KRAS clinical trial shows promise for new targeted treatment

Potentially First Approved KRAS Treatment

From Reuters:

An experimental Amgen Inc drug that targets a specific genetic mutation reduced tumor size in around half of advanced lung cancer patients given the highest dose in a small, early-stage trial, the company said on Sunday.

Out of 13 lung cancer patients taking a 960-milligram dose of AMG510, seven had tumors shrink by at least 30%, according to data presented in Barcelona at the World Conference on Lung Cancer. Cancer was stabilized in the other six high-dose patients.

Nine of the 13, or 69%, are still taking the daily pill. Two of the partial responders have died, and another left the study due to cancer progression. One patient with stable disease also died.

Patients who responded to the drug have been treated for a median of 15 weeks, but the median duration of response has not been reached, according to Greg Friberg, head of oncology development at Amgen.

He said one patient previously reported as free of lung cancer is being counted as a partial responder since cancer in lymph nodes or other tissue cannot be ruled out.

Thirty-four lung cancer patients are enrolled in the Phase 1 dose-ranging trial, but Amgen has moved only the highest dose into a mid-stage study. The trial enrolled patients with tumors carrying the targeted mutation whose cancer had worsened despite several previous treatments – including chemotherapy and checkpoint inhibitors.

Of the 23 lung cancer patients so far evaluated – at various doses of AMG510 – 11 had tumor shrinkage of at least 30%.

About a third of trial patients reported mild side effects. More serious side effects, diarrhea and anemia, were seen in 9%of patients and no one left the study due to toxicity, the company said.

Wall Street has taken a keen interest in the Amgen drug that could become the first approved medicine targeting a mutated form of a gene known as KRAS – one of the most common mutations found in non-small cell lung cancer (NSCLC).

NSCLC accounts for up to 85% of lung cancers, by far the leading cause of cancer death among men and women, according to the American Cancer Society.

AMG510 is part of a growing trend of precision medicines that target gene mutations driving cancer regardless of the organ in which the disease originated.

The targeted mutation, KRASG12C, occurs in around 13% of NSCLC cases, as well as 3-5% of colorectal cancers and up to 2% of other solid tumor cancers, including pancreatic.

Amgen plans to present Phase 1 AMG510 trial results for patients with colorectal cancer later this month at a separate meeting to be held in Barcelona, this one by the European Society for Medical Oncology.

The company is also enrolling patients in an early-stage study of AMG510 in combination with Keytruda, Merck & Co’s checkpoint inhibitor designed to unleash the body’s immune system to attack cancer cells.

Amgen said the U.S. Food and Drug Administration has granted “fast track” status to AMG510 for previously treated NSCLC with KRASG12C mutation.

Rivals such as Mirati Therapeutics Inc are also developing drugs that target KRAS mutations, but Amgen’s could be first to market.