Phase I (safety assessment) of durvalumab (MEDI4736) with focal sensitizing radiotherapy in platinum resistant ovarian, primary peritoneal or fallopian tube epithelial carcinoma.

person Anna Tinker British Columbia Cancer Agency, Vancouver, BC, Canada info_outline Anna Tinker, Peter Lim, Christina Aquino-Parsons, Paul Hoskins, Daniel Khalaf, Stephanie Lheureux, Kathy Han, Mitchell Liu, Julian J Lum

Authors person Anna Tinker British Columbia Cancer Agency, Vancouver, BC, Canada info_outline Anna Tinker, Peter Lim, Christina Aquino-Parsons, Paul Hoskins, Daniel Khalaf, Stephanie Lheureux, Kathy Han, Mitchell Liu, Julian J Lum Organizations British Columbia Cancer Agency, Vancouver, BC, Canada, BC Cancer-Vancouver, Vancouver, BC, Canada, Department of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada, BC Cancer Agency, Vancouver, BC, Canada, British Columbia Cancer Agency-Vancouver Centre, Vancouver, BC, Canada, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada, Princess Margaret Cancer Centre, Toronto, ON, Canada, BC Cancer Vancouver Centre, Vancouver, BC, Canada, Deeley Research Centre, Victoria, BC, Canada Abstract Disclosures Research Funding Pharmaceutical/Biotech Company BC Cancer Foundation Background: Radiation (RT) of malignant neoplasms can induce immunogenic tumor cell death, alter the tumor micro-environment and enhance recruitment of anti-tumor T cells. Co-administration of focal RT and an immune checkpoint-inhibiting agent may overcome immune-suppressive signals and potentiate systemic responses. A phase I study is underway to assess the safety of RT combined with PD-L1 inhibition in patients with recurrent epithelial ovarian/fallopian tube/peritoneal carcinomas (OV). Methods: Women with platinum resistant epithelial OV, ECOG PS 0/1 and ≤ 2 lines of treatment in the platinum-resistant setting are eligible. 1 lesion evaluable by RECIST criteria (v 1.1) and 2 additional lesions suitable for RT (minimal treatment volume 4cc) are required. Pre- and on-treatment biopsies for correlative studies are mandatory. The primary objectives are to assess the safety and tolerability of the focal RT combined with the immune checkpoint inhibitor, durvalumab (D), as defined by dose-limiting toxicities (DLTs), and to define the maximum tolerated RT dose and treatment schedule. The secondary objectives are to evaluate the clinical activity of focal RT and D [RECIST (v 1.1), GCIG CA-125, and immune-related response criteria], progression free survival and overall survival. D 1500 mg delivered intravenously every 28 days = one cycle. RT to the 2 selected target lesions is delivered 24-36 hours prior to the infusion of D. The RT starting dose-level is 24Gy (in 4 fractions) per lesion (given Days -1, 1 and 28 of Cycle 1 and Day 1 of Cycle 2). A 3+3+3 design will permit more extensive exploration of toxicity if DLTs are observed (Table). Investigator assessed DLTs are defined by CTCAE v. 4.03 and include the following: any grade ≥3 adverse event suspected to be related to D or RT (necrosis or recall reactions at previously irradiated sites, RT induced bowel perforation, any unexpected grade 3 or greater toxicity at the site of RT), any grade ≥2 allergic or autoimmune event that involves vital organ function, and any other grade 3 allergic or autoimmune events that do not resolve to grade 1 before the next scheduled dose of D. Treatment may continue up to 12 months. Enrollment began August 2018. To date, no DLTs have been observed at dose level 1 (n= 3) and enrollment is ongoing. Clinical trial information: NCT03283943 Dose Level Durvalumab dose (q 28 days) Total Radiation dose given per target lesion (2 targets per patient) N 1 (starting dose level) 1500 mg 24 Gy/4 fractions 3+3+3 2 1500 mg 32 Gy/4 fractions 3+3+3