Abstract PO-051: PANOVA-3: A phase III study of tumor treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma

Abstract

Abstract Tumor Treating Fields (TTFields) are a non-invasive, loco-regional antimitotic treatment modality, approved for the treatment of glioblastoma and malignant pleural mesothelioma. TTFields at a specific frequency (150-200 kHz) are delivered via arrays placed on the skin surrounding the tumor site. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase 2 PANOVA study, the first trial testing TTFields in pancreatic cancer patients, demonstrated the safety and preliminary efficacy of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and locally advanced pancreatic adenocarcinoma (LAPC). The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy and safety of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on day 1, 8, and 15 of a 28 day cycle. The protocol has recently been amended to incorporate the use of a smaller, lighter (weight reduced from 6 to 2.7 lbs.) TTFields device. TTFields (150 kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q4w, including a CT scan of the chest and abdomen q8w. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint. Progression-free survival, objective response rate, rate of resectability, quality of life, and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Citation Format: Vincent J. Picozzi, Teresa Macarulla, Philip A. Philip, Carlos R. Becerra, Tomislav Dragovich. PANOVA-3: A phase III study of tumor treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-051.