Toca 6: A phase 1b study of Toca 511 and Toca FC in patients with advanced solid tumors or lymphoma.
Presented Monday, June 4, 2018
Authors:
Jaime R. Merchan, Jordi Rodon Ahnert, Gerald Falchook, Derek Ostertag, Dalissa Tejera, Harry E. Gruber, Douglas J. Jolly, Jolene Shorr; University of Miami, Miami, FL; Vall d'Hebron University Hospital, Barcelona, Spain; Sarah Cannon Research Institute at HealthONE, Denver, CO; Tocagen, Inc., San Diego, CA; Sylvester Comprehensive Cancer Center, Miami, FL, US
Background:
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector that selectively infects cancer cells. Toca 511 spreads through tumors, stably delivering an optimized cytosine deaminase (CD) gene that converts the prodrug, Toca FC (investigational, extended-release 5-FC), into 5-FU within the tumor microenvironment. Preclinical studies show 5-FU kills infected dividing cancer cells and diffuses and kills surrounding cancer cells, myeloid derived suppressor cells, and tumor associated macrophages, thus reestablishing tumor immunity. A prior clinical study showed CD protein expression in resected high grade glioma tumors after intravenous (IV) Toca 511 (1Cloughesy T, Walbert T, Bota D, et al. Neuro Oncol 2016; 18(suppl 6):vi17). In animal models of metastatic colorectal cancer, IV Toca 511 infected metastases; subsequent 5-FC treatment resulted in decreased tumor size, improved survival, and durable antitumor immunity (2Yagiz K, Rodriguez-Aguirre ME, Espinoza FL, et al. Molecular Therapy: Oncolytics. 2018; 8:14-26).
Methods:
Toca 6 is a Phase 1b, multicenter, open-label study (NCT02576665) investigating changes in immune activity after treatment with Toca 511 & Toca FC in patients with advanced solid tumors or lymphoma. Toca 511 is injected IV daily for 3 days, then intratumorally following biopsy or, for patients with brain metastases, into resection cavity walls following resection. Oral Toca FC is started ~4 weeks later and repeated every 4-6 weeks. Changes from baseline in intratumoral immune activity (infiltrating T-cell subpopulations, B cells, monocytes) at 4 weeks after start of Toca FC are assessed. Peripheral blood is analyzed for effector, memory, Treg, and myeloid lineage cells. Viral RNA, DNA, and CD protein expression in tumor after IV Toca 511 are measured. Safety and efficacy are assessed. Approximately 30 patients will be enrolled at 4 sites in the United States. Enrollment progress by tumor type will be provided at the time of the meeting. Clinical trial information: NCT02576665
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