Novartis announces Tabrecta first published overall survival and updated overall response data in patients with METex14 metastatic NSCLC.

Data from the ongoing, pivotal, multi-cohort Phase II GEOMETRY mono-1 study was presented during the 2021 Annual American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting (Poster Discussion Session, Lung Cancer—Non-Small Cell Metastatic; June 4, 2021, 9:00 AM-10:00 AM CT; abstract 9020). The analysis includes new data from the treatment-naïve (1L) expansion cohort 7 and previously-treated (2L+) cohort 6, and mature data from previously-reported cohorts, for a total of 160 patients. The results presented provide additional data on the efficacy of Tabrecta in both treatment-naïve and previously-treated patients with METex14 metastatic NSCLC 2: i.• Overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1: . o 67.9% (95% CI: 47.6, 84.1) and 65.6% (95% CI: 46.8, 81.4) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively). o 40.6% (95% CI: 28.9, 53.1) and 51.6% (95% CI: 33.1, 69.8) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively) . ii• Median duration of response (DOR) based on BIRC assessment: o 12.6 months (95% Cl: 5.6 NE) and NE (95% CI: 5.5-NE) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively).o 9.7 months (95% Cl: 5.6 13.0) and 8.4 months (95% Cl: 4.2 NE) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively). iii. • Overall survival (OS) : o 20.8 months (95% CI: 12.42, NE [not estimated]) among treatment-naïve patients (Cohort 5b; n= 28). o 13.6 months (95% CI: 8.61, 22.24) among previously-treated patients (Cohort 4; n= 69). o Median OS for expansion Cohorts 6 & 7 are not reached. No new safety signals or unexpected safety findings were observed . Ninety-eight percent of subjects had at least one adverse event (AE) of any grade and 50.9% of subjects had at least one serious adverse event (SAE). Thirteen percent were suspected to be treatment-related. The most common adverse events ( greater than 20%, all grades) across all cohorts were peripheral edema, nausea, vomiting, increased blood creatinine, dyspnea, fatigue and decreased appetite. The majority of AEs were grade 3 or 42. Currently, the five-year survival rate for lung cancer is less than 20% , decreasing further when the disease is diagnosed at later stages. Nearly one in three patients with metastatic NSCLC may have an actionable mutation. METex14 has been reported to occur in 3%-4% of metastatic NSCLC cases. Many patients with mutations that lead to METex14 are not diagnosed with NSCLC until their disease has progressed to later stages and often have poor prognosis. A separate analysis of patient-reported outcomes (PROs) evaluated cough, delayed time to lung symptom deterioration, and quality of life (QoL) in NSCLC patients with METex14 (abstract 9056). • Median time to definitive deterioration (TTDD)in global health status (GHS) was 16.6 months (95% CI: 9.7, NE) and 12.4 months (95% CI: 4.2, 19.4) in 1L and 2L+ patients, respectively. • Median TTDD for cough and chest pain was NE in both 1L and 2L+ patients, and for dyspnea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE), respectively. • An exploratory post hoc analysis evaluated QLQ-LC13 symptoms (cough, chest pain, and dyspnea) over time for patients achieving a clinical response, as assessed by BIRC, found these symptoms improved at all cycles in patients achieving clinical complete response (CR) or partial response, while symptom worsening was seen in those with no clinical response Additionally, a retrospective analysis of GEOMETRY mono-1 validates the clinical utility of liquid biopsy testing to identify METex14 positive patients for treatment with Tabrecta (Poster Session: Lung Cancer—Non-Small Cell Metastatic; abstract 9111). About GEOMETRY mono-1: GEOMETRY mono-1 is a Phase II a multi-center, non-randomized, open-label, multi-cohort study in adult patients with EGFR wild-type, ALK-negative rearrangement, metastatic NSCLC harboring mutations that lead to MET exon-14 skipping who received capmatinib tablets 400 mg orally twice daily. Patients were assigned to cohorts on the basis of MET status and previous lines of therapy. The primary endpoint was overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) evaluated by BIRC. See- Wolf, J. et.al. "Capmatinib in MET exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study". Abstract #9020. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL. See- Wolf, J. et.al. "Patient-reported outcomes in capmatinib-treated patients with METex14- mutated advanced NSCLC: Results from the phase II GEOMETRY mono-1 study". Abstract #9056. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.