Final results of a phase I prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or melanoma.

9099 Background: We report final Phase I results of a Phase I/II prospective trial assessing safety and tolerability of SBRT and concurrent pembrolizumab. Methods: Eligible patients had metastatic NSCLC or melanoma and ≥ 2 sites of disease. Patients who had received prior anti-PD1 therapy were eligible if their disease had progressed by RECIST criteria; these patients received SBRT at enrollment. Immunotherapy naïve patients were treated with 200 mg of pembrolizumab q3 weeks until disease progression, then received SBRT. After SBRT, patients received pembrolizumab q3 weeks until disease progression. Patients were assigned to an SBRT dose escalation arm based on target location: either in the lung (arm A) or elsewhere (arm B). Results: 24 patients were enrolled (melanoma n=5; NSCLC n=19). 9 patients had received prior anti-PD-1 therapy and therefore got SBRT at enrollment. 15 patients were immunotherapy naïve and received a mean of 8.3 cycles of pembrolizumab before disease progression and SBRT. The target SBRT dose of 30 Gy in 3 fractions was reached for each arm. No dose limiting toxicities (DLTs) were observed within 60 days of SBRT. Non-hematologic toxicities of > grade 2 occurring during the 60 day DLT window or during subsequent pembrolizumab treatment are presented in the table below, with immune-related adverse events noted. 5 of 24 patients (21%) had an immune mediated grade 2 or 3 adverse event during post SBRT immunotherapy. Patients received pembrolizumab for a mean of 19.8 weeks post-SBRT (range 0-52 weeks) before disease progression. Conclusions: Dose escalation to 30 Gy in 3 fractions was completed for both arms without dose limiting toxicity. Combination therapy was well tolerated. Preliminary efficacy data indicates that addition of SBRT to a single site resulted in a mean of 19.8 weeks of continued response. Clinical trial information: NCT02407171. Pre SBRT Arm A (Lung Target) Arm B (Non Lung Target) 30 Gy in 5 fx 30 Gy in 3 fx 30 Gy in 5 fx 30 Gy in 3 fx n 15 7 6 4 7 Gr 2 4 hypothyroid; n=1pneumonitis; n=1 2 2 colitis; n=1 0 3 pneumonitis; n=1 Gr 3 1 hypothyroid; n=1 1 pneumonitis; n=1 2 enterocolitis; n=1pneumonitis; n=1 0 1 colitis; n=1 Gr 4 0 0 0 0 0 Gr 5 0 0 0 0 0