The KRASG12C inhibitor adagrasib shows promising efficacy in pretreated patients with advanced non-small cell lung cancer harboring a KRASG12C mutation, according to results of the KRYSTAL-1 trial presented at the 2022 ASCO Annual Meeting.
The trial (ClinicalTrials.gov Identifier: NCT03785249) has a phase 1/2 design. A total of 116 patients in a registrational phase 2 cohort were treated with adagrasib 600 mg twice daily. All had been previously treated with platinum-based chemotherapy and immunotherapy targeting programmed death 1 or programmed death ligand 1.
The overall response rate was 42.9%, with a disease control rate of 79.5%. The researchers noted that responses were deep, with 75% of responders achieving a greater than 50% tumor reduction. Treatment is ongoing in 50% of responders and 33% still have a response.
“Based upon this data, a New Drug Application for adagrasib has been accepted and is currently under review at the [Food and Drug Administration],” said study presenter Alexander I. Spira, MD, PhD, of the Virginia Cancer Specialists Research Institute in Fairfax.
Median duration of response was 8.5 months, with a median progression-free survival of 6.5 months.
With a median follow-up of 15.6 months, the median overall survival was 12.6 months. The 6-month overall survival rate was 71%, with about half (51%) of patients alive at 12 months.
The study included patients with stable central nervous system metastases. In these patients, the intracranial overall response rate was 33% and intracranial disease control rate was 85%.
According to the researchers, adagrasib was well tolerated with a manageable safety profile. Treatment-related adverse events (TRAEs) of any grade occurred in 97% of patients and of grade 3 or 4 in 43%. Two patients experienced grade 5 TRAEs. Overall, 7% of the cohort had TRAEs leading to study discontinuation.
An ongoing, confirmatory phase 3 trial, KRYSTAL-12 (ClinicalTrials.gov Identifier: NCT04685135), is comparing adagrasib monotherapy with docetaxel in this patient population.
Disclosure: This research was supported by Mirati Therapeutics, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Spira AI, Riely GJ, Gadgeel SM, et al. KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced/metastatic non–small cell lung cancer (NSCLC) harboring a KRASG12C mutation. Presented at ASCO 2022; June 3-7, 2022. Abstract 9002.