The Phase III Study: Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for locally advanced pancreatic cancer (TIGeR-PaC)

Treatment of locally advanced pancreatic cancer (LAPC) remains a clinical challenge, with a median survival of 16-18 months. Local disease control measures, coupled with systemic therapy, is a treatment paradigm being investigated in this disease. Double-balloon mediated local intra-arterial gemcitabine (IAG) delivery to the tumor has demonstrated safety in patients with LAPC. TIGeR-PaC is an ongoing Phase III clinical trial comparing the efficacy of IAG to the standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC.

The trial includes an induction phase of upfront systemic chemotherapy and radiation. ECOG 0-1 LAPC subjects receive 3 cycles of GN and 1 cycle of radiation (SBRT, 33 Gy in 5 fractions). Following induction, patients with non-progressive disease are randomized to IAG (8 treatments bi-weekly for 16 weeks) or IV GN for 4 cycles over 16 weeks. After the randomized therapy, patients with non-progressive disease receive continuation IV GN or low-dose oral capecitabine, per investigator’s preference, until disease progression and are followed for survival. The primary endpoint is overall survival (OS). The hazard functions are assumed to be proportional during the randomized treatment period. The two functions become approximately identical during the continuation treatment period. The first interim analysis for the ITT population was performed after the 26th of the expected 86 events. The trial's secondary endpoints include PFS, tolerability (including AEs), use of colony-stimulating factor for neutropenia, and quality of life.

The first interim analysis occurred after the 26th event in the trial; at the time, 45 patients had been randomized, 23 to IAG and 22 to IV GN, and the survival status of all subjects was used. There was an equal number of primary events, 13, in each arm. The median OS in the IV GN arm was 10 months vs. 16 months in the IAG arm. The p-value, based on Wilcoxson's non-proportional hazard ratio, was 0.08. The PFS in the IV GN arm was 7 months vs. 15 months with IAG (HR 0.55; CI: 0.21-1.47). There was a 3-fold increase in AEs in the IV GN arm vs. the IAG arm (245 vs. 85); most of the difference in AEs were hematological (neutropenia and thrombocytopenia); 15% of patients in the IV GN arm received colony-stimulating factor vs. 0% in the IAG arm. Lastly, regarding the tolerability of completing all 4 cycles of active treatment without treatment modification, 61% of patients in the IAG arm completed all intended treatments vs. 23% of the patients in the IV GN arm. Quality of life assessments are still pending.

The first interim analysis of the study shows favorable results for IAG therapy compared to IV GN. The study continues to accrue patients with a second interim analysis after 52 events expected at the end of 2024.

NCT 03257033.

RenovoRx.

M. Pishvaian: Advisory / Consultancy: Astra Zeneca, Merck, Ideaya, Seattle Genetics, Merus; Research grant / Funding (institution): Seattle Genetics, Tesaro, Arcus Bio, Ideaya, Repare Tx, Novartis, Pfizer, Merck, Tizonia, Biomed Valley Discovories, Amgen, RenovoRx, Boerhinger Ingelheim, Astellas, Hutchinson Medipharma, Takeda, AstraZeneca, Exelixis, Caris, Incyte, Ipsen, Natera, Bayer, BMS, EISAI, Foundation Medicine, Pfizer, SeaGen, Taiho, Tempus, Merck, AstraZeneca, SeaGen, Exelixis, Pfizer, Novartis; Travel / Accommodation / Expenses: Astellas; Shareholder / Stockholder / Stock options: Perthera, Inc.; Licensing / Royalties: Perthera, Inc - Patent, Abbvie - Patent pending. C. Laing: Advisory / Consultancy: Boston Scientific. R. Agah: Shareholder / Stockholder / Stock options: Renovorx; Full / Part-time employment: Renovorx. K. Goodman: Advisory / Consultancy: RenovoRx. All other authors have declared no conflicts of interest.