Cabozantinib (C) plus atezolizumab (A) or C alone in patients (pts) with advanced non–small cell lung cancer (aNSCLC) previously treated with an immune checkpoint inhibitor (ICI): Results from Cohorts 7 and 20 of the COSMIC-021 study.

Abstract

9005 Background: C, a multitargeted receptor tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment that may enhance ICI activity. COSMIC-021 (NCT03170960) is a multicenter phase 1b study evaluating C + A in advanced solid tumors. In COSMIC-021, C + A demonstrated encouraging clinical activity in the cohort of pts with aNSCLC previously treated with ICIs (cohort 7 [C7]) (Neal. ASCO 2020. Abstr 9610). Updated outcomes of C + A in expanded C7 and outcomes for C alone in exploratory cohort 20 (C20) are presented. Methods: Pts with stage IV nonsquamous NSCLC without mutations in EGFR, ALK, ROS1, or BRAF V600E who progressed on one prior ICI and ≤2 prior lines of systemic anticancer therapy but no prior VEGFR TKI were eligible. Cohorts were not accrued contemporaneously. Pts received C 40 mg PO QD plus A 1200 mg IV Q3W (C7) or C alone 60 mg PO QD (C20). Primary endpoint was objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Results: A total of 81 and 31 pts received C + A and C, respectively; baseline characteristics were as follows: median age, 67 y, 70 y; male, 57%, 58%; ECOG PS 1, 64%, 71%; liver metastasis, 21%, 23%; refractory to prior ICI (progressive disease [PD] as best response), 32%, 45%; median number of prior systemic therapies, 3 and 3. As of Nov 30, 2021, median follow-up (range) (mo) was 24.7 (10.7, 42.8) and 21.5 (17.3, 27.6) for C + A and C, respectively, with 6 (7%) and 1 (3%) on study treatment. Clinical activity was observed for C + A and C alone (Table). Most common treatment-related adverse events (TRAEs) of any grade for C + A and C, respectively, included diarrhea (40%, 42%), nausea (22%, 45%), decreased appetite (25%, 26%), vomiting (14%, 23%), and fatigue (28%, 19%); grade 3/4 TRAEs occurred in 44% and 52% and one grade 5 TRAE occurred in each cohort (pneumonitis [C + A] and gastric ulcer hemorrhage [C]). Conclusions: C + A and C demonstrated encouraging clinical activity with manageable toxicity in pts with aNSCLC previously treated with ICIs. A phase 3 trial (CONTACT-01; NCT04471428) of C + A vs docetaxel is ongoing in NSCLC previously treated with an ICI and platinum-containing chemotherapy. Clinical trial information: NCT03170960. [Table: see text]