Expansion Cohort Of Partially Irradiated Tumors On A Phase 1 Trial Of Pembrolizumab And Ablative Radiotherapy.

TPS3122 Background: Preclinical studies suggest multi-organ site ablative radiation therapy (MOSART) may enhance systemic anti-tumor response through altering the balance of innate and adaptive immunity within the tumor microenvironment and through direct tumor debulking. Previously, we opened a phase I study to evaluate the safety and efficacy of the combination of pembrolizumab with MOSART for patients with metastatic solid tumors. In the first cohort of 73 patients analyzed, the combined therapies were safe in all organ systems studied with no radiation dose reductions (Luke & Lemons et al. J Clin Oncol 2018, in press). Interestingly, large partially irradiated tumors exhibited control similar to smaller completely irradiated tumors (93% vs. 96% at 6 months, p = 0.32). In December 2017, we opened an expansion cohort to formally test the secondary hypothesis that partially irradiated tumors exhibit local control similar to completely irradiated tumors when combined with immunotherapy. Methods: We are accruing patients with metastatic disease progressing on standard of care treatment, two or more lesions amenable to MOSART, and have at least one lesion greater than 65cc. Enrollment is currently at six of forty planned subjects, and is actively accruing patients. MOSART dosing is based on NRG BR-001 (30 Gy in 3 fractions for osseous and spinal lesions; 45 Gy in 3 fractions for peripheral lung, liver, and abdominal-pelvic lesions; 50 Gy in 5 fractions for central lung, mediastinal, and cervical lesions). At least two lesions are targeted for each patient and not all sites of disease are treated. The maximum gross tumor volume (GTV) that is completely irradiated is 65cc. Partial tumor irradiation is administered to lesions > 65cc where the target volume is created by performing volume contraction down to 65 cc within the initial radiographically defined GTV. Pembrolizumab 200mg IV Q3W is to be initiated within seven days after final MOSART treatment. RECIST 1.1 will be used used to assess radiated tumor progression. Control (defined as CR, PR, or SD) will be calculated by the Kaplan Meier method and compared between partially irradiated tumors and completely irradiated tumors with the log-rank test. Clinical trial information: NCT02608385.