Courtesy of Getty Images
Shares of Mirati Therapeutics fell about 8% in after-hours trading Monday, despite reported positive data for adaglasib in first-line non-small cell lung cancer (NSCLC) patients.
The combination of adaglasib and Merck’s Keytruda (pembrolizumab) showed positive preliminary data from the KRYSTAL-7 Phase 2 trial and the KRYSTAL-1 Phase 1b cohort in the first-line treatment of patients with advanced/metastatic NSCLC with KRASG12C mutations I was.
“These data reinforce the potential of adaglasib as a potent treatment option for NSCLC patients with KRASG12C mutations,” said David Meek, CEO and Director of Mirati. bio spaceAdagrasib is currently under review for accelerated FDA approval in this patient population, with a target execution date of December 14.
Meek said this is the largest dataset to date evaluating a combination of a checkpoint inhibitor and a KRASG12C inhibitor as a first-line treatment option for NSCLC patients with KRASG12C mutations.
“Based on these data, we look forward to initiating a Phase 3 trial,” said Chuck Baum, President, Founder and Head of Research and Development at Mirati, in a press statement.
Mirati will host a conference call on Wednesday.
“The data continue to support the differentiated positioning of the regimen relative to standard of care, [Amgen’s] Lumaclas Plus (immunotherapy),” JP Morgan analyst Eric Joseph wrote in a research note for investors.
Adaglasib is a highly selective, potent, oral small molecule designed to inhibit KRASG12C. Keytruda is Merck’s anti-PD-L1 checkpoint inhibitor.
Various studies have shown that adaglasib has a long half-life, is widely distributed throughout the body, and has a reasonable safety profile. It is being evaluated in several clinical trials in combination with other agents in advanced solid tumors, with ongoing enrollment-enabling trials in NSCLC and colorectal cancer.
The latest data showed that the drug combination helped approximately half of treatment-naïve mNSCLC patients with manageable side effects. Mirati suggests the biggest benefit will be in patients with low PDL1 levels in her, and plans to start a Phase III trial in just that patient population, Meek said.
The study enrolled 75 patients who were evaluable with a median follow-up of 3.5 months. Treatment-related adverse events (TRAEs) were primarily grades 1, 2 and 3, with only 4% grade 4 and none grade 5. Only 2 patients discontinued both drugs because of her TRAEs and 2 patients discontinued Keytruda. No patient discontinued adaglasib.
This dual therapy showed promising early clinical results in all PD-L1 subgroups of evaluable patients, with an objective response rate of 49%. Her ORR in the subset of response-evaluable patients enrolled at least 6 months before data cutoff was 56%.
Among the 7 patients in the KRYSTAL-1 phase Ib cohort, there was an ORR of 57% and a disease control rate (DCR) of 100%. Her four patients who responded maintained their response for more than nine months, and two continued to receive treatment and maintained their response for more than 18 months.
Pasi A. Janne, MD, Ph.D. With the Dana-Farber Cancer Institute in a press release.
Late last week, Mirati announced plans to complete an analysis of another NSCLC program. The Phase 3 SAPPHIRE trial is evaluating citravatinib in combination with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo. This combination is being developed as her 3rd or 4th line treatment for patients with NSCLC. The company plans to conduct final data analysis by mid-2023.
Acquisition Rumors Continue
Mirati has been rumored to be an acquisition target for some time. Last year, Merck was said to be considering buying the company. About two weeks ago, rumors swirled again that Mirati was an acquisition target, but no specific buyer was mentioned. bloomberg.
The company has a market capitalization of $5.1 billion and would be a target for companies interested in bolt-on deals to boost their oncology pipeline. Its pipeline includes adaglasib, MRTX1133, citravatinib and MRTX1719, a synthetic lethal PRMT5 inhibitor.
Mirati also has a program for discovery of mutant KRAS inhibitors in solid tumors and a program for KRAS signal-modifying compounds that inhibit SOS1 in solid tumors.
