Clinical trials of adagrasib

On December 12, 2022, data from a Phase 1/2 trial (NCT03785249) were announced at the 2022 American Society of Clinical Oncology Annual Meeting and published in the journal Medicine. Adagrasib (600 mg orally twice daily) was evaluated in patients with KRAS G12C mutant non-small cell lung cancer who had already received platinum-based chemotherapy and immune checkpoint inhibitors. The primary endpoint was objective response assessed by blinded independent central review. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety.

During a median follow-up of 12.9 months, 116 patients with KRAS G12C mutated non-small cell lung cancer received adagrasib; 98.3% of the patients had previously received chemotherapy and immunotherapy. Among 112 patients with measurable disease at baseline, the confirmed objective response rate (ORR) was 42.9% (n=48). The median DOR was 8.5 months (95% CI 6.2-13.8), and the median PFS was 6.5 months (95% CI 4.7-8.4). The median follow-up time was 15.6 months, the median OS was 12.6 months (95% CI 9.2-19.2), and the estimated OS at 1 year was 50.8% (95% CI 40.9-60.0%).

Metastasis is common in non-small cell lung cancer and is associated with poor prognosis and quality of life. 40% of KRAS G12C- mutated non-small cell lung cancer patients develop brain metastases. In patients with previously treated stable CNS metastases (n=33), the intracranial confirmed ORR of adagrasib was 33.3 % (95% CI 18.0%-51.8%), the median duration of intracranial response was 11.2 months (95% CI 2.99 - not evaluable).

Treatment-related adverse events (TRAEs) occurred in 97.4% of patients; 53.6% of adverse events were grade 1 and 52.6% were grade 2. Notably, 44.8% of patients experienced grade 3 or higher AEs, including 2 grade 5 events. The discontinuation rate of TRAE-related drugs was 6.9%. The most common adverse events with this drug were diarrhea (70.7%) and nausea (29.8%).

BecauseadagrasibThe original drug has not yet been launched in the country, and patients can only purchase adagrasib through overseas channels. The specifications of the original version in the United States200mg*180 tablets are priced at hundreds of thousands of yuan per box (the price may fluctuate due to exchange rates), which is very expensive. Currently, there are no generic drugs of adagrasib produced overseas. For more drug information and specific prices, please consult Yaode’s medical consultant.