Amgen Racks Up Success in Phase II Lung Cancer Trial

Amgen

Amgen announced data from the Phase II cohort of the CodeBreaK 100 trial of sotorasib (AMG 510) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). They plan to present the data during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASCLC) 2020 World Conference on Lung Cancer (WCLC).

The drug demonstrated a confirmed objective response rate (ORR) of 37.1% and a disease control rate (DCR) of 80.6% and a median duration of response of 10 months. It was also the first KRASG12C to demonstrate progression-free survival, with a median of 6.8 months in a Phase II trial.

During the trial, patients received 960 mg of sotorasib once a day orally. Before the trial, 81% of the patients had disease progression on both platinum-based chemotherapy and checkpoint inhibitors, while the remaining 19% progressed after receiving one of those therapies.

“Patients with advanced non-small-cell lung cancer who have failed first-line treatment face extremely poor outcomes with limited treatment options available to them, and Amgen has been committed to changing that,” said David M. Reese, executive vice president of Research and Development at Amgen. “Targeting KRAS has been a 40-year quest by scientists and researchers around the world, and we are extremely pleased that sotorasib has successfully demonstrated rapid, deep and durable responses in this registrational Phase II study that was conducted in record time. We are proud that sotorasib may potentially become the first approved targeted therapy for these patients.”

Of the patients in the trial, 80% achieved disease control. There were three complete responses and 43 partial responses, with a 60% median best tumor shrinkage among all responders. It was 1.4 months to median time to objective response.

The benefit-risk profile with most treatment-related adverse events (TRAE) was favorable, with mild-to-moderate grade 1 or 2 and no treatment-related deaths. Grade 3 treatment-related adverse events were reported in 25 patients and one patient reported a Grade 4 TRAE.

The most common TRAEs of any grade were diarrhea, nausea, increased alanine aminotransferase and increased aspartate aminotransferase. TRAEs only caused treatment discontinuation in 7.1% of patients.

At this point, there are no KRAS inhibitors approved.

Michael Yee, an analyst with Jefferies, wrote in a note to clients, “This was expected to be positive already so this is just confirmation the data is good and is already under review by the FDA, and as the prior top-line disclosure by the company stated the efficacy is ‘consistent’ with Phase I results.”

Greg Friberg, Amgen’s vice president of global oncology development, noted that the 6.8 months was favorable to what is generally seen as two to four months for drugs like docetaxel. “Essentially, what we’re answering is this drug looks like it has consistent, deep, durable responses and very promising survival numbers at this point. We are hopeful this is the beginning of our opportunity to deploy the drug into different settings.”

It is being tested against docetaxel in a Phase III trial in previously treated patients, while also running a single-arm Phase II trial in the first-line setting to determine which patients will receive the most benefit from sotorasib as a monotherapy. It is also evaluating 10 different drug combinations with sotorasib in an adaptive study. The combinations include antibodies and EGFR kinase inhibitors, SHP2 inhibitors, MEK inhibitors and PD-1 checkpoint inhibitors.

Amgen plans to test sotorasib in earlier lines of therapy and in combination with other cancer drugs. Currently, Amgen is hoping for approval in the U.S., UK, European Union, Canada, Australia and Brazil.

“These results are encouraging and clinically meaningful for patients with advanced NSCLC harboring the KRAS G12C mutation,” said Bob T. Li, medical oncologist and principal investigator at Memorial Sloan Kettering Cancer Center. “These are patients who have progressive disease after standard treatment, so they need additional treatments, and the fact that we are seeing rapid tumor shrinkages and durable responses in these patients, is for me a step forward and a win for patients.”

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