KRYSTAL-1 trial finds that adagrasib demonstrates durable clinical activity in patients with KRAS-G12C mutations

[Singapore — 10:35 a.m. SGT–September 10, 2023] — The oral, selective KRAS G12C inhibitor  The oral, selective KRAS G12C inhibitor  KRAS-G12C inhibitor adagrasib demonstrated durable clinical activity, with a median overall survival of 14.1 months and approximately one in three patients alive at two years, according to research presented today at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer in Singapore.

KRAS-G12C mutations occur in approximately 14% of patients with NSCLC. The KRYSTAL-1 study, a multi-cohort Phase 1/2 trial, evaluated adagrasib as a monotherapy or in combination for patients with KRAS-G12C-mutated solid tumors. The U.S. Food and Drug Administration (FDA) already granted accelerated approval of adagrasib for patients with previously treated KRAS-G12C-mutated advanced/metastatic NSCLC based on data from this study. Additionally, the European Medicines Agency (EMA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) are currently reviewing the drug.

In the two-year follow-up, pooled analysis of the Phase 1/1b Cohort and Phase 2 Cohort A, 132 patients with KRAS-G12C-mutated NSCLC were treated with adagrasib 600 mg orally twice daily. The median age of patients was 64 years, with 56.8% being female. At baseline, 19.7% of patients had central nervous system metastases. Patients had received a median of two prior therapies, including platinum-based and checkpoint inhibitor therapies.

According to Shirish Gadgeel, MD from Henry Ford Cancer Institute, Henry Ford Health System, in Detroit, Mich., the results showed a favorable objective response rate (ORR) of 43.0%, with a median duration of response (DOR) of 12.4 months. The median progression-free survival (PFS) was 6.9 months, and the median overall survival (OS) was 14.1 months. Notably, 52.8% of patients were still alive at one year, and approximately one in three patients (31.3%) remained alive at two years. The findings suggest durable clinical activity of adagrasib for KRAS-G12C-mutated NSCLC.

“The study data demonstrates promising results, providing hope for patients with this specific mutation,” Dr. Gadgeel said. “Exploratory analyses indicated that the presence of co-mutations, such as KEAP1, STK11, or TP53, may impact the clinical benefit of adagrasib and warrant further investigation.”

Dr. Gadgeel reported that treatment-related adverse events were manageable, with grade ≥3 TRAEs occurring in 40.9% of patients. Only 2.3% of patients experienced grade 5 TRAEs, including pneumonitis, cardiac failure, and pulmonary hemorrhage.

The ongoing Phase 3 trial evaluating adagrasib monotherapy compared with docetaxel in previously treated advanced KRAS-G12C-mutated NSCLC holds great promise and could further establish adagrasib as an essential treatment option for patients with this specific mutation, he reported.

About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association’s membership includes more than 8,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit http://www.iaslc.org for more information.

About the WCLC:

The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration, and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc2023.iaslc.org.