Niewiarowska, Anna A.

723 Background: BPM31510-IV is an Ubidecarenone (CoQ10) drug-lipid conjugate nanodispersion targeting metabolic machinery in cancer, shifting bioenergetics from lactate dependency towards mitochondrial OxPhos to generate ROS and activate apoptosis. An MTD of BPM31510-IV in combination with gemcitabine was established at 110mg/kg in a Phase I clinical trial, which determined the dose for the Phase 2 investigation. Methods: Eligible patients (aged ≥ 18 y) with relapsed/refractory PDAC to standard treatment (ST) and met inclusion/exclusion criteria were recruited. Patients received 110mg/kg IV BPM31510 in combination with gemcitabine in a 144-hour infusion. Tumor response was evaluated at week 10 and then every 8 weeks. Study endpoints assessed were Overall Response Rate (ORR), Overall Survival (OS), Progression-Free Survival (PFS), Time to Progression (TTP), Tumor Response using Adaptive Molecular Responses (multi-omic molecular profiling), changes in CA 19-9 levels and patient reported Quality of Life (QOL) using the validated FACT-HEP PRO. A comprehensive multi-omic profiling for identification of biomarkers for patient stratification was explored. Results: Of the 35 patients enrolled to receive therapy, 18 patients met criteria of an adequately treated cohort (ATC- received BPM31510-IV + gemcitabine for 30 days over 2 cycles and had a RECIST 1.1 evaluation) while remaining (n = 17) had progressive disease (PD). Half of the ATC population (n = 9/18, 50%) achieved best ORR of stable disease (SD); 10/18 (55 %) demonstrated SD as best response at target lesions and 8/18 demonstrated SD at end of Cycle 2. The mTTP was 121 days (70 – 147, 95% CI); PFS 118 days (70 – 131, 95% CI) and OS 218 days (131 – 228, 95% CI), respectively. Overall, BPM31510-IV was well tolerated; the most common AE’s were GI related. Conclusions: The efficacy signal observed in this heavily pretreated population in addition to the toxicity profile warrants further clinical investigation of BPM31510-IV + gemcitabine in advanced PDAC. Clinical trial information: NCT02650804 . [Table: see text]

341 Background: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity to DNA damaging agents such as the platinums. Cisplatin was added to a nab-paclitaxel + gemcitabine regimen, which has been determined to improve survival over gemcitabine alone (NEJM 2013; 369:1691-1703). The objectives are to determine the efficacy and safety of nab-paclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer. Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Doses are nab-paclitaxel 125 mg/m2 undiluted, gemcitabine 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes on days 1 and 8 of a 21 day cycle, along with 3 different dose levels of cisplatin (25, 37.5 or 50 mg/m2) in 500 ml of NS infused over 60 minutes, after the nab-paclitaxel infusion. Pre and post cisplatin hydration was given. The maximum tolerated dose and phase II dose of cisplatin is 25 mg/m2. Results: 25 pts were treated; 24 were evaluable (baseline and ≥ 1 follow up CT scan). The most common drug related grade (gr) 3 - 4 adverse events (AEs), n = 25, were thrombocytopenia 76% (gr 3 = 36%, gr 4 = 40%) with no serious bleeding events, anemia 32% (gr 3 = 32%, gr 4 = 0%), neutropenia 24% (gr 3 = 20%, gr 4 = 4%), infection 20% (gr 3 = 16%, gr 4 = 4%), and diarrhea 16% (gr 3 = 16%, gr 4 = 0%). Peripheral neuropathy ≥ gr 3 was seen in only 1 pt (gr 3 = 4%). Grade 5 AEs were infection (1), cardiac arrest (1), and stroke (1). Median time on therapy was 5.5 months, range (1 – 9.5). By RECIST 1.1 criteria, 2 pts had complete response (8.3%), 15 partial response (62.5%), 4 stable disease (16.7%), and 3 progressive disease (12.5%). Median overall survival to date as of 11/10/16 is 16.5 months. Conclusions: Although a small study, the high response rate and landmark evolving median survival are very encouraging. This regimen is being expanded in patients with stage IV pancreatic cancer, neoadjuvant and adjuvant settings. Clinical trial information: NCT01893801.