Phase 1 trial shows feasibility and safety of neoadjuvant and adjuvant atezolizumab with stereotactic ablative radiotherapy (SABR) for early stage, inoperable non-small cell lung cancer (NSCLC) patients.


SABR is the standard-of-care for medically inoperable, early stage NSCLC, but regional and distant failures remain problematic. Preclinical data have suggested synergy between radiotherapy and checkpoint inhibition, and suggest that neoadjuvant delivery of checkpoint blockade may be superior to adjuvant-only delivery.

In a poster presentation at the virtual meeting of the American Society of Clinical Oncology, researches from the University of California Davis Comprehensive Cancer Center (Sacramento, USA), rereported the results of a phase 1 trial exploring the feasibility and safety of neoadjuvant atezolizumab plus SABR.  Primary endpoint of the trial was to determine the maximum tolerated dose of atezolizumab plus SARB and the recommended phase 2 dose (RP2D).

In total, 20 patients with inoperable, T1-3 NSCLC were enrolled: 15 patients in the dose-finding phase and 5 patients at the recommended phase 2 dose. Patients received 6 cycles of atezolizumab. A 3+3 dose finding design was employed with 3 dose levels: 3 mg/kg, 10 mg/kg, and 1200 mg flat dosing. SABR was delivered starting cycle 3 to 50 Gy over 4-5 fractions. Dose limiting toxicity (DLT) was assessed during the first 9 weeks.

Atezolizumab 1200 mg flat dosing was the RP2D. Grade 3 pneumonitis was not observed. 15/20 patients completed all 6 cycles. Median progression-free survival was 25.5 months.

The researchers concluded  that tezolizumab administrated before, during, and after SABR is feasible, and well tolerated in inoperable early-stage NSCLC. Antitumor activity was observed with 2 doses of atezolizumab. RP2D is 1200 mg. This combination will be tested in a randomized phase 3 trial SWOG/NRG S1914.

 

Kelly K, et al. ASCO 2020 virtual meeting, abstract 9011.