Cabozantinib in combination with atezolizumab in non-small cell lung cancer (NSCLC) patients previously treated with an immune checkpoint inhibitor: Results from cohort 7 of the COSMIC-021 study.

Abstract

9610 Background: First-line immunotherapy with/without chemotherapy is standard of care for patients (pts) with advanced NSCLC; however, there is a need for effective treatment options after progression on a prior immune checkpoint inhibitor (ICI). Cabozantinib (C) may augment response to ICI by inhibiting kinases implicated in suppressing immune cell responses and has shown encouraging clinical activity in combination with ICI in other tumor types including RCC and HCC. COSMIC-021, a multicenter phase 1b study, is evaluating the combination of C with atezolizumab (A) in various solid tumors (NCT03170960). We report results from cohort 7 in NSCLC pts after prior ICI therapy. Methods: Eligible pts had ECOG performance status (PS) 0-1 and radiographic progression after one prior anti-PD-1/PD-L1 ICI given alone or in combination with chemotherapy for metastatic non-squamous NSCLC. Up to 2 lines of prior systemic anticancer therapies were permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Primary endpoint is ORR per RECIST 1.1 by investigator. Other endpoints include safety, duration of response (DOR), progression-free survival, and overall survival. Results: Thirty pts with advanced NSCLC were enrolled. Median age was 67 yrs (range 41, 81), 43% were male, 57% had ECOG PS 1, and 23% had liver metastases. Median duration of prior ICI therapy was 4.8 months (mo; range 0.8, 29), and 15 (50%) pts were refractory to prior ICI (progressive disease as best response). As of December 20, 2019, the median follow-up was 8.9 mo (range 5, 20) with 9 (30%) pts continuing study treatment. The most common treatment related adverse events (TRAEs) of any grade were diarrhea (53%), fatigue (37%), nausea (23%), decreased appetite (20%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%). Grade 3/4 TRAEs occurred in 14 (47%) pts, and 1 (3.3%) had grade 5 TRAEs of myocarditis and pneumonitis. Confirmed ORR per RECIST 1.1 was 23% (7 of 30 pts; all partial responses including 3 pts refractory to prior ICI). Time to response was 1.4 mo (range 1, 3), and median DOR was 5.6 mo (range 2.6, 6.9). DCR (CR+PR+SD) was 83%. Conclusions: The combination of C and A had an acceptable safety profile and showed encouraging clinical activity in pts with advanced NSCLC who had progressed after prior ICI therapy. The response rate was greater than previously observed with C monotherapy. Due to the promising data, enrollment in this cohort has been expanded and is ongoing. Clinical trial information: NCT03170960 .