ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100756Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 StudyPrashasti Agrawal, MD0Michael Offin, MD1Victoria Lai, MD2Michelle S. Ginsberg, MD3Prasad S. Adusumilli, MD, FACS4Valerie W. Rusch, MD5Jennifer L. Sauter, MD6Teresa Ho, BS7Phillip Wong, PhD8Marjorie G. Zauderer, MD9Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NY, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USAThoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NY, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USAThoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NY, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NYDepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NYDepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NYDepartment of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NYImmune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NYImmune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NYThoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NY, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USA; Corresponding author. Address for correspondence: Marjorie G. Zauderer, MD, 19 Bradhurst Avenue, Suite 2100 North, Hawthorne, NY 10532.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.http://www.sciencedirect.com/science/article/pii/S2666364324001267MesotheliomaCancer vaccinesImmunotherapyPhase 1 |
| spellingShingle | Prashasti Agrawal, MD Michael Offin, MD Victoria Lai, MD Michelle S. Ginsberg, MD Prasad S. Adusumilli, MD, FACS Valerie W. Rusch, MD Jennifer L. Sauter, MD Teresa Ho, BS Phillip Wong, PhD Marjorie G. Zauderer, MD Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study JTO Clinical and Research Reports Mesothelioma Cancer vaccines Immunotherapy Phase 1 |
| title | Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study |
| title_full | Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study |
| title_fullStr | Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study |
| title_full_unstemmed | Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study |
| title_short | Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study |
| title_sort | combining a wt1 vaccine galinpepimut s with checkpoint inhibition nivolumab in patients with wt1 expressing diffuse pleural mesothelioma a phase 1 study |
| topic | Mesothelioma Cancer vaccines Immunotherapy Phase 1 |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001267 |
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