Phase I study of a multivalent WT1 peptide vaccine (galinpepimut-S) in combination with nivolumab in patients with WT1-expressing ovarian cancer in second or third remission Journal Article
| Authors: | Manning-Geist, B. L.; Gnjatic, S.; Aghajanian, C.; Konner, J.; Kim, S. H.; Sarasohn, D.; Soldan, K.; Tew, W. P.; Sarlis, N. J.; Zamarin, D.; Kravetz, S.; Laface, I.; Rasalan-Ho, T.; Qi, J.; Wong, P.; Sabbatini, P. J.; O’Cearbhaill, R. E. |
| Article Title: | Phase I study of a multivalent WT1 peptide vaccine (galinpepimut-S) in combination with nivolumab in patients with WT1-expressing ovarian cancer in second or third remission |
| Abstract: | We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade ≥3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate. © 2023 by the authors. |
| Keywords: | adult; clinical article; controlled study; human tissue; protein expression; aged; human cell; clinical feature; drug tolerability; fatigue; diarrhea; drug efficacy; drug safety; treatment duration; progression free survival; ovary cancer; protein targeting; arthralgia; injection site reaction; pneumonia; pruritus; rash; cancer regression; immune response; immunotherapy; antigens; immunoglobulin g; immunogenicity; immunophenotyping; phase 1 clinical trial; wt1 protein; hypothyroidism; epithelial ovarian cancer; alopecia; vaccine; myositis; myocarditis; nivolumab; human; article; programmed cell death 1 receptor; vaccine immunogenicity; galinpepimut s |
| Journal Title: | Cancers |
| Volume: | 15 |
| Issue: | 5 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2023-03-01 |
| Start Page: | 1458 |
| Language: | English |
| DOI: | 10.3390/cancers15051458 |
| PROVIDER: | scopus |
| PMCID: | PMC10001251 |
| PUBMED: | 36900251 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Roisin E. O’Cearbhaill -- Source: Scopus |
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