VIRAGE: A phase IIb, open-label, randomized study of nab-paclitaxel and gemcitabine plus/minus VCN-01 in patients with metastatic pancreatic cancer.

Abstract

TPS4210 Background: VCN-01 is a modified oncolytic adenovirus type 5 (Ad5) designed to replicate selectively in cancer cells with a dysfunctional RB1-E2F pathway and express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. Results obtained in a previous phase I trial in patients with solid tumors, including metastatic pancreatic cancer, showed that a single systemic administration of VCN-01 is feasible and has an acceptable safety profile alone or when combined with standard of care chemotherapy (SoC) nab-paclitaxel plus gemcitabine (NCT02045602). VCN-01 reached and replicated in tumors and encouraging biological and clinical activity was observed when administered in combination with SoC to patients with metastatic pancreatic adenocarcinoma (mPDAC). Based on the promising phase I results, a phase IIb, open-label, randomized study was initiated to evaluate treatment with two doses of VCN-01 in combination with nab-paclitaxel and gemcitabine in patients with mPDAC. Methods: VIRAGE is a multi-center, open label, randomized, 2-parallel arm, phase IIb trial that evaluates the safety, tolerability and efficacy of two separate VCN-01 intravenous administrations (1x1013 vp/dose) in combination with SoC (nab-paclitaxel at 125mg/m2 and gemcitabine at 1000mg/m2 ) as first line treatment in chemonaïve mPDAC patients. A total of 92 subjects in North America and European Union will be recruited and randomized (1:1) to receive either SoC nab-paclitaxel and gemcitabine (on days 1, 8 and 15 of each 28-day cycle) (Arm I), or doses of VCN-01 administered 1 week prior to SoC nab-paclitaxel and gemcitabine in each of cycle 1 (week 1) and cycle 4 (week 14) (Arm II). Cycles 1 and 4 of Arm II will be 35-day cycles to accommodate VCN-01 dosing, while all other SoC cycles will be 28 days. Patients will continue study treatment until progressive disease (PD), unacceptable toxicity or patient’s/investigator’s decision. The primary endpoint is overall survival (OS) and the assessment of safety and tolerability of two intravenous doses of VCN-01 added to SoC. The secondary objectives include time-to-progression (TTP), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of the response (DoR), 1-year OS and PFS rates, and serial changes in tumor markers (Ca19.9). At 31 Jan 2024, the enrollment is ongoing in US and Spanish sites. Clinical trial information: NCT05673811 .