Results from dozens of major cancer drug clinical trials were reported over the weekend, as the European Society of Medical Oncology's annual conference took place online.
Many of those studies were run by large pharmaceutical companies like Merck & Co. and Bristol Myers Squibb, as more and more of the industry emphasizes its oncology research. But one of the most notable datasets came from Mirati Therapeutics, a California biotech with a few hundred employees that's proving a once-undruggable target now isn't.
AstraZeneca and partner Daiichi Sankyo, meanwhile, could lay claim to the next milestone in breast cancer treatment.
Here are three of the highest impact datasets from the fall's most important cancer research meeting, along with an additional update from outside the conference that arrived Monday:
Mirati steps ahead of Amgen with colon cancer data
In May, Amgen won Food and Drug Administration approval for the first drug that can target KRAS, a oft-mutated gene in lung, colon and pancreatic cancers that's stymied researchers for four decades. A handful of rival drugmakers have already lined up behind Amgen in hopes of repeating the biotech's breakthrough.
Over the weekend at ESMO, and again on Monday, Mirati, the most advanced of the bunch, revealed new data suggesting its experimental KRAS-blocking candidate could improve on Amgen's Lumakras, at least in colon cancer. (Lumakras is approved in lung cancer, but not in colon cancer.)
Results from an early study showed Mirati's drug, called adagrasib, helped to shrink tumors in 10 out of 45 patients with advanced colon cancer positive for the specific kind of KRAS mutations it targets. Pairing adagrasib with Eli Lilly's Erbitux led to a treatment response rate of 43%, or nearly double what was reported with monotherapy.
Both marks are notably higher than the 10% and 27% response rates Amgen has reported for Lumakras monotherapy and Lumakras together with another drug called Vectibix, although comparisons across clinical trials can be misleading. Treatment with adagrasib was associated with some notable side effects, however, including increases in liver enzyme counts and an abnormal heart rhythm in a handful of study participants.
Whether Mirati's drug actually represents an improvement on Amgen's in treating colon cancer will require more data, which the former company is collecting in ongoing and planned clinical trials. Still, Mirati's data appeared well received by investors Monday, who pushed shares in the biotech company up by nearly 5%.
It's in advanced lung cancer, however, that Mirati will first attempt to challenge Amgen. New data unveiled Monday showed adagrasib led to a response rate of 43% in the Phase 2 study the company plans to use to support an FDA approval application set to be filed later this year.
Guiding submission of that application, and commercialization of adagrasib should an approval follow, will be a new CEO. On Monday, Mirati announced that David Meek, the former head of FerGene and Ipsen, will join as chief executive, effective immediately.
A new standard in HER2 breast cancer?
Typically, when cancer physicians and researchers evaluate clinical trial results for a new drug, they look for data showing at least a 20% reduction in risk versus existing therapy on measures like time to disease progression, or an ability to extend survival.
On Saturday, AstraZeneca and Daiichi Sankyo reported that treatment with their breast cancer therapy Enhertu cut the risk of disease progression or death by a remarkable 72% versus Roche's Kadcyla in previously treated patients.
The companies were studying Enhertu in people with breast cancer positive for a protein known as HER2, the target of Kadcyla and other standard drugs like Perjeta and Herceptin. With their results, Enhertu could soon become a new go-to treatment for second-line breast cancer.
AstraZeneca and Daiichi Sankyo's study, called DESTINY-Breast03, enrolled just over 500 patients, randomizing them to receive either Enhertu or Kadcyla. Measured by investigators, the median progression-free survival among those given Enhertu was roughly 25 months, three times longer than the 7 months reported for those who got Kadcyla.
The study hasn't gone on long enough to be sure, but the early data available suggest Enhertu extends patients' lives for longer than Kadcyla, too.
On safety, the companies said no new safety concerns with Enhertu were reported, although they noted that treatment was associated with low immune cell and platelet counts. Two severe cases of interstitial lung disease were also observed by investigators.
For AstraZeneca, the data is welcome validation for the large bet the company placed on Enhertu in a $6.9 billion licensing agreement with Daiichi Sankyo two and half years ago. The deal was championed at AstraZeneca by the late José Baselga, who joined the British pharma from Memorial Sloan Kettering Cancer Center in 2019.
Strengthening data from Keytruda rivals
Seven cancer immunotherapies approved in the U.S. work by blocking proteins known as PD-1 or PD-L1. An eighth, from Beigene and Novartis, is now under review.
The lion's share of the market, however, is controlled by only one: Merck's Keytruda, which earned the drugmaker nearly $7 billion in sales through the first six months of 2021.
Merck's rivals, both those already on market and those still advancing through clinical development, are working to challenge Keytruda's dominance.
At ESMO, two groups — partners Regeneron and Sanofi as well as EQRx and CStone Pharmaceuticals — unveiled new data that could help their quest.
In Regeneron and Sanofi's study, patients with a type of metastatic lung cancer who received the companies' drug, Libtayo, together with chemotherapy lived a median of 9 months longer than those on chemo alone — a relative risk reduction of 29%.
Yet the results, while positive, may not be enough to unseat Keytruda, according to at least one group of analysts.
"We believe Libtayo’s performance could enable it to compete for share with Opdivo in the [first-line non-small cell lung cancer] setting; however, we believe it will be challenging to compete with Keytruda's entrenched status, particularly in the U.S.," wrote SVB Leerink's Geoffrey Porges, referring to Bristol Myers Squibb's PD1-inhibitor in a Sept. 20 note to clients.
EQRx and CStone, meanwhile, are still gathering evidence to support an application for FDA approval for their experimental anti-PD-1 drug sugemalimab. Results at ESMO, from a study in locally advanced or unresectable Stage 3 lung cancer, showed treatment reduced the risk of disease progression or death by 36% versus placebo.
The data follow positive results from another study in first-line metastatic non-small cell lung cancer at the World Conference on Lung Cancer last week.
Bonus: An FDA decision date is set for Bristol Myers' next immmunotherapy
Bristol Myers headlined the year's other big cancer research meeting — the American Society of Clinical Oncology's virtual conference — with data showing a new kind of immunotherapy could help keep aggressive skin cancer at bay. The drug, called relatlimab and targeting a protein known as LAG-3, represents another way of training the immune system to go after tumors.
While the pharmaceutical company only had a small update to share at ESMO, there was bigger news on the regulatory front. The FDA, Bristol Myers said, agreed to evaluate its approval application with a speedy review, setting a target decision date of March 19, 2022.
Correction: A previous version of this story misidentified the drug AstraZeneca and Daiichi Sankyo used as a comparator in their DESTINY-Breast03 study. The study compared Enhertu to Kadcyla, not Perjeta.