Phosphorus-32 Plus FOLFIRINOX Meets Primary End Points in Locally Advanced Pancreatic Cancer

The addition of intratumoral phosphorus-32 (P-32) microparticles (OncoSil) to FOLFIRINOX chemotherapy met the co-primary end points of 16-week local disease control rate (LDCR) and safety/tolerability in patients with unresectable, locally advanced pancreatic adenocarcinoma, according to data from the phase 2 TRIPP-FFX trial (NCT05466799) presented during the 2026 ESMO Gastrointestinal Cancers Congress.¹

In the intention-to-treat (ITT) population, LDCR at 16 weeks by blinded independent central review was 82.2% (95% CI, 67.9%-92.0%) with FOLFIRINOX plus P-32 microparticles (n = 45) and 86.0% (95% CI, 72.1%-94.7%) with FOLFIRINOX alone (n = 43; P = .0002). In the per-protocol population, the 16-week LDCR rates were 85.0% (95% CI, 70.2%-94.3%) vs and 85.4% (95% CI, 70.8%-94.4%), in the investigational (n = 40) and control (n = 41) arms, respectively (P = .0001).

How was TRIPP-FFX designed?

TRIPP-FFX enrolled adults with histologically or cytologically confirmed, unresectable, locally advanced pancreatic adenocarcinoma (per NCCN 2023 v2 criteria) who had a Karnofsky performance status (KPS) of 70 or higher, had received no prior chemotherapy or radiotherapy, and were fit to receive combination chemotherapy.^1,2

Patients were randomly assigned 1:1 to FOLFIRINOX alone or FOLFIRINOX plus P-32 microparticles, stratified by FOLFIRINOX or modified FOLFIRINOX regimen and by KPS (100-90 vs 80-70).¹Patients received up to 12 cycles of FOLFIRINOX, with continuation at investigator discretion; those in the combination arm underwent planned P-32 microparticle implantation at week 4, with activity calculated by tumor volume to deliver a 100 Gy absorbed dose.

The co-primary end points were safety/tolerability and LDCR at 16 weeks. The trial enrolled across 14 sites in Australia, Belgium, Italy, Spain, and the UK, and was designed to meet the clinical evidence requirements for existing CE Mark registration of the device under the European Union Medical Device Regulation.

Of 119 patients screened, 31 were screen failures and 88 were randomly assigned to the ITT population. Protocol deviations occurred in 2 patients in the FOLFIRINOX arm and 5 in the combination arm, most commonly due to metastatic disease identified after enrollment that precluded P-32 implantation. The per-protocol population comprised 41 and 40 patients, respectively, and the safety population comprised 46 and 41 patients, respectively.

Baseline characteristics were broadly similar between arms, including median age (63.0 [range, 41-81] vs 65 years [range, 42-79]), target tumor longest diameter (35.5 mm [range, 15.2-72] vs 36.3 mm [range 14.8-69]), and target tumor volume (12 cc [range, 1-41] vs 13 cc [range, 1-58]). Median cycles of FOLFIRINOX received were 11 (range, 0-25) vs 12 (range, 1-22), with a cumulative multi-agent relative dose intensity of 75.9% vs 67.9%; all 40 evaluable patients in the combination arm received P-32 microparticle implantation to the target tumor.

What were the additional efficacy data?

Secondary efficacy end points numerically favored the P-32 microparticles combination in the ITT population, including objective response rate (55.6% vs 37.2%), median local progression-free survival (PFS; 12.8 months vs 11.8 months), median PFS (12.1 vs 9.9 months), and median overall survival (OS; 18.2 months vs 15.8 months). Surgical resection occurred in 11.1% vs 11.6% of patients, respectively, with R0 margins achieved in 60% vs 16.7% of resected patients. Median maximal tumor volume decrease was −72.1% with the combination vs −57.0% with FOLFIRINOX alone.

What did the safety analysis show?

Any-grade adverse effects (AEs) occurred in 97.8% of patients treated with FOLFIRINOX alone and 100% of those who received the P-32 microparticles combination; grade 3 or higher AEs occurred in 60.9% and 70.7% of patients, respectively. The most common grade 3 or higher AEs with the combination included neutropenia or decreased neutrophil count (24.4% vs 15.2% with FOLFIRINOX alone), diarrhea (9.8% vs 8.7%), abdominal pain (9.8% vs 6.5%), and increased transaminases (9.8% vs 8.7%).

Grade 3 or higher AEs attributed to chemotherapy occurred in 63.4% of patients in the combination arm vs 43.5% of those who received FOLFIRINOX alone, and grade 3 or higher AEs attributed to the P-32 device or implantation procedure occurred in 14.6% (n = 6 of 41) of patients in the combination arm. AEs of special interest related to the P-32 microparticles occurred in 22.0% of the combination arm vs 23.9% of the FOLFIRINOX-alone arm. Investigators reported that safety was comparable across arms and that no new safety signals were identified.

Disclosures: Milella reports personal financial interests via advisory board roles with AstraZeneca, MSD, Pfizer, Novartis, Ipsen, Viatris, Janssen, Servier, and Bristol Myers Squibb; an invited speaker role with Bayer; a steering committee role and financial interest with Novartis; institutional funding from Roche; and a steering committee role and personal financial interest with OncoSil Medical.

References

1. Milella M, Malleo G, Garufi C, et al. TRIPP-FFX: an open-label, multi-centre, randomized study of targeted intratumoural placement of phosphorous-32 (OncoSil) in addition to FOLFIRINOX chemotherapy versus FOLFIRINOX chemotherapy alone in patients with unresectable locally advanced pancreatic adenocarcinoma. Presented at: 2026 ESMO Gastrointestinal Cancers Congress; July 1-4, 2026; Munich, Germany. Abstract LBA4.
2. FOLFIRINOX versus OncoSil in addition to FOLFIRINOX in patients with locally advanced pancreatic adenocarcinoma (TRIPP-FFX). ClinicalTrials.gov. Updated February 13, 2026. Accessed July 13, 2026. https://clinicaltrials.gov/study/NCT05466799