{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:39Z","timestamp":1760060739032,"version":"build-2065373602"},"reference-count":15,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"OncoQuest Pharmaceuticals, Inc., Edmonton, AB, Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Objectives: This phase Ib study assessed the safety and compatibility of indirect oregovomab immunization and Toll-like-receptor-3 (TLR3) stimulation with immune adjuvant Hiltonol\u00ae (poly-ICLC) and induced clinically relevant CA125-specific anti-tumor immunity in heavily pretreated patients with progressive platinum-resistant ovarian cancer (PROC). Methods: Patients with elevated serum CA125 level &gt;50 U\/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol\u00ae intramuscular 30 min and 48 h post-oregovomab at weeks 0, 3, 6, and 9. At week 12, imaging was performed, and salvage chemotherapy was allowed post-progression per the investigator\u2019s discretion. The Fifth\/final oregovomab with Hiltonol\u00ae infusion was given at week 16. Results: Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen (87%) patients completed at least three Hiltonol\u00ae infusions with oregovomab, specifically, two cycles (n = 2), three cycles (n = 2), four cycles (n = 3), and five cycles (n = 8). Adverse events included mild fatigue, flu-like symptoms, chills, axillary pain, and injection site discomfort in 13 (87%) patients. Serious adverse events were reported in seven (47%) patients, including Grade 3 hypertension (n = 2), thrombocytopenia (n = 1), and Grade 3 events attributed to underlying disease (n = 4). Ten (67%) patients had disease progression, three (20%) had stable disease, and two were unevaluable. Early humoral response by week 6 was observed in seven of nine (77%) patients, median progression-free survival was 2.7 months (95% confidence interval [CI]: 2.2, 3.3), and median overall survival was 15.0 months (95% CI: 8.2\u201323.9). Conclusions: The safety and compatibility of combining oregovomab with Hiltonol\u00ae have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol\u00ae stimulation is proposed.<\/jats:p>","DOI":"10.3390\/curroncol32100532","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:19:45Z","timestamp":1758701985000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol\u00ae in Patients with Recurrent Platinum-Resistant Ovarian Cancer"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3121-4605","authenticated-orcid":false,"given":"Robert W.","family":"Holloway","sequence":"first","affiliation":[{"name":"Gynecologic Oncology Program, AdventHealth Cancer Institute, Orlando, FL 32804, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2745","authenticated-orcid":false,"given":"Sarah M.","family":"Temkin","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0443-5573","authenticated-orcid":false,"given":"Sarah W.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil","family":"Gupta","sequence":"additional","affiliation":[{"name":"CanariaBio, Inc., Seoul 06044, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivasa R.","family":"Jada","sequence":"additional","affiliation":[{"name":"CanariaBio, Inc., Seoul 06044, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5180-0409","authenticated-orcid":false,"given":"Sarfraz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Program, AdventHealth Cancer Institute, Orlando, FL 32804, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William P.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.ygyno.2004.04.024","article-title":"CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients","volume":"94","author":"Gordon","year":"2004","journal-title":"Gynecol. 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Immunother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.ygyno.2019.12.024","article-title":"Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study","volume":"156","author":"Brewer","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/13543784.2021.1868436","article-title":"Oregovomab: An investigational agent for the treatment of advanced ovarian cancer","volume":"30","author":"Pietragalla","year":"2021","journal-title":"Expert Opin. Investig. 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