Press Release
Sep 10, 2023
Media Contact: Chris Martin, MPH, IASLC Media Relations, 630.670.2745, cmartin@davidjamesgroup.com
[Singapore -- 10:35 a.m. SGT--September 10, 2023] — The oral, selective 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 multicohort 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) granted accelerated approval of adagrasib for patients with previously treated KRAS G12C-mutated advanced/metastatic NSCLC based on data from this study in December 2022. 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 chemotherapy 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 compelling results, providing hope for patients with this specific mutation,” Dr. Gadgeel said. “Exploratory analyses indicated that adagrasib provided promising clinical benefit for a broad group of patients, including those presenting with baseline treated, stable CNS metastases and co-mutations, such as KEAP1, STK11, or TP53.”
Dr. Gadgeel said that most of the treatment-related adverse events were manageable, with the majority of adverse events being low grade, including fewer GI TRAEs with late onset in patients who were treated greater than 1 year. There were also no grade ≥3 hepatotoxicity in patients who had received prior IO within 30 days of adagrasib treatment
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.
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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 10,000 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 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.