Amgen KRAS Inhibitor Shows Benefit in Phase III Lung Cancer

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X-ray of the lungs showing breast cancer

The KRAS inhibitor race drew attention this week when patients with non-small cell lung cancer a KRAS The G12C mutation had higher progression-free survival (PFS) and objective response rate (ORR) with Amgen’s KRAS inhibitor lumakras (sotorasib) compared to docetaxel, according to the results of a phase III study. The data were presented yesterday at the European Society for Medical Oncology (ESMO) 2022 Congress in Paris.

“The collective body of evidence from this study supports Lumakras as an important targeted treatment option for patients with non-small cell lung cancer who carry it KRAS G12C mutation and underscores the urgent need for comprehensive biomarker testing for all patients with advanced disease,” said David M. Reese, MD, Amgen’s executive vice president of research and development.

“We plan to share this data with health authorities around the world where Lumakras/Lumykras has conditional approvals and look forward to our discussions with regulators,” he added.

The field of KRAS inhibitors is highly competitive. Nearly 400 clinical trials of KRAS mutations are ongoing. One of the industry leaders, Mirati Therapeutics, signed a deal with Sanofi in Fall 2021 to combine the small biotech’s KRAS G12C inhibitor with the big pharma’s SHP2 inhibitor SAR442720 in a Phase I/II trial.

Lumakras is expected to receive full approval based on the most recent data. On the other hand, the drug did not show overall survival and there were new signs of liver toxicity. However, it significantly improved PFS compared to docetaxel in heavily pretreated patients. The proportion of patients with PFS at one year was 25% for Lumakras versus 10% for docetaxel.

The drug also demonstrated a significantly higher ORR than docetaxel, with response rates twice as high in the Lumakras arm (28% vs. 13%, respectively), and demonstrated consistent benefit in other secondary efficacy endpoints, notably an improved disease control rate (83% vs. 60%, respectively); shorter time to response (1.4 versus 2.8 months, respectively); and longer duration of response (DOR; 8.6 versus 6.8 months).

“This is the first randomized Phase III clinical trial of a KRAS G12C inhibitor demonstrating benefit in heavily pretreated patients who have limited treatment options,” said Melissa L. Johnson, MD, director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology and presenting author.

It is encouraging that progression-free survival benefits were consistent across clinically relevant subgroups, including those with a history of brain metastasis, and that sotorasib response rates more than doubled compared to docetaxel response rates. These data represent a major advance for the treatment of patients with KRAS G12C mutant non-small cell lung cancer.”

Lumakras is the only approved KRAS G12C inhibitor. In May 2021, the drug received accelerated approval in the United States. It is also approved in European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Qatar, Australia, Brazil, Canada, United Kingdom, Singapore. and Israel. The drug is also being studied in several other solid tumors.

KRAS G12C is the most commonKRASmutation in NSCLC. About 13% of patients with NSCLC carry the KRAS G12C mutation. The unmet medical need remains high and treatment options for KRAS G12C mutation-positive NSCLC patients who are failing or no longer responding to first-line therapy are limited. Results with other approved therapies are suboptimal, with a median progression-free survival of approximately four months after second-line treatment of KRAS G12C-mutated non-small cell lung cancer.

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