Abstract 1256P
Background
Capmatinib showed clinically meaningful efficacy in patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14) in GEOMETRY mono-1, a phase II, multi-cohort, multicenter trial evaluating capmatinib 400 mg BID in MET dysregulated stage IIIB/IV NSCLC. Here, we present updated safety from this study (data cut-off: 18-Sep- 2020), including all pts with MET dysregulated NSCLC.
Methods
The median time to first occurrence is reported using descriptive statistics; median time to resolution is calculated using the Kaplan-Meier method. At the data cut-off date.
Results
373 pts with MET dysregulation were enrolled; this included 29 pts with METex14 mutation who had brain metastasis (BM) at baseline and neurological BIRC review. Treatment-related (TR) AEs were reported in 86.9% of pts in the safety population and 89.7% of those with BM at baseline. The most common TRAEs for the safety population and pts with BM at baseline are reported in the table. Similar AEs were observed in pts with BM and the safety population; no nervous system disorders were reported in pts with BM. For the most frequent TRAEs in the safety population, peripheral edema and nausea, the median (min-max) time to first occurrence of any grade of symptoms was 2.04 (0.03‒24.84; n=178) and 0.39 (0.03‒21.42, n=128) months, respectively; the median (min‒max) time to first occurrence of grade 3 or 4 symptoms was 5.04 (0.03‒31.80; n=34) and 0.54 (0.20‒1.48; n=6) months, respectively. The median (95% CI) time to resolution of first grade 3 or 4 symptoms (recovered/resolved or return to grade ≤ 2) of TR peripheral edema and nausea was 0.49 (0.33, 0.92) and 0.18 (0.10, NE) months, respectively. TR peripheral edema and nausea led to a dose adjustment in 9.7% and 1.9% pts, dose interruption in 10.5% and 5.4% pts and to permanent discontinuation in 2.1% and 0.5% of pts, respectively. Table: 1256P
Most common TRAEs (≥10% in the safety population)
| All patients N=373 | Pts with METex14 and brain metastasis N=29 | |||
| All grades n (%) | Grade 3/4 n (%) | All grades n (%) | Grade 3/4 n (%) | |
| Any TR AE | 324 (86.9) | 147 (39.4) | 26 (89.7) | 14 (48.3) |
| Peripheral edemaa | 178 (47.7)[LMS1] | 34 (9.1) | 14 (48.3) | 4 (13.8) |
| Nausea | 128 (34.3) | 6 (1.6) | 15 (51.7) | 1 (3.4) |
| Increased blood creatinine | 74 (19.8) | 0 | 2 (6.9) | 0 |
| Vomiting | 71 (19.0) | 7 (1.9) | 8 (27.6) | 0 |
| Fatigue | 51 (13.7) | 10 (2.7) | 4 (13.8) | 2 (6.9) |
| Decreased appetite | 47 (12.6) | 3 (0.8) | 4 (13.8) | 0 |
| Diarrhea | 40 (10.7) | 1 (0.3) | 0 | 0 |
aPeripheal edema includes peripheral swelling, peripheral edema and fluid overload.
Conclusions
Overall, capmatinib demonstrated a manageable safety profile, with no new safety signals in pts with MET dysregulated NSCLC.
Clinical trial identification
NCT02414139.
Editorial acknowledgement
Medical writing assistance was provided by Martin Wallace, Novartis Pharma AG.
Legal entity responsible for the study
Novartis Pharmaceuticals.
Funding
Novartis Pharmaceuticals.
Disclosure
R.S. Heist: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Corvus; Financial Interests, Institutional, Research Grant: Genentech Roche; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Debiopharm; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Apollomics; Financial Interests, Personal, Advisory Role: Tarveda; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche. E.B. Garon: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Dracen; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Neon; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Iovance; Financial Interests, Institutional, Research Grant: Dynavax; Financial Interests, Personal, Advisory Board: Novartis. H.J.M. Groen: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Lilly. D.S.W. Tan: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Merrimack; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GlaxoSmithKline. O. Tanriverdi: Financial Interests, Personal, Full or part-time Employment: Novartis. A. Robeva: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Le Mouhaer: Financial Interests, Personal, Full or part-time Employment: Novartis. M. Carbini: Financial Interests, Personal, Full or part-time Employment: Novartis. A. Chassot Agostinho: Financial Interests, Personal, Full or part-time Employment: Novartis. J. Wolf: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Ignyta; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Chugai Pharmaceutical Company; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer.