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 (leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) 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, the LDCRs at 16 weeks by blinded independent central review were 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 LDCRs were 85.0% (95% CI, 70.2%-94.3%) vs 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 adult patients with histologically or cytologically confirmed, unresectable, locally advanced pancreatic adenocarcinoma (per National Comprehensive Cancer Network 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 receive FOLFIRINOX alone or FOLFIRINOX plus P-32 microparticles, stratified by FOLFIRINOX or modified FOLFIRINOX regimen and by KPS (100-90 vs 80-70).¹ Patients received up to 12 cycles of FOLFIRINOX, with continuation at investigator discretion; those in the combination arm underwent planned P-32 microparticle implantation in 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 United Kingdom.

Of 119 patients screened, 31 did not pass screening, and 88 were randomly assigned to the ITT population.¹ Protocol deviations occurred in 2 patients in the FOLFIRINOX arm and 5 patients in the combination arm.

Baseline characteristics were broadly similar between the investigational and control arms, respectively, including median age (63.0 years [range, 41-81] vs 65.0 years [range, 42-79]), median longest diameter of target tumor (35.5 mm [range, 15.3-72] vs 36.3 mm [range 14.8-69]), and median target tumor volume (12 cc [range, 1-41] vs 13 cc [range, 1-58]). Patients in these respective arms received a median of 11 (range, 0-25) vs 12 (range, 1-22) cycles of FOLFIRINOX, with cumulative multiagent relative dose intensities of 75.9% vs 67.9%. All evaluable patients in the combination arm received P-32 microparticle implantation to the target tumor.

What were the additional efficacy data from the TRIPP-FFX trial?

Secondary efficacy end points numerically favored the P-32 microparticles combination vs control in the ITT population, including objective response rate (55.6% vs 37.2%), median local progression-free survival (PFS; 12.8 months [95% CI, 7.8-not calculable (NC)] vs 11.8 months [95% CI, 7.8-NC]), median PFS (12.1 months [95% CI, 7.8-15.1] vs 9.9 months [95% CI, 7.8-NC]), and median overall survival (OS; 18.2 months [95% CI, 13.8-NC] vs 15.8 months [95% CI, 10.2-NC]). Surgical resection was performed in 11.1% vs 11.6% of patients, respectively, with R0 margins achieved in 60% vs 16.7% of resected patients. The median rate of maximal tumor volume decrease was −72.1% with the combination vs −57.0% with FOLFIRINOX alone.

What did the safety analysis of TRIPP-FFX show?

Any-grade adverse effects (AEs) occurred in 97.8% of patients treated with FOLFIRINOX alone (n = 46) and 100% of those who received the P-32 microparticles combination (n = 41); 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 transaminase levels (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% of patients in the combination arm. AEs of special interest related to the P-32 microparticles occurred in 22.0% of patients in the combination arm vs 23.9% of those in the FOLFIRINOX-alone arm. The investigators reported that safety data were comparable between the arms and that no new safety signals were identified.

References

1. Milella M, Wasan HS, Eccles A, et al. TRIPP-FFX: An open-label, multi-centre, randomized study of TaRgeted Intratumoural placement of phosphorous-32 microparticles added to FOLFIRINOX (FFX) versus FFX alone in patients with unresectable locally advanced pancreatic cancer (uLAPC). Ann Oncol. 2026;37(suppl 1):S121. doi: 10.1016/j.annonc.2026.06.011
2. FOLFIRINOX versus OncoSil in addition to FOLFIRINOX in patients with locally advanced pancreatic adenocarcinoma (TRIPP-FFX). ClinicalTrials.gov. Updated February 13, 2026. Accessed September 24, 2026. https://clinicaltrials.gov/study/NCT05466799