Rintatolimod Combo Yields Clinical Benefit in Recurrent Ovarian Cancer

“We look forward to publishing a more detailed analysis of these data in a peer-reviewed clinical journal this summer,” according to Robert Edwards, MD.

Treatment with rintatolimod (Ampligen) plus pembrolizumab (Keytruda) demonstrated a potential improvement in efficacy compared with pembrolizumab monotherapy among patients with recurrent ovarian cancer, according to a press release from developers AIM ImmunoTech on topline findings from a phase 2 trial (NCT03734692).¹

In patients with platinum-sensitive disease who received rintatolimod in combination with pembrolizumab and cisplatin, the objective response rate (ORR) was 45%. Additionally, the treatment yielded a clinical benefit rate (CBR) of 55%. The triplet also produced a median progression-free survival (PFS) of 7.8 months.

“These results are incredibly favorable when compared [with] data from the hallmark phase 2 Keynote-100 study [NCT02674061], which looked at the use of pembrolizumab alone in the treatment of recurrent ovarian cancer [in patients who had] both platinum-resistant and platinum-sensitive [disease],” Robert Edwards, MD, chair of the Department of Obstetrics, Gynecology & Reproductive Sciences and co-director of Gynecologic Oncology Research at the University of Pittsburgh Medical Center Magee-Womens Hospital, said in the press release.¹

According to findings from the Keynote-100 study published in the Journal of Clinical Oncology, the ORR with pembrolizumab monotherapy among a cohort of patients with 2 or fewer prior lines of chemotherapy for recurrent advanced ovarian cancer and a platinum-free or treatment-free interval of 3 to 12 months was 8.1% (95% CI, 5.2%-11.9%).² Edwards stated that the ORR outcomes with the rintatolimod combination represented a greater than 500% increase compared with the Keynote-100 findings.

Findings from the rintatolimod study also highlighted an acute increase in anti-tumor immunity in biomarkers including CXCL9, CXCL10, and CXCL11, which was comparable with prior reports of the drug’s immune-stimulatory effects in other solid tumors such as pancreatic cancer and colorectal cancer.

“We look forward to publishing a more detailed analysis of these data in a peer-reviewed clinical journal this summer,” Edwards added.¹

Developers designed rintatolimod as a highly selective agonist of TLR-3, which is expressed in various immune cells, epithelial cells, and solid tumors. In the single-arm phase 2 study, an estimated population of 45 patients will receive rintatolimod at 200 mg via intraperitoneal injection plus cisplatin at 50 mg/m2 and pembrolizumab intravenously at 200 mg.³

The trial’s primary end point is ORR per RECIST v1.1 criteria. Secondary end points include PFS, changes in CD8-positive cells, and changes in CD3-positive cells.

Patients 18 years and older with first or second peritoneal recurrence of epithelial adenocarcinoma or carcinosarcoma of ovarian, tubal, or peritoneal origin can enroll on the trial. Additional eligibility criteria include having measurable disease per RECIST v1.1 guidelines, completion of prior platinum-containing therapy, an ECOG performance status of 0 or 1, and adequate organ function.

Those who have received prior treatment with anti–PD-1, anti–PD-L1, or anti–PD-L2 agents or prior systemic therapy within 4 weeks before study entry were ineligible for enrollment. Patients were also unable to enroll if they had active central nervous system metastases and/or carcinomatous meningitis.

“These interim data suggest that there may be a massive positive impact on efficacy when [rintatolimod] is combined with pembrolizumab for the treatment of recurrent ovarian cancer,” Thomas K. Equels, chief executive officer at AIM ImmunoTech, said.¹ “Other research suggests a similar effect in other solid tumor types. We therefore see a [rintatolimod] combination therapy as having potential across multiple types of cancers. We look forward to the additional clinical studies underway and planned in many of these types of tumors to further confirm these effects.”

References

1. 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
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. Accessed April 11, 2024. https://tinyurl.com/33yb5vv5