Abstract B36: Compassionate use of an oncolytic adenovirus in a Stage IV treatment-refractory ovarian cancer patient

Ovarian cancer remains the most common cause of death due to gynecologic cancers, and due to its ambiguous symptomatology, diagnosis often occurs at late stages, and prognosis is poor. This case report describes the compassionate use of an oncolytic adenovirus, ONCOS-102, in a 46-year-old female with Stage IV treatment-refractory serous ovarian cancer presenting with metastases to the groin and left breast, peritoneal carcinomatosis, and pleural carcinomatosis. The patient was initially diagnosed in 2007 with a low-grade serous adenocarcinoma of the ovary (pT3, pN1, pMx, G1), c-kit-positive, ER-positive, HER2/EGFR-negative, BRAF -negative and KRAS mutation-negative. Since then, the patient had received multimodal chemotherapy followed by multiple courses of maintenance therapy, with treatments including Bevacizumab (Avastin), Diflunisal/ASA, PAS/ASA, Abraxane, Tamoxifen, Alimta, Gemcitabine, and Topotecan. The patient had also received abandoned radiotherapy and dendritic cell vaccine immunization. Oncos Therapeutics provided ONCOS-102 for compassionate use, based on the rationale that there was no satisfactory alternative treatment, and she was unable to obtain the drug under another IND or clinical trial protocol. ONCOS-102 (Ad5/3-D24-GMCSF) is an oncolytic adenovirus that, due to a 24-bp deletion in its E1A gene, selectively replicates in cancer cells with a defective Rb pathway, and its Ad5 fiber knob protein is replaced with that of Ad3 to facilitate entry into tumor cells. In addition, the virus is armed with a transgene encoding granulocyte/macrophage colony-stimulating factor (GM-CSF). Thus, ONCOS-102 is hypothesized to mediate therapeutic benefit through multiple mechanisms, including direct oncolysis of tumor cells, triggering necrosis/apoptosis via vascular disruption, and activation of innate and adaptive immunity, leading to the induction of a systemic anti-tumor response. Thus, oncolytic virotherapy can be viewed as a form of in situ vaccination, and to further potentiate its effects, our single-patient compassionate use protocol further incorporated a low priming dose of cyclophosphamide (250 mg/m2 IV bolus) for Treg depletion, and a dual checkpoint inhibitor treatment regimen with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Approval for the use of this protocol in this patient was obtained from the FDA, as well as the University of Miami9s local Institutional Review Board (IRB) and Institutional Biosafety Committee (IBC). The patient passed pre-treatment evaluations and informed consent was obtained for administration of the virus, which was performed following the cyclophosphamide “priming” regimen at a virus dose of 3 x 10^11 VP by intralesional injection into accessible tumors. No product-related adverse events have been observed, and further clinical results will be presented. Citation Format: Katharina Feister, Sara Collins, Noriyuki Kasahara, Brian Slomovitz. Compassionate use of an oncolytic adenovirus in a Stage IV treatment-refractory ovarian cancer patient. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B36.