Mirati stock dips amid trial data on adagrasib/Keytruda combo in lung cancer patients
gorodenkoff

Mirati Therapeutics (MRTX -0.1%) said its medicine adagrasib in combination with Merck's (MRK) Keytruda (pembrolizumab) showed favorable tolerability and promising preliminary efficacy in certain patients with non-small cell lung cancer (NSCLC).
The company reported preliminary results from a phase 2 trial, dubbed KRYSTAL-7, and from a group of a phase 1b study called KRYSTAL-1, evaluating adagrasib (400mg twice daily) combined with PD-1/L1 checkpoint inhibitor Keytruda as a first-line treatment of NSCLC harboring a KRASG12C mutation across all PD-L1 subgroups.
In the study 75 patients were enrolled and evaluable for safety with a median follow-up of 3.5 months (duration of treatment: 2 months).
The company said there were 39% Grade 1-2 treatment-related adverse events (TRAEs), 40% Grade 3 and 4% Grade 4 .
TRAEs led to discontinuation of both adagrasib and Keytruda in 2 patients and only Keytruda in 2 patients, the company added.
Increases in alanine transaminase (ALT)/ aspartate transaminase (AST) were consistent with either agent as a monotherapy with Grade 3 TRAEs being highest grade and total incidence of Grade 3 liver function test (LFT) increases of 9%, according to the company.
High levels of ALT/AST in blood may suggest liver damage/disease.
Mirati noted that median time from onset to an increase in ALT and AST was 26 and 37 days, respectively and one patient experienced new onset treatment-related ALT/AST increase after 3 months.
Mirati said that of the in the patients who were evaluable and received at least one on-study scan (n=53), adagrasib and Keytruda showed promising preliminary clinical activity across all PD-L1 subgroups with an objective response rate (ORR) of 49%.
In a subset of response-evaluable patients enrolled at least six months prior to the data cutoff date, 6 of 26 clinical responses occurred at second on-study scan or later, and the ORR was 56%, the company noted.In addition, 7 evaluable patients enrolled in the KRYSTAL-1 phase 1b group (with a median follow-up of 19.3 months) reported an ORR of 57% and a disease control rate (DCR) of 100%.
The company said that the four patients who responded maintained response for over nine months while two continued to receive therapy and remained in response beyond 18 months.
Mirati noted that safety in the KRYSTAL-1 phase 1b cohort was consistent with what was seen in KRSTYAL-7 and showed a manageable safety profile with no Grade 4-5 TRAEs.
"This data further underscores the potential of adagrasib as a well-tolerated treatment option for patients. Based on these data, we look forward to initiating a Phase 3 trial," said Chuck Baum, president, founder, and head of research and development, Mirati.
Mirati has a collaboration agreement with Zai Lab (ZLAB) on adagrasib.
Mirati's adagrasib, a KRAS G12C inhibitor, is currently under review in the U.S. and is similar to Amgen's (AMGN) Lumakras, which was approved by the FDA in 2021 to treat certain patients with NSCLC.
MRTX -9.97% to $83.50 premarket Dec. 6