Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial Journal Article
| Authors: | Gupta, A.; O'Cearbhaill, R. E.; Block, M. S.; Hamilton, E.; Konner, J. A.; Knutson, K. L.; Potts, J.; Garrett, G.; Kenney, R. T.; Wenham, R. M.; for the TPIV200 Ovarian Cancer Study Investigators |
| Article Title: | Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial |
| Abstract: | Objective: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy. Methods: We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS). Results: At study termination with a median follow-up of 15.2 months (range 1.2–28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3–16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event. Conclusion: TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222. © 2024 Elsevier Inc. |
| Keywords: | adult; controlled study; treatment response; aged; unclassified drug; major clinical study; overall survival; constipation; drug tolerability; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; side effect; cancer patient; follow up; ovarian cancer; progression free survival; antineoplastic metal complex; multiple cycle treatment; neutrophil count; pain; phase 2 clinical trial; nausea; randomized controlled trial; stomatitis; myalgia; arthralgia; dizziness; fever; injection site reaction; pruritus; rash; maculopapular rash; malaise; cancer vaccine; multicenter study; vaccination; acne; ovary carcinoma; erythema; limb pain; dermatitis; headache; hot flush; leukocyte count; hypothyroidism; peptide vaccine; gastroesophageal reflux; double blind procedure; muscle spasm; alopecia; disease exacerbation; injection site erythema; thyrotropin; dysgeusia; joint stiffness; folate receptor alpha; gm-csf; dysphonia; thyrotropin blood level; folate receptor 1; injection site pruritus; musculoskeletal pain; hypersalivation; contusion; intention to treat analysis; human; female; article; sargramostim; body temperature disorder; multi-epitope vaccine; tpiv 200; generalized pruritus; injection site mass |
| Journal Title: | Gynecologic Oncology |
| Volume: | 189 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-10-01 |
| Start Page: | 90 |
| End Page: | 97 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2024.07.675 |
| PUBMED: | 39068739 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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