Mirati triumphs again in KRAS-mutated lung cancer with a closely watched FDA filing now in the cards
After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.
In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.
It’s the latest update from the KRYSTAL study, which is testing adagrasib as a monotherapy and in combinations across multiple solid tumor types. Data from the Phase I portion of that study in NSCLC piqued investors’ interest, with a 45% response rate that appeared to rival registrational data for Amgen’s sotorasib — now approved and marketed as Lumakras — in the same indication.
Now, the Phase II monotherapy data, which Mirati is calling “potentially registration-enabling,” back up those early results and appear good enough to put adagrasib on the path to approval and into a head-to-head competition with sotorasib. Mirati plans to file its NDA for the drug in the fourth quarter, the biotech said in a release.
But full results from this cohort, including complete and partial responses and safety data, will have to wait for a medical meeting early next year, Mirati said. Adagrasib posted an 80% disease control rate on June 15 with 98.3% of patients previously treated with immunotherapy and chemo.
It’s been a busy weekend at #ESMO21 for Mirati and its closest competitor with competing data releases in colorectal cancer, which is expected to be the next battleground for both drugs. On Sunday, Mirati released data from the Phase II portion of KRYSTAL showing solo adagrasib posted a response rate of 22% in colon cancer patients with at least two prior lines of therapy, per investigators, with one unconfirmed partial response reported.
The drug posted a disease control rate of 87% at a median 8.9-month follow up, with a median duration of response of 4.2 months and median progression free survival of 5.6 months.
Meanwhile, an adagrasib-cetuximab combo posted a response rate of 43% in 28 evaluable patients with two unconfirmed partial responses and a disease control rate of 100% at a median seven-month check-in. After the data cutoff, one of those partial responses was confirmed, Mirati said, while the other PR had progressed.
On Thursday, Amgen unveiled Phase Ib/II data showing a combo of sotorasib and EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer with KRAS-G12C. The 27% overall response rate in the initial 26 patients, which included five patients who saw tumor growth after treatment with sotorasib monotherapy, was a far cry better than the 7.1% response rate the drug posted solo in a Phase I test, later updated to 9.3%.
In an unusual email late Sunday, an Amgen spokesperson sent a lengthy statement pointing out the dangers of cross-trial comparisons and touting the drugmaker’s planned strategy to pursue sotorasib combinations for CRC, including a planned third-line-or-later Phase III study.
But on sheer numbers alone, Mirati at the very least looks like a strong competitor for Lumakras, which hit the market in NSCLC first and provided proof of concept for KRAS inhibitors on the whole. More data will certainly clarify differences between the drugs, but Mirati appears to like where it currently stands.