On December 5, 2022, Zai Lab announced that its partner Mirati Therapeutics released the latest clinical data on the KRAS G12C inhibitor Adagrasib combined with the PD-1 inhibitor pembrolizumab first-line treatment of with KRAS G12C mutation non-small cell lung cancer (NSCLC).
Previously, in June 2021, the US FDA awarded Adagrasib breakthrough therapy certification for the treatment of with KRAS G12C mutations and treated non-small cell lung cancer patients.
On February 15, 2022, the US FDA has accepted the new drug launch application for for the treatment of non-small cell lung cancer patients with KRAS G12C mutation and have previously received at least once systemic treatment of .
Adagrasib is a powerful oral KRAS G12C inhibitor with highly specific that binds irreversibly and selectively to KRAS G12C and locks it in an inactive state, with a long half-life to achieve durable and continuous KRAS inhibition and lead to deep and lasting anti-tumor activity. Adagrasib research shows that the drug has a long half-life of and a wide distribution of tissues, and has good tolerance to . The results of the study show that Adagrasib has shown a single-agent effect in non-small cell lung cancer, colorectal cancer, pancreatic cancer and other KRAS G12C mutations.
General name: Adagrasib
Code: MRTX849
Target: KRAS G12C
The first time approved in the United States: 1 not approved
1th time approved in the country: not approved
clinical data
clinical data
KRYSTAL-7 test and KRYSTAL-1 test are mainly used to evaluate KRAS The efficacy and safety of G12C inhibitor Adagrasib and PD-1 inhibitor pembrolizumab as first-line treatment for patients with KRAS G12C mutations. The results of the
trial showed that a total of 75 patients were enrolled in the trial and the safety was assessed, with a median follow-up time of 3.5 months.
in patients who were clinically evaluated and had undergone at least one study scan (n=53), Adagrasib combined with pembrolizumab showed initial clinical activity in all PD-L1 subgroups, with an objective response rate (ORR) of of 49% . In addition, in the subgroup of evaluable responses enrolled at least 6 months ago in the data, clinical responses occurred in 6 of 26 patients after or after the second study scan, with an ORR of 56%. In the
KRYSTAL-1 phase 1b cohort, the median follow-up time was 19.3 months, and the 7 evaluable patients had ORR of 57% , and the disease control rate (DCR) was 100% . Among them, 4 patients had continuous remission for more than 9 months, and 2 patients continued to receive treatment and continued remission for more than 18 months.
Safety
In terms of safety, treatment-related adverse events (TRAEs) were grades 1-2 (39%), grade 3 (40%) and grade 4 (4%), and no grade 5 TRAEs were observed. TRAEs resulted in two patients discontinuing Adagrasib and pembrolizumab, two patients discontinuing Pembrolizumab, and none of them discontinuing Adagrasib because of TRAE.
Among them, the grade 3 alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) is consistent with any drug as a monotherapy, and the overall incidence of grade 3 liver function test (LFT) increased by 9%. The median time from administration to ALT and AST elevations was 26 days and 37 days, respectively, and only 1 patient showed new treatment-related ALT/AST elevations after 3 months. The safety of the phase Ib cohort of
KRYSTAL-1 trial is consistent with that observed in the KRYSTAL-7 trial and demonstrates controllable safety without grades 4-5 TRAEs.
summary
preliminary trial results show that Adagrasib combined with pembrolizumab may provide a chemotherapy-free option for patients with initial treatment of NSCLC. This treatment regimen has controllable safety and encouraging clinical activity. Among all evaluable cohorts, liver-associated TRAEs were mainly low-grade, occurring early in the treatment phase, and the possibility of reoccurring after 3 months was limited.
Reference source:
https://ir.zailaboratory.com
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