Trials of Rintatolimod Across Solid Tumor Types Continue to Advance

Cancer cell in red | Image Credit: © Jezper - www.stock.adobe.com

Multiple studies are currently enrolling patients across tumor types to evaluate the safety and efficacy of rintatolimod (Ampligen).^1-3

Rintatolimod is a dsRNA and highly selective TLR3 agonist immune-modulator with broad spectrum activity being developed as a combinational therapy for the treatment of a variety of solid tumor types and is currently being evaluated in multiple clinical trials.⁴

Pancreatic Cancer

In the first phase 2, randomized, open-label controlled study (NCT05494697), investigators are assessing treatment with rintatolimod vs a control group undergoing no treatment following FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin). Patients will be those aged 18 years and older with locally advanced pancreatic adenocarcinoma (LAPC).¹

Enrollment is open to patients with a histological diagnosis of pancreatic adenocarcinoma confirmed pathologically with measurable disease per RECIST v.1.1, adequate organ function, a life expectancy of ≥ 3 months, and a minimum weight of 40kg at baseline. Patients must have completed 4 or more months of first line FOLFIRINOX with disease progression per RECIST v.1.1 as confirmed by CT or MRI scan 4 to 12 weeks after last FOLFIRINOX treatment.

In the experimental arm, patients will be treated with intravenous (IV) rintatolimod up to 400 mg twice weekly until disease progression. In the control arm, patients with be followed with no treatment until evidence of disease progression.

The primary end point of the study is progression-free survival (PFS), and secondary end points are overall survival (OS), overall response rate, and duration of response.

With a study completion date of January 2027, investigators plan to enroll 90 patients and are actively recruiting in Nebraska and Ohio.

“We are pleased to join into what we believe is an important phase 2 study that has the potential to address a much-needed treatment option for LAPC. Our team is actively working to enroll and treat patients on the study in a joint effort with all other clinical trial sites. We are encouraged by the potential of Ampligen and look forward to further exploring its potential in the treatment of LAPC,” said Kelsey Klute, MD, medical director of the Pancreatic Siseases Specialty Clinic at Nebraska Medicine, in a press release.⁴

Another study in pancreatic cancer is ongoing. The exploratory, non-randomized, open-label, single center, phase 1/2 study (NCT05927142) is assessing the combination of an anti-PD-L1 immune checkpoint inhibitor, durvalumab, with a TLR-3 agonist, rintatolimod, in patients with metastatic pancreatic ductal adenocarcinoma.²

In the experimental arm of the study, durvalumab and rintatolimod combination therapy will be administered to patients. Durvalumab 1500 mg will be administered via IV infusion on day 1 of every 28-day cycles for a total of maximum 12 cycles, and rintatolimod 200-400 mg will be administered via IV infusion 2 times a week for a total of 6 weeks.

Patients will be eligible for enrollment in the study if aged 18 years and older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic cancer and stable disease according to RECIST V.1.1 after 8 or cycles of chemotherapy. Patients will also be included ≤ 6 weeks after stopping treatment with FOLFIRINOX if they have an accessible metastatic lesion for histological tissue collection, weigh >30 kg, and have a WHO performance status of 0-1.

Other requirements include having adequate renal function, bone marrow function, and liver tests, a life expectancy of at least 12 weeks, and agreeing to use effective contraceptive methods.

The primary end point of the phase 1b portion of the study is to determine the safety of the combination. In phase 2, the primary end point seeks to assess the clinical benefit rate of durvalumab plus rintatolimod. For secondary end points, investigators plan to evaluate OS, PFS, the immunogenic effect of the combination on the circulating and infiltrating immune profiles, and the clinical effect of the combination therapy on quality of life using questionnaires.

The study plans to enroll approximately 43 patients and has a study completion date of October 2026.

Breast Cancer

In a phase 1 study (NCT05927142), investigators enrolled patients with triple negative breast cancer (TNBC) to evaluate the safety and tolerability of the combination of rintatolimod and celecoxib with or without interferon alfa-2b, given with chemotherapy.³

The primary end points were safety and tolerability, and to identify the appropriate dose level of chemokine modulation therapy and paclitaxel. Secondary end points were pathologic complete response rate, overall survival, and recurrence-free survival. Additionally, tumor and blood biomarkers were analyzed in exploratory studies.

Previously in November 2022, positive data from the study were presented at the SITC 37th Annual Meeting which showed the chemokine-modulating regimen with rintatolimod to be well-tolerated. Promising clinical activity of pathologic complete response with microinvasive residual disease were also observed.

With the study completed, investigators are now analyzing data and full study results are anticipated to be released before the end of the year.

“We have made promising progress across multiple clinical fronts, and I am proud of the dedication of our team and their evident operational execution. [Rintatolimod] continues to demonstrate significant potential across multiple types of cancers, immune disorders, and viral diseases. We are committed to advancing [rintatolimod’s] development and are poised to achieve multiple key milestones in 2023,” said Thomas K. Equals, chief executive officer of AIM, in a press release.⁴

_REFERENCES:

_{1. Ampligen compared to no treatment following FOLFIRINOX in subjects with locally advanced pancreatic adenocarcinoma. ClinicalTrials.gov. Updated August 9, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05494697?term=Rintatolimod&draw=2&rank=2}

_{2. Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy efficacy (DURIPANC). ClinicalTrials.gov. Updated July 3, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05927142?term=Rintatolimod&draw=2&r}

_{3. Chemokine modulation therapy and standard chemotherapy before surgery for the treatment of early stage triple negative breast cancer. ClinicalTrials.gov. Updated June 2, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04081389}

_{4. AIM ImmunoTech outlines recent significant progress across clinical development pipeline and provides update on positive pre-clinical and IP developments. News release. AIM ImmunoTech Inc. June 12, 2023. Accessed August 9, 2023. https://tinyurl.com/mv8acvd6}