Rintatolimod-Based Regimen Hits 50% Response Rate in Ovarian Cancer

Combining intraperitoneal (IP) rintatolimod (Ampligen) with pembrolizumab (Keytruda) and cisplatin led to a 50% objective response rate (ORR) in patients with platinum-sensitive recurrent ovarian cancer, according to updated data from a phase 2 trial from the University of Pittsburgh Medical Center (UPMC; NCT03734692).¹

Of the 27 patients enrolled in the trial, 24 were evaluable for response. Among those 24, 5 achieved a complete response and seven achieved a partial response, yielding a confirmed ORR of 50%. The clinical benefit rate reached 79%. Median overall survival was 32.5 months, with select patients achieving durable responses exceeding 70 months.¹

The study demonstrated the potential of rintatolimod, a first-in-class double-stranded RNA and highly selective TLR-3 agonist, to synergistically boost outcomes with immunotherapies such as pembrolizumab in ovarian cancer. Outcomes with single-agent checkpoint inhibition have historically been low in ovarian cancer. Outcomes from the KEYNOTE-100 study showed an ORR of 8.1% with single-agent pembrolizumab in patients with advanced recurrent ovarian cancer.²

Regarding safety in the phase 2 UPMC trial, there were no grade 4 or 5 toxicities observed. Collection of data for progression-free survival, overall survival, and time to disease progression remain ongoing with the anticipated analysis completion target of January 2027.

“This single-arm phase 2 trial is the third in a series of consecutive studies evaluating IP chemotherapy or chemoimmunotherapy using this analytical approach. The addition of IP Ampligen and systemic PD-1 checkpoint inhibition to IP cisplatin chemotherapy resulted in a significant improvement in both clinical response rates and immune activation across highly comparable patient cohorts in the 3 trials,” Robert P. Edwards, MD, McCall Chair of Obstetrics, Gynecology, and Reproductive Science at the University of Pittsburgh School of Medicine, stated in a news release.¹

Study Design

The single-arm phase 2 UPMC trial enrolled patients with first or second peritoneal recurrence of platinum-sensitive epithelial ovarian, tubal, or peritoneal cancer with measurable disease per RECIST 1.1 criteria. Patients had an ECOG performance status of 0 or 1 and had completed prior platinum-containing therapy.

The regimen consisted of rintatolimod at 200 mg administered intraperitoneally over 1 to 2 hours, cisplatin at 50 mg/m² intraperitoneally, and pembrolizumab at 200 mg intravenously — delivered in up to 6 cycles at 3-week intervals, followed by interval cytoreduction approximately 4 weeks after the fourth cycle, and then 2 consolidation cycles postsurgery.³

An earlier interim analysis of the UPMC trial had shown an ORR of 45%, a clinical benefit rate of 55%, and a median PFS of 7.8 months.⁴

“These results represent what we believe is a strong step forward in the potential to enhance treatment of recurrent ovarian cancer, if further studies support findings of relatively low toxicity, clinical benefit and durable response. Once again, data suggests that Ampligen may unlock the full potential of checkpoint immunotherapies. We are particularly encouraged by the durability of the observed responses. This supports our proposition that Ampligen has the potential to play a major role in solid tumor immuno-oncology—expanding the number of patients who benefit from checkpoint inhibitors across multiple cancer types, including ovarian cancer and pancreatic cancer. With strong intellectual property protection extending into 2039 and a growing body of positive clinical evidence, we believe we are well positioned to advance Ampligen into later-stage development and strategic partnerships,” Thomas K. Equels, chief executive officer of AIM ImmunoTech, the developer of rintatolimod, stated in the news release.¹

REFERENCES

1. AIM ImmunoTech Inc. AIM ImmunoTech announces 50% objective response rate (ORR) in UPMC recurrent ovarian cancer phase 2 clinical trial, suggesting breakthrough combination potential. Globe Newswire. Published May 7, 2026. https://tinyurl.com/ybtn8kup

2. Matulonis UA, Shapira R, Santin A, et al. Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer. J Clin Oncol. 2020;38(suppl 15):6005. doi:10.1200/JCO.2020.38.15_suppl.6005

3. Systemic immune checkpoint blockade and intraperitoneal chemo-immunotherapy in recurrent ovarian cancer. ClinicalTrials.gov identifier: NCT03734692. https://clinicaltrials.gov/study/NCT03734692

4. AIM ImmunoTech announces positive top-line, protocol-planned interim report data from the study of Ampligen combined with pembrolizumab for the treatment of recurrent ovarian cancer. News release. AIM ImmunoTech, Inc. April 10, 2024. Accessed April 11, 2024. https://tinyurl.com/ytd6uyc2