Brief Report: A Phase I Trial of Atezolizumab and Varlilumab in Combination with Radiation in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC)

Introduction Anti-PD(L)1 immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT). Methods We conducted an open-label, single-center, Phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior PD(L)1 therapy. On Day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2. Results 15 patients were enrolled (1 patient did not start treatment). Median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (TRAE); 7 (50%) had at least one grade 3 or worse TRAE. There was only one grade 3 immune-related AE requiring steroids (1 diarrhea/colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, 3 patients had stable disease (SD; 2 with SD > 4 months) and clinical benefit rate was 25%. Median PFS was 2.0 months and median OS was 6.4 months. Conclusions Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.