Research drug adagrasib also shows activity in lung cancer metastases to the brain – News Pharmacology and Drugs

According to the results of a study conducted by researchers at the Dana-Farber Cancer Institute.

Mutations in a strong oncogene known as KRAS occur in about one in four patients with NSCLC, and about 13% of tumors in NSCLC patients are caused by a specific KRAS mutation called G12C. KRAS mutations have long been considered nearly impossible to attack with targeted drugs after many years of research attempts. However, in 2021, the targeted drug, sotorasib, became the first drug approved by the Food and Drug Administration for NSCLC patients whose tumors harbor a G12C mutation, based on a clinical trial showing a response rate of 36% in these patients after initially receiving treatment. With chemotherapy and an immune checkpoint inhibitor PD-1.

The results of the new phase II trial will be presented at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO) and simultaneously published in New England Journal of Medicine, Researchers led by Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Tumors at Dana-Farber, show that treatment with KRAS is different.G12C The mutagenesis inhibitor adagrasib gave an objective response rate of 42.9% and a median overall survival rate of 12.6 months in a group of 112 patients who had previously received both chemotherapy and immunotherapy with the PD-1 immune checkpoint inhibitor. Notably, adagrasib treatment also achieved a response rate of 33.3% in 33 patients with stable metastatic lesions of the brain and central nervous system that had spread from lung tumors.

“These data demonstrate that inhibition of KRASG12C It may lead to clinically meaningful benefits for NSCLC patients with this type of lung cancer,” Jänne said. “Brain metastases are difficult to treat and having a pharmacological agent that shows activity in this setting is progress and moving in the right direction.

KRAS . patientsG12C He had few options after chemotherapy and initial immunotherapy stopped working. In the new adagrasib clinical trial, the median progression-free survival (how long patients live before their cancer begins to progress again) was 6.5 months and the median duration of response was 8.5 months. The drug is taken orally twice daily.

Because KRASG12C Cancer cells usually continue to multiply, and researchers believe that continued inhibition of drugs may be necessary. Therefore, adagrasib has been optimized to have favorable properties including a long half-life (23 hours) and the ability to enter the central nervous system. Clinical activity of adagrasib has been demonstrated in patients with other KRASG12C Tumors, including colorectal, pancreatic, bile duct, and other types of cancer.

This clinical trial was sponsored by Mirati Therapeutics, Inc.

KRYSTAL-1: activity and safety of Adadagrasib (MRTX849) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with KRASG12C The boom (Abstract 9002) will be presented by Alexander I. Spira, MD, PhD, Virginia Research Institute of Cancer Research, during the Oral Summaries Session on Non-Small Cell Lung Cancer – Metastatic Non-Small Cell Lung Cancer Friday, June 3, 2022.

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Material provided by Dana-Farber Cancer Institute. Note: Content can be modified according to style and length.

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