- Mirati Therapeutics on Monday offered a limited glimpse at the first trial results for a combination of its experimental KRAS-blocking drug and Merck & Co.'s Keytruda, giving a much-anticipated update as the San Diego-based biotech attempts to convince investors its treatment can challenge Amgen's rival medicine Lumakras.
- Results disclosed by Mirati are preliminary and come from just eight previously untreated patients with advanced lung cancer who were given the two drugs in an early-stage study. But the data show some early promise; treatment shrank tumors in all seven patients evaluable for efficacy, four of whom were judged to have had a partial response. Another had surgery to remove their tumor before meeting the official criteria for response.
- Mirati didn't release much safety information, saying only that side effects to the two drugs were "manageable." No deaths or side effects classified as the most severe were reported, nor did any participant drop out of the study due to the treatments.
Mirati's drug, called adagrasib, is particularly closely watched. After Lumakras, which won U.S. approval earlier this year, it's the most advanced experimental drug targeting a cancer-linked gene called KRAS that's often mutated in tumors of the lung, colon and pancreas. Only recently, after decades of unsuccessful attempts, have researchers discovered ways to effectively target KRAS mutations in cancer.
A handful of drugmakers, including Novartis, Johnson & Johnson, Roche and Boehringer Ingelheim, now aim to follow in Amgen's footsteps, with Mirati the furthest along. In September, the biotech released Phase 2 study results showing treatment with adagrasib led to partial tumor responses in 43% of patients with previously treated non-small cell lung cancer.
Other data unveiled at the same time suggested adagrasib could match or potentially surpass Lumakras's efficacy in colon cancer.
While Lumakras and adagrasib represent major advances in targeting KRAS-driven cancers, both are only modestly effective in keeping tumors in check and don't work in a majority of patients. Amgen and Mirati, along with other developers, are therefore investing considerable resources in exploring combination treatments.
The data released Monday are the first from Mirati and give it a slight head start on Amgen, which doesn't expect trial results for Lumakras and Keytruda until the first half of next year. But the small number of patients included mean definitive conclusions are difficult to reach. Moreover, the response rates could change as more participants in the study are treated or are followed for longer.
Five of the seven patients evaluated for Monday's update remained on treatment, with a median follow-up of just under 10 months, Mirati said.
The response rate — four of seven had confirmed partial responses — just about matches the bar of between 50% to 60% that analysts at SVB Leerink set for success in a Nov. 1 note to clients. The number of patients included in the update is less than some other analysts had expected, however, and Mirati did not break out subgroups by expression of a protein associated with immunotherapy response.
A larger Phase 2 trial of the two drugs together in previously untreated advanced lung cancer is ongoing and data is expected in the second half of next year.
For Mirati, the update comes amid significant upheaval in the company's leadership. In September, David Meek, a former chief executive at Ipsen and FerGene, was appointed as Mirati's CEO, taking over for Charles Baum. Then, on Nov. 1, the company announced its chief operating officer and chief medical officer were both stepping down.
Shares in Mirati, which is worth about $8 billion, have declined by nearly 30% to date this year.
Mirati expects to finish filing an application with the Food and Drug Administration for approval of adagrasib in patients with previously treated non-small cell lung cancer by the end of the year.
Note: This story has been updated with additional information on when data will be available from Mirati's Phase 2 study of adagrasib with Keytruda in advanced lung cancer.