Loading
GEOMETRY mono-1 showed that capmatinib shrinks two thirds of untreated lung cancers with a MET exon 14 skipping mutation and about four in ten after chemotherapy, which made MET exon 14 the seventh lung cancer driver with an approved targeted drug.
GEOMETRY mono-1 enrolled patients with advanced non-small-cell lung cancer into cohorts defined by MET exon 14 skipping or by the degree of MET amplification and by prior treatment, all receiving capmatinib 400 mg twice daily. MET exon 14 skipping, found in 3 to 4 percent of lung cancers and often in older patients and sarcomatoid tumours, had responded poorly to the multikinase inhibitor crizotinib.
Among the exon 14 cohorts the response rate was 68 percent in 28 treatment-naive patients and 41 percent in 69 previously treated patients, with median durations of response of 12.6 and 9.7 months and activity against brain metastases. Tumours with high MET amplification (gene copy number 10 or more) responded in about a third of cases; lower levels of amplification did not respond. Peripheral oedema and nausea were the main side effects.
The FDA granted accelerated approval in May 2020 and regular approval in 2022; tepotinib (VISION) followed with similar results, and the two drugs are interchangeable options.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate, MET exon 14 skippingprimary | Treatment-naive | 28 | 68% | - | - | link |
| Previously treated | 69 | 41% |
A second publication from the GEOMETRY mono-1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
A rare driver with a real drug, and a warning about biomarker thresholds: the same gene, tested the same way, predicts response or does not depending on a copy-number cut-off that has to be measured rather than assumed.
Shares Capmatinib, MET amplification (bypass resistance), Crizotinib, MET exon 14 and MET-amplified non-small-cell lung cancer.
Shares Capmatinib & tepotinib, MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Lung cancer (all types).
Shares Capmatinib, Crizotinib, MET exon 14 and MET-amplified non-small-cell lung cancer, MET.
Shares Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer, Capmatinib, MET exon 14 and MET-amplified non-small-cell lung cancer, MET.
Shares Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Non-small-cell lung cancer.
Shares MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Non-small-cell lung cancer.
Shares Capmatinib, MET amplification (bypass resistance), Crizotinib, MET.
Shares Capmatinib & tepotinib, Capmatinib, MET, Non-small-cell lung cancer.