Mirati Therapeutics Releases Positive Results of Adagrasib for Treatment of NSCLC

Findings of the phase 2 cohort and the phase 1b cohort of the KRYSTAL-1 study are being presented at the 2022 American Society of Clinical Oncology Annual Meeting.

Mirati Therapeutics announced positive results from the phase 2 cohort of the KRYSTAL-1 study, evaluating adagrasib at the 600-mg strength twice-a-day in individuals with non–small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least 1 prior systemic therapy.

The findings were presented on June 3 at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

“The positive and encouraging data from this trial further support the scientific rationale for targeting the KRASG12C mutation with adagrasib, which fully and continually inhibits mutant KRASG12C throughout the entire dosing period,” Alexander Spira, MD, PhD, FACP, co-director at the Virginia Cancer Specialists Research Institute, said in the statement. “This important dataset demonstrates positive clinical activity with adagrasib across molecular and clinical subgroups, including patients with treated and stable CNS metastases.”

As of October 15, 2021, there were 116 individuals enrolled and treated in the study. Of the individuals, 98% had prior treatment with a PD-1/L1 inhibitor following or in combination with chemotherapy.

The median time for follow up was 12.9 months.

Of the individuals who were evaluated for a response, the initial results showed that the objective response rate (ORR), by Blinded Independent Central Review, was 43%. Additionally, the disease control rate (DCR) was 80%, and the median duration of response (DOR) was 8.5 months.

Furthermore, investigators found that the median progression-free survival (PFS) was 6.5 months.

At the cutoff date of January 15, 2022, the median overall survival (OS) was 12.6 months.

The safety profile of adagrasib was consistent with prior reports, and there were no new safety signals observed. The most frequent treatment of treatment-related adverse events (TRAEs) included gastrointestinal issues and fatigue.

The majority of TRAEs were grade 1 or 2, with just 43% of individuals experiencing TRAEs that were grade 3 or 4.

Just 2 grade 5 TRAEs were observed, and TREAs led to discontinuation of therapy in just 7% of individuals.

Additionally, the company will present results from the phase 2 NSCLC cohort of the KRYSTAL-1 study evaluating adagrasib in individuals with KRASG12C-mutated NSCLC and stable, previously untreated central nervous system (CNS) metastases.

“The data from the registrational lung cancer cohort of KRYSTAL-1, including the clinical activity shown in patients with stable, previously treated CNS metastases, further support adagrasib’s unique profile,” Charles Baum, MD, PhD, president, founder, and head of research and development at Mirati, said in a statement. “Mirati is at the forefront of KRAS research, and we are pleased with the meaningfully positive clinical outcomes patients are experiencing with adagrasib, both in previously treated lung cancer and in other tumor settings,”.

The findings showed that CNS-specific activity, including a 33% intracranial (IC) ORR by response assessment in neuro-oncology-brain metastases and the IC DCR was 85%.

The company reported updated findings from the pooled analysis of a total of 132 individuals in the KRYSTAL-1 study, including phase 2 and phase 1/1b NSCLC cohorts, evaluating adagrasib at the dosage of 600 mg, twice a day.

As of October 15, 2021, the results from the analysis showed an ORR of 44% and a DCR of 81%, based on central independent review.

Additionally, the median DOR was 12.5 months, and the median PFS was 6.9 months. At the cutoff date of January 15, 2022, the median OS was 14.1 months.

Further, the safety and tolerability were consistent with previous reported findings for individuals with advanced NSCLC.

These data will be presented at a future medical congress.

On June 6, 2022, the company will present late-breaking results from the phase 1b cohort of the KRYSTAL-1 study evaluating the drug in active, untreated CNS metastases at the ASCO meeting.

Reference

Investigational adagrasib delivers positive results in registration-enabling study of patients with KRASG12C-mutated advanced non–small cell lung cancer. Mirati Therapeutics. News release. May 26, 2022. Accessed June 1, 2022. https://ir.mirati.com/press-releases/press-release-details/2022/Investigational-Adagrasib-Delivers-Positive-Results-in-Registration-Enabling-Study-of-Patients-with-KRASG12C-Mutated-Advanced-Non-Small-Cell-Lung-Cancer/default.aspx