Maintenance with OSE2101 plus FOLFIRI vs FOLFIRI alone after FOLFIRINOX (FFX) induction in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): Primary endpoint results of a randomized TEDOPAM GERCOR D17-01 PRODIGE 63 trial.

4009 Background: OSE2101 is an off the shelf vaccine made of 10 synthetic HLA-A2-restricted peptides targeting 5 tumor associated antigens. This multicenter, randomized, non-comparative, phase II study assessed FOLFIRI ± OSE2101 maintenance in aPDAC Pts without progression after 8 cycles of FFX. Methods: Eligible aPDAC Pts were randomized to FOLFIRI (Arm A) or FOLFIRI + OSE2101 (Arm B: subcutaneous injection on D1, D15, Q4W/6 doses then Q8W to M12 then Q12W up to M24). Stratification factors: tumor stage (locally advanced vs metastatic), best response to FFX (partial or complete response [CR, PR] vs stable disease [SD]), and center. Primary endpoint: overall survival (OS) rate at M12 in evaluable Pts (M12-OS; Fleming 2-stage design, H0: 25%; H1: 50%, 1-sided alpha: 2.5%, power: 90%); secondary endpoints: progression-free survival (PFS; RECIST v1.1), best response, duration of disease control (DDC), and safety. Results: 107 Pts (ITT) were randomized (53/Arm A, 54/Arm B) between 04/2021 and 05/2023. Median age 64 years (range:37-81), 53% men, 69% had metastases, 36%/64% had PR/SD to prior FFX. No evidence of imbalance in Pt characteristics was observed between arms. Median number of OSE2101 injections was 7.5 (1-14). Median treatment duration of FOLFIRI was 5.4 months in both arms. At data cut-off (Dec 9, 2024), median follow-up was 21.4 months with 101 evaluable Pts for M12-OS (49/Arm A, 52/Arm B; 4 consent withdrawals, 1 Pt’s decision, 1 treatment interruption >4 weeks). Number of death events (n/%) was 19/35.8% in Arm A and 18/33.3% in Arm B. M12-OS (95%CI) was 61% (46.2%-74.8%) in Arm A and 65% (50.9%-78.0%) in Arm B. Median (95%CI) OS and PFS (ITT) were 17.3 months (10.6–23.2) and 8.2 months (5.3–11.6) in Arm A, and 15.5 months (12.4–19.3) and 7.8 months (5.4–10.6) in Arm B. Other secondary endpoints are described in Table. Among 33 Pts with SD to prior FFX in Arm B, 6 (18%) had CR/PR (1/5) when adding OSE2101 to FOLFIRI vs 5 (no CR) among 35 Pts in Arm A. In the safety population, 7 SAEs/6 Pts (12%) in Arm A and 22 SAEs/14 Pts (26%) in Arm B were reported. No unexpected SAEs were observed with OSE2101 except 1 inappropriate administration, and no evidence of increased toxicity of FOLFIRI with OSE2101. Conclusions: TEDOPAM met its primary objective with minimal toxicity and positive outcomes of adding OSE2101 cancer vaccine to maintenance FOLFIRI, albeit mitigated by unexpectedly favorable OS in the control arm. Two complete responses were observed when adding OSE2101. Further follow-up is ongoing and translational analysis planned. Clinical trial information: NCT03806309 . ITT Arm AN=53 Arm BN=54 Best response, n (%) CR 0 (0.0) 2 (3.7) PR 12 (22.6) 10 (18.5) SD 28 (52.8) 34 (63.0) Progressive disease (PD) 8 (15.1) 8 (14.8) Missing 5 (9.5) 0 (0.0) DC rate, n (%) 40 (75.5) 46 (85.2) DDC (95% Cl) 8.8 (6.2-12.9) 9.8 (6.8-14.8)