MET-mutations and MET-amplifications are reported in 1-6% of patients with NSCLC.

In a phase 2 basket trial Sym015, a mixture of antibodies targeting MET, was well tolerated and demonstrated clinical activity in 20 patients with MET-exon14 skipping deletion or MET-amplification non-small cell lung cancer (NSCLC), researchers reported at the virtual meeting of the American Society of Clinical Oncology.

“The two monoclonal antibodies of Sym015 bind to non-overlapping epitopes on MET”, explained Ross Camidge, Professor of Medicine and Medical Oncology at Colorado University, Denver, USA. “The particular importance of this approach is that it’s an additional way of downregulating MET signaling separate from that of tyrosine kinase inhibitors and may well work when kinase inhibitors fail because of kinase domain mutations.” In this phase 2 basket trial, 45 patients were treated with Sym015, including 20 NSCLC patients. Ten NSCLC patients were MET TKI-naïve, and 10 had been previously treated with a MET-directed therapy. Both groups had a mixture of tumors with MET-amplifications and with deletions resulting in MET-exon 14 skipping.

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“Sym015 was well tolerated. There were relatively few dose reductions and in de NSCLC population peripheral edema, some fatigue, some mild gastrointestinal were the most common side effects”, reported Camidge. “Six out of 45 patients experienced grade 3 adverse events, but no patients had to discontinue the treatment because of adverse events.” Many the NSCLC patients were able to stay on the treatment for quite a long period of time. The average was 4.6 months, 5.2 months in those who were MET TKI-naïve, and 3.5 in those who were MET TKI pre-treated.

In MET TKI-naïve NSCLC patients, Sym015 was an active agent (50% overall response rate, 100% disease control rate) whereas in NSCLC patients who had previously had treatment with a MET TKI, only minor responses were observed. The trial also showed that circulating tumor DNA (ctDNA) was highly concordant for MET-exon 14 skipping deletions, but was not robust in detecting MET-amplification.

Camidge R, et al. ASCO 2020 virtual meeting, abstract 9510.