#AACR20: Early data suggest Novartis' Incyte-discovered MET inhibitor helps lung cancer patients with brain lesions
Months after capmatinib — the MET inhibitor designed to cross the blood-brain barrier discovered by Incyte and licensed by Novartis — secured the FDA’s priority review in patients with a form of lung cancer, the Swiss drugmaker has reported encouraging, albeit early, data in patients whose cancer had spread to the brain.
Data from 13 patients with metastatic MET exon 14 skipping non-small cell lung cancer with brain metastases, were unveiled at the virtually-held American Association for Cancer Research conference on Monday.
Data from the mid-stage GEOMETRY mono-1 study showed that 7 of the 13 experienced an intracranial response, of which 4 had a complete resolution of all brain lesions.
The trial enrolled 97 heavily pre-treated (cohort 4) and treatment-naive (cohort 5b) patients altogether at the April 15 cutoff.
The overall response rate — the study’s main goal — was 40.6% in pre-treated patients versus 67.9% in the treatment-naive group. The median duration of response, a key secondary endpoint, was 9.72 months in pre-treated patients compared to 11.14 months in the treatment-naive arm. Another secondary goal, median progression-free survival, also favored the treatment-naive arm with 9.69 months, against 5.42 months in the previously treated patients.
From a safety standpoint, capmatinib was manageable. The most common toxicity-related adverse events across all cohorts were peripheral edema, nausea, increased blood creatinine and vomiting.
There are currently no approved therapies that specifically target MET exon 14 skipping non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of lung cancer diagnoses, while MET exon 14 skipping mutations occur in 3-4% of newly diagnosed advanced NSCLC cases.

Novartis chief Vas Narasimhan has touted the therapy as one of seven potential blockbusters the company is hoping to bring on to the market in 2020 — if capmatinib is launched, original discoverer Incyte stands to earn over half a billion dollars in milestone payments and royalties. The drug has also been granted breakthrough status and priority review for MET exon 14 skipping lung cancer, with an FDA decision expected by August.
Pfizer’s rival MET and ALK inhibiting rival drug, Xalkori, was granted breakthrough therapy status in patients with metastatic NSCLC with MET exon 14 mutations who had received prior therapy in 2018. In January, the US drugmaker disclosed data on 65 evaluable patients. Data showed the therapy-induced median duration of response was 9.1 months and median progression-free survival of 7.3 months.