LAUSR

Background: Capmatinib is a highly selective and potent MET inhibitor that crosses the blood-brain barrier. In the GEOMETRY mono-1 study, capmatinib showed clinically meaningful response rates in pts with advanced NSCLC harboring METex14 skipping mutations, including activity in pts with baseline BM, and also demonstrated manageable safety. Here, we present efficacy and safety data, including an efficacy analysis in METex14 skipping mutated NSCLC pts with baseline BM. Methods: The phase 2, multi-cohort, multicenter GEOMETRY mono-1 study (NCT02414139) is evaluating capmatinib in adult pts with ECOG PS 0-1, ALK and EGFR-wt, METex14-mut/MET-amplified stage IIIB/IV NSCLC, including pts with neurologically stable/asymptomatic BM. Pts were assigned to Cohorts 4 (pretreated, 2/3L) and 5b (treatment-naive) and received capmatinib 400 mg BID. Primary endpoint: overall response rate (ORR) by BIRC per RECIST v1.1. Key secondary endpoint: duration of response (DOR) by BIRC. The retrospective analyses on brain lesions were based on modified RECIST v1.1 as assessed by BIRC neuro-radiologic assessments of all Cohorts 4 and 5b pts with baseline BM. Results: As of April 15, 2019, 97 pts (Cohort 4: 69 pts; Cohort 5b: 28 pts) were evaluable for efficacy. BIRC results for cohorts 4 and 5b, respectively, were (i) ORR (95%CI): 40.6% (28.9-53.1) and 67.9% (47.6-84.1), (ii) median DOR (95%CI): 9.72 (5.55-12.98) and 11.14 (5.55-NE) months (mos), and (iii) median progression-free survival (95%CI): 5.42 (4.17-6.97) and 9.69 (5.52-13.86) mos. There were 13 pts with evaluable baseline BM by BIRC [3.3 brain lesions/pt (range 1−8)]. 7 of the 13 pts (54%) had intracranial response of which 4 pts had complete resolution of all brain lesions. The other 3 responders had (i) complete resolution in 3 lesions, −50% reduction in 1 lesion, stabilization in remaining 4 lesions (total 7 lesions), (ii) complete resolution in 2 lesions, stabilization in 1 remaining lesion (total 3 lesions), and (iii) complete resolution in 1 lesion, stabilization in 3 remaining lesions (total 4 lesions). Intracranial disease control was achieved in 12/13 pts. Intracranial responses were as fast as systemic responses. 3/7 responders had prior brain radiotherapy; 5/7 responders had either signs of progression in the existing brain lesion(s) or new BM at study entry. Most common tx-related adverse events (≥15%, all grades) across all cohorts (N=334) were peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%). Conclusion: BIRC neuro-radiologist review of 13 pts with evaluable baseline BM suggested that capmatinib has anti-tumor efficacy in the brain. Capmatinib also showed deep and durable responses in pts with METex14-mut advanced NSCLC regardless of line of therapy and demonstrated a manageable safety profile. Citation Format: Edward B. Garon, Rebecca S. Heist, Takashi Seto, Ji-Youn Han, Noemi Reguart, Harry J. Groen, Daniel SW Tan, Toyoaki Hida, Maja J. de Jonge, Sergey V. Orlov, Egbert F. Smit, Pierre-Jean Souquet, Johan Vansteenkiste, Sylvie Le Mouhaer, Anna Robeva, Maeve Waldron-Lynch, Monica Giovannini, Juergen Wolf. Capmatinib in METex14-mutated (mut) advanced non-small cell lung cancer (NSCLC): Results from the phase II GEOMETRY mono-1 study, including efficacy in patients (pts) with brain metastases (BM) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT082.