# A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol® in Patients with Recurrent Platinum-Resistant Ovarian Cancer

## TL;DR

This study tested a new treatment combining immunization and immune stimulation in patients with platinum-resistant ovarian cancer, showing some safety and potential anti-tumor effects.

## Contribution

The study demonstrates the safety and compatibility of combining oregovomab immunization with Hiltonol® in platinum-resistant ovarian cancer patients.

## Key findings

- Median progression-free survival was 2.7 months and overall survival was 15 months.
- Adverse events were mostly mild, including fatigue and injection site discomfort.
- Early humoral response was observed in 77% of patients by week 6.

## Abstract

This phase Ib study assessed the safety and compatibility of indirect oregovomab immunization and Toll-like-receptor-3 stimulation with immune adjuvant Hiltonol® and induced clinically relevant cancer antigen-125-specific anti-tumor immunity in heavily pretreated patients with platinum-resistant ovarian cancer. Patients with elevated serum CA125 level > 50 U/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol® 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’s discretion. Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen patients completed at least three Hiltonol® infusions with oregovomab. Adverse events included mild fatigue, flu-like symptoms, chills, axillary pain, and injection site discomfort. Treatment-related serious adverse events included hypertension (n = 2) and low platelets (n = 1). Median progression-free survival and overall survival were 2.7 and 15 months, respectively. This study demonstrated safety and compatibility.

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® (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 >50 U/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol® 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’s discretion. The Fifth/final oregovomab with Hiltonol® infusion was given at week 16. Results: Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen (87%) patients completed at least three Hiltonol® 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: 8.2–23.9). Conclusions: The safety and compatibility of combining oregovomab with Hiltonol® have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol® stimulation is proposed.