Rintatolimod Plus Durvalumab Shows Early Disease Control in Late-Stage Pancreatic Cancer

Treatment with the TLR-3 agonist rintatolimod (Ampligen) in combination with durvalumab (Imfinzi) demonstrated early disease control and safety in patients with late-stage pancreatic cancer, according to preliminary data from the phase 1b/2 DURIPANC trial (NCT05927142).¹

Findings showed that 2 of the 3 patients treated at the first dose level of the combination therapy maintained stable disease at 6 months; these patients will continue to receive treatment and be assessed for disease progression every 3 months. Because 2 of the 3 patients in the first cohort have not experienced disease progression, progression-free survival data have not yet been reported.

Additionally, 2 of 3 patients have been treated in the second cohort at a higher dose and have stable disease; however, these patients have yet to reach the 6-month stability assessment timepoint. The treatment and assessment of these patients are ongoing.

“We have observed improvements in quality of life [QOL] and we saw no toxicity at all—with ‘QOL’ recognized as an indicator of stable disease. As a comparison, approximately 80% of patients at Erasmus with similar disease, but who did not receive the treatment, showed disease progression after only 3 months,” Casper H.J. van Eijck, MD, PhD, pancreato-biliary surgeon at Erasmus Medical Center in Rotterdam, Netherlands, and coordinating investigator for the DURIPANC study, stated in a news release. “[Although] these new data are extremely preliminary, it is also highly encouraging. To have multiple patients with metastatic pancreatic cancer who still have stable disease after 6 or 7 months of maintenance therapy is remarkable—as is having stable disease for 15 or more months after starting FOLFIRINOX. Based on the changes we have seen in immune infiltration into metastatic lesions, I am optimistic that there is a chance that these patients could still have partial or complete responses to this therapy.”

Previously reported data from DURIPANC showed that the combination of rintatolimod and durvalumab was generally well tolerated. No patients treated in the first cohort of the dose-escalation portion of the trial experienced severe adverse effects (AEs) or dose-limiting toxicities (DLTs).²

DURIPANC is a single-center, open-label, nonrandomized trial enrolling patients at least 18 years of age and a body weight of at least 30 kg with histologically or cytologically confirmed metastatic pancreatic cancer who have stable disease per RECIST 1.1 criteria after at least 8 cycles of FOLFIRINOX. Patients must be enrolled within 6 weeks of stopping FOLFIRINOX and have an accessible metastatic lesion for histological tissue collection. Other key inclusion criteria consist of a WHO performance status of 0 to 1; adequate renal function, liver tests, and bone marrow function; and a life expectancy of at least 12 weeks.³

Key exclusion criteria include Child-Pugh grade B/C disease; current treatment with immunotherapeutic drugs; malignant ascites or pleural effusion; active autoimmune disease that has required systemic treatment in past 2 years; prior randomization or treatment in a previous durvalumab clinical trial, irrespective of treatment arm; and any anticancer therapy within 28 days of first study treatment If sufficient wash-out time has not occurred.

Patients are being treated with 1500 mg of durvalumab on day 1 of each 28-day cycle for a maximum of 12 infusions in combination with rintatolimod at 200 mg to 400 mg twice per week for a total of 6 weeks and 12 infusions.

During phase 1b, the primary end point is determining the recommended phase 2 dose, defined as the highest dose without DLTs. In phase 2, the primary end point will be the clinical benefit rate of the combination.

References

1. AIM ImmunoTech reports positive preliminary data in phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer. News release. AIM ImmunoTech. September 19, 2024. Accessed September 19, 2024. https://aimimmuno.com/aim-immunotech-reports-positive-preliminary-data-in-phase-1b-2-study-of-ampligen-and-imfinzi-as-a-combination-therapy-for-late-stage-pancreatic-cancer/
2. AIM ImmunoTech announces first dose level is generally well-tolerated in phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer. News release. AIM ImmunoTech. April 29, 2024. Accessed September 19, 2024. https://aimimmuno.com/aim-immunotech-announces-first-dose-level-is-generally-well-tolerated-in-phase-1b-2-study-of-ampligen-and-imfinzi-as-a-combination-therapy-for-late-stage-pancreatic-cancer/
3. 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 January 19, 2024. Accessed September 19, 2024. https://clinicaltrials.gov/study/NCT05927142