Final Results of a Phase I Prospective Trial Evaluating the Combination of Stereotactic Body Radiation Therapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma

Abstract

Synergy between immune checkpoint inhibition and radiation therapy enhances antitumoral immunity in preclinical models. We report the final results of the Phase I portion of a Phase I/II prospective trial designed to assess the safety and tolerability of SBRT delivered with concurrent pembrolizumab. Eligible patients had metastatic NSCLC or melanoma and ≥2 measurable sites of disease. Patients who had received prior anti-PD1 immunotherapy 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 coming off study for 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). Twenty-four patients enrolled in the Phase I portion of the study (melanoma n=5; NSCLC n=19). 9 patients had received prior anti-PD-1 therapy and therefore got SBRT at enrollment. Fifteen 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 post-SBRT. Non-hematologic toxicities of grade 2 or higher 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 continued to receive pembrolizumab for a mean of 19.8 weeks post-SBRT (range: 0-52 weeks) before disease progression. We completed escalation to the planned dose of 30 Gy in 3 fractions for both arms without observing dose-limiting toxicity. Combination therapy was well tolerated. Preliminary efficacy data indicates that the addition of SBRT to a single site of disease resulted in a mean of 19.8 weeks of continued response. The phase II portion of the study continues enrollment; progress to date regarding efficacy as well as correlative studies of T cell responses in the peripheral blood will be presented.Abstract 34; TablePre SBRTArm A (Lung Target)Arm B (Non-Lung Target)30 Gy in 5 fx30 Gy in 3 fx30 Gy in 5 fx30 Gy in 3 fxn157647Gr 24 hypothyroid; n=1pneumonitis; n=122 colitis; n=103 pneumonitis; n=1Gr 31 hypothyroid; n=11 pneumonitis; n=12 enterocolitis; n=1pneumonitis; n=101 colitis; n=1Gr 400000Gr 500000 Open table in a new tab