Maintenance OSE2101 Plus FOLFIRI Meets Primary OS End Point in Advanced/Metastatic PDAC

The off-the-shelf neoepitope-based cancer vaccine OSE2101 (Tedopi) in combination with FOLFIRI (5-fluorouracil [5-FU], leucovorin, and irinotecan) met its primary objective of 1-year overall survival rate (OS) in advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), according to topline findings from arm B of the phase 2 TEDOPAM study (NCT03806309).1

The trial showed that patients who did not experience disease progression after 8 cycles of FOLFIRINOX(leucovorin, fluorouracil, irinotecan, and oxaliplatin) induction chemotherapy experienced a statistically significant improvement in 1-year OS with the combination, according to the predefined statistical hypothesis of 25% (H0) vs 50% (H1). Furthermore, minimal toxicity was observed with OSE2101 plus FOLFIRI in the maintenance setting. Additional follow-up and translational analyses are ongoing, and further results will be presented at upcoming medical congresses.

“These are positive results in a non-comparative trial,” Cindy Neuzillet, MD, PhD, chief of the digestive oncology service and a professor of medicine at Curie Cancer Research Institute, Saint-Cloud in Paris, France, stated in a news release. “That said, we need to better understand the contribution of OSE2101 in the context of this combination. A large translational program on tumor tissue, blood, and imaging is ongoing. Additional analysis at a longer time point will also be necessary for more mature survival data. These results underscore the critical need for ongoing research and the development of more effective therapies, especially given the low long-term survival rates in pancreatic cancer. Every step we take brings us closer to making a meaningful impact in the fight against this challenging disease.”

TEDOPAM was a noncomparative study that evaluated OSE2101 plus FOLFIRI or FOLFIRI alone as maintenance therapy following treatment with FOLFIRINOX-based induction chemotherapy in patients with locally advanced or metastatic PDAC.2 To be included in the study, patients needed to be at least 18 years old; have an ECOG performance status of 0 or 1; have an HLA-A2 genotype; have measurable disease per RECIST 1.1 criteria; and have adequate organ function. Eligible patients also needed to have recurrent or advanced disease not amenable to surgery, although prior resection of a primary tumor was permitted; stable disease or a response per RECIST 1.1 following a 4-month course of frontline FOLFIRINOX or modified FOLFIRINOX induction therapy; and a life expectancy of at least 3 months.

Eligible patients (n = 107) were randomly assigned 1:1 to receive intravenous (IV) FOLFIRI (arm A) or IV FOLFIRI plus subcutaneous OSE2101 (arm B) as maintenance therapy. In both arms, the FOLFIRI regimen consisted of 400 mg/m2 of leucovorin, 180 mg/m2 of irinotecan, and a 5-FU bolus at 400 mg/m2 followed by a continuous infusion at 2400 mg/m2 per 46 hours. OSE2101 was administered on days 1 and 15 every 4 weeks for 6 doses then every 8 weeks until month 12 followed by every 12 weeks for a maximum treatment duration of 24 months. Treatment in both arms continued until disease progression or unacceptable toxicity.

Secondary end points included progression-free survival, success of the strategy rate, treatment-related adverse effects, objective response rate, and health-related quality of life.

“The initial results provide a glimmer of hope in the fight against advanced or metastatic pancreatic cancer,” Nicolas Poirier, CEO, OSE Immunotherapeutics, added in the news release.1 “This disease is notoriously difficult to treat, and the need for effective therapies is urgent. These early results show potential promising benefit in some subsets of patients; further research and analysis are needed to confirm their impact. These additional positive results in a randomized clinical trial represent another step forward for the development of OSE2101 and more broadly, these data provide more evidence for the therapeutic cancer vaccine modality.”

References

1. OSE Immunotherapeutics and GERCOR announce positive topline phase 2 result for clinical trial TEDOPaM evaluating OSE2101 (Tedopi®) in advanced pancreatic cancer. News release. OSE Immunotherapeutics. March 11, 2025. Accessed March 12, 2025. https://www.ose-immuno.com/wp-content/uploads/2025/03/EN_250311_TEDOPaM_VFinal.pdf
2. Maintenance with OSE2101 plus FOLFIRI, or FOLFIRI after FOLFIRINOX-based induction therapy in locally advanced or metastatic pancreatic ductal adenocarcinoma (TEDOPAM). ClinicalTrials.gov. Updated February 27, 2023. Accessed March 12, 2025. https://clinicaltrials.gov/study/NCT03806309