The tradition of wild biotech stock price movements on Asco Monday – when investors get their first opportunity to react to clinical data emerging over the weekend – was rather muted this year, reflecting the relative absence of high-impact late-stage trial revelations at the conference. But it would be wrong to assume that there were no biotech casualties this time around.
One of the largest stock price declines befell Mirati Therapeutics, whose shares sank 45% yesterday on a savage downgrade from Leerink citing underwhelming data for its lead asset, the c-Met inhibitor glesatinib.
The project is now in a phase II study, Amethyst NSCLC, in second-line or later non-small cell lung cancer with activating c-Met mutations. But Mirati’s Asco update was from an earlier trial: a phase Ib dose-escalation study in solid tumours with c-Met or Axl alterations. The data showed just three partial responses, one each with Met amplification, a Met exon14 deletion and Axl amplification, from the 11 patients in the study with NSCLC.
The response rate in the c-Met+ group was 20% or two of 10, down from a previously calculated 50%, two of four, last year. 10 of 11 patients experienced tumour regression, including the three responders, and at data cutoff the responders had been treated for an average of 39 weeks. Two of the three responders were still being treated at 23 weeks and 56 weeks.
Still, the response rate changes are based on very small patient numbers. The real factor behind Mirati’s stock market rout was the positive news from competing c-Met inhibitors at Asco.
Novartis reported positive early data on its c-Met inhibitor capmatinib in NSCLC patients with high c-Met amplification, showing seven partial respones in 15 patients (47%). The company is running a 276-patient phase II study in second/third-line NSCLC patients.
Meanwhile, a poster on Pfizer’s Xalkori in patients with c-Met exon14 deletions showed 10 partial responses (five confirmed, five unconfirmed) from 15 evaluable patients (67%). Moreover, this project already has a US National Comprehensive Cancer Network compendium listing for c-Met gene amplification, and already enjoys some off-label use.
Mirati intends to position glesatinib for NSCLC with c-Met alterations, which occur in 5-6% of patients. The next step is to initiate a combination study with an anti-PD-1 inhibitor. In the longer term the group hopes to exploit the fact that Met/Axl is believed to be an important EGFR resistance mechanism in patients with the EGFR T790M mutation, and it has plans to test the project in combination with a third-generation EGFR inhibitor, presumably AstraZeneca's Tagrisso.
These plans could become more difficult to fund if its share price remains depressed.
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