A combination therapy of rintatolimod (Ampligen) and durvalumab (Imfinzi) has shown early signs of disease control and a favorable safety profile in patients with late-stage pancreatic cancer, according to initial findings from the phase 1b/2 DURIPANC trial (NCT05927142). The results offer a potential new avenue for treating this aggressive malignancy, where treatment options remain limited.
The DURIPANC trial, a single-center, open-label, nonrandomized study, is evaluating the combination in patients with metastatic pancreatic cancer who have achieved stable disease following at least 8 cycles of FOLFIRINOX. Patients enrolled within 6 weeks of stopping FOLFIRINOX and had an accessible metastatic lesion for histological tissue collection.
Early Disease Control
According to the preliminary data, 2 out of 3 patients in the first dose level cohort experienced stable disease at 6 months and continued treatment, with disease progression being assessed every 3 months. An additional cohort of 2 out of 3 patients at a higher dose also showed stable disease, though they have not yet reached the 6-month assessment mark. Progression-free survival data are pending, as the initial cohort has not yet experienced disease progression.
Casper H.J. van Eijck, MD, PhD, a pancreato-biliary surgeon at Erasmus Medical Center and coordinating investigator for the DURIPANC study, noted the significance of these early findings. "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," he stated. He further emphasized the contrast with typical outcomes, noting that approximately 80% of similar patients at Erasmus without the treatment showed disease progression after just 3 months.
Tolerability and Safety
Prior data from the DURIPANC trial indicated that the combination of rintatolimod and durvalumab was generally well-tolerated. The first cohort in the dose-escalation phase experienced no severe adverse effects (AEs) or dose-limiting toxicities (DLTs).
Study Design and Endpoints
The DURIPANC trial enrolled patients aged 18 years or older with histologically confirmed metastatic pancreatic cancer and a WHO performance status of 0 to 1. Key exclusion criteria included active autoimmune disease, prior treatment with immunotherapeutic drugs, and significant ascites or pleural effusion.
Patients receive durvalumab at 1500 mg on day 1 of each 28-day cycle for a maximum of 12 infusions, combined with rintatolimod at 200 mg to 400 mg twice per week for 6 weeks, totaling 12 infusions. The primary endpoint for phase 1b is determining the recommended phase 2 dose based on DLTs. The primary endpoint for phase 2 is the clinical benefit rate of the combination.
Optimism for Future Responses
Dr. van Eijck expressed optimism about the potential for more significant responses. "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."
