Novartis and Merck KGaA have both reported phase 2 results with drugs designed to treat a rare form of non-small cell lung cancer (NSCLC), setting up a race to approval.
Novartis’ capmatinib and Merck’s tepotinib both target the MET-signalling pathway, which is mutated in 3% to 5% of NSCLC cases and tends to cause aggressive tumours with a poor prognosis for patients.
At this week’s ASCO congress, Novartis presented the phase 2 GEOMETRY mono-1 trial of capmatinib in locally-advanced or metastatic NSCLC patients with MET exon 14 skipping mutations, testing a 400mg twice-daily oral dose of the drug.
The results revealed an overall response rate of 68% among 28 treatment-naive patients and 41% among a cohort of 69 previously-treated patients, with a median duration of response of 11.1 and 9.7 months, respectively.
There was also evidence that capmatinib was able to tackle lesions that had metastasised to the brain, with seven of 13 patients in this category showing a response and “including some cases of complete resolution of brain lesions,” according to lead investigator Juergen Wolf of University Hospital Cologne in Germany.
Merck presented the results of its phase 2 VISION study of a once-daily 500mg dose of tepotinib at ASCO, which also recruited both treatment-naïve and pre-treated patients with MET exon 14 skipping NSCLC tumours.
The drug achieved objective responses in 50% of 57 patients identified by a MET mutation blood test and 45% among 58 patients identified by tissue biopsy, and the median duration of response ranged from 12 to 17 months – depending on the diagnostic used and the assessment by the trial investigators or an independent review committee.
Tepotinib also seemed to work in patients with brain metastases who “benefitted equally” from treatment, according to lead investigator Paul Paik of Memorial Sloan Kettering Cancer Centre in the US.
Direct comparisons between the two drugs are difficult at this stage, but the encouraging thing is that both seem to have activity in a patient group that has no targeted therapeutic options at the moment and are typically treated with platinum chemotherapy.
While the number of patients in the studies is fairly small, both Novartis and Merck think their studies have the potential to be used as registration trials, subject to the agreement of regulators.
The data also mark an inflection point for the MET inhibitor class, which have been in development for decades but have been in search of a suitable indication to give them a clear path to regulatory approval.
The FDA has awarded capmatinib orphan and breakthrough designations in METex14 NSCLC, while tepotinib has also picked up fast-track status from the US regulator for the same indication.