You’d think Amgen would still be celebrating in the halls after scoring an FDA approval for the KRAS inhibitor Lumakras just one week ago, but there’s just too much to do.
The Thousand Oaks, California-based biotechnology company is instead looking to a new cohort from the drug's pivotal trial, which is beginning to reveal the patients most likely to benefit from the drug, formerly known as sotorasib.
The new data, revealed Friday at the virtual American Society of Clinical Oncology meeting, could help Amgen move Lumakras up in the line of treatment for non-small cell lung cancer patients, a goal the company is actively working towards in other clinical trials.
Lumakras’ journey from “a twinkle in our eyes” to an approved product took only eight years, Amgen told Fierce Biotech last week. The FDA’s approval came months before the August action date, surprising pharmaceutical industry watchers and patients who were eagerly awaiting the decision.
“If you zoom out, the review wasn't just lightning fast, the entire program was lightning fast,” said Greg Friberg, Amgen VP and Therapeutic Area Head, Oncology, in an interview following the approval. “It's fantastic to be sitting here just under three years from the first patient being dosed and having that drug be available on the market for patients.”
Amgen intends to move fast to get the drug out to patients, too. The company had already built up a supply of product to ship out and Friberg estimates the first patients in the post-approval environment will receive doses within weeks.
“We've been moving at the fastest pace possible and the last thing we wanted was to have supply be a bottleneck. We're ready to go,” Friberg said. With the FDA approval in hand, Amgen is awaiting regulatory decisions around the world as well.
Meanwhile, at ASCO, the University of Texas MD Anderson Cancer Center’s Ferdinandos Skoulidis, M.D., Ph.D., is presenting findings from the phase 2 CodeBreaK 100 study that showed treatment with Lumakras induced a 37% objective response rate in patients and 12.5 months of median overall survival. These patients had KRAS G12C-mutated non-small cell lung cancer (NSCLC) and had previously received at least one or more rounds of treatment. Friberg said this study formed the “backbone” of the FDA application.
Skoulidis, assistant professor of Thoracic/Head & Neck Medical Oncology at MD Anderson, is thrilled that Lumakras is now approved and can be rolled out to patients, but he, like Amgen, says there’s still work to be done.
“If I were to use a boxing analogy, I would say that we have dealt KRAS a knockdown blow … [but] the fight is not over,” Skoulidis said in an interview.
Friberg estimates that with the approval in hand, the company and medical investigators like Skoulidis still “have a decade of work ahead of us” sorting through CodeBreaK and other studies involving the therapy.
“We're very early days,” Friberg said. “This is going to be a rich data set. We'll be using this data for some time to come.”
Amgen also plans to follow the patients in the trial for further long-term survival data, and Friberg hopes to see some long-term survivors coming back year after year.
The ASCO data did two things for Amgen: it began to reveal a picture of what is working and what isn’t in patients who receive the KRAS inhibitor. Or, in Friberg’s terms, what told a story and what did not tell a story. Amgen is now looking at the most granular data to ask why certain subsets of patients might have responded better, or why some did not.
“No story is a permanent negative, right? We ask the questions with the scientific method because we want to add anchor points,” Friberg said.
They found that patients with STK11 co-mutations did well on Lumakras, experiencing a 50% objective response, 11-month median progression-free survival and median overall survival of 15.3 months. Tumors with an STK11 mutation tend to have a poor response to standard-of-care therapies.
“A story is evolving here,” Friberg said. “It's important that we understand, particularly in cases where we know patients are in a very poor prognosis: Is this a drug that might be quite helpful for them and might be helpful earlier in their treatment?”
This co-mutation data is what Skoulidis found most interesting. He said the clinical activity seen in this subgroup of patients is “unprecedented and may suggest a clear avenue towards the further clinical development of sotorasib in the first-line disease setting.”
Skoulidis also pointed to a separate study to be presented at ASCO that discusses patient-reported outcomes on Lumakras, which is a once-daily oral medication. Treatment-related adverse events were mostly mild and manageable with care.
“This means that patients can enjoy an active life,” he said.
Going forward, Skoulidis wants to see more research on the molecular drivers of response to Lumakras and possible combination therapies that might prevent resistance.
Amgen has all that and more already going on in the clinic, but the data are still young. A first-line treatment trial is expected to kick off in the second half of the year.
Skoulidis and MD Anderson will continue to be involved in clinical trials for the therapy, including on the CodeBreaK 200 study that compares Lumakras with standard of care chemotherapy docetaxel. He’s also working on another clinical trial comparing the drug with other targeted therapies including checkpoint inhibitors.