The treatment landscape for lung cancer has shifted significantly over the past few years, and more changes could be on the way. At the World Conference on Lung Cancer in Barcelona this weekend a number of drug makers trotted out some of their latest advances in immunotherapy, targeted pills, drug combinations, and more. Xconomy rounded up some of the most noteworthy headlines and put them in context below.
Spotlight on KRAS
Over the past year, a drug called AMG 510, from Amgen (NASDAQ: AMGN) has caused quite a stir, and for good reason. It’s the first drug to inhibit KRAS—a known genetic driver of multiple cancers—to not only make it into human testing, but also to show evidence of an effect in cancer patients. The Amgen drug specifically targets KRAS-G12C, which is implicated in a fraction of cancers that are extremely difficult to treat. Some Wall Street analysts have already placed multi-billion dollar revenue projections on AMG-510 following a Phase 1 update at the American Society of Clinical Oncology’s meeting earlier this year, where the company reported that the drug showed encouraging signs in both lung and colorectal cancers without any serious side effects. About 13 percent of patients with non-small cell lung cancer, the most common form of lung cancer, have a KRAS-G12C mutation.
Amgen provided an update to the Phase 1 study this weekend. The drug continued to show promise, but potential limitations as well. At ASCO, five of 10 lung cancer patients and the first three who had been treated on the high dose of AMG-510 all responded, meaning their tumors at least partially shrunk. Amgen now says seven of 13 patients on the high dose, or 54 percent thus far, have responded. Some patients who previously responded have seen their cancer spread. There were still no serious side effects: four of 34 total patients have dropped out of the study, but not because AMG-510.
All told, those results “may be perceived as somewhat disappointing by investors,” wrote Jefferies analyst Kennen MacKay, though he added that AMG-510 so far seems superior to other drugs tested for lung cancer patients with KRAS G12C mutations. Shares fell more than 4 percent in pre-market trading. Shares of rival Mirati Therapeutics (NASDAQ: MRTX), which has a rival KRAS-G12C inhibitor, also slumped 6 percent.
Amgen will present more data at a medical meeting in Europe later this month and is testing the drug in combination with other medicines, among them immunotherapies.
It wasn’t too long ago that chemotherapy was the only option for small cell lung cancer, an aggressive form of the disease linked to smoking. But immunotherapy has changed that: the FDA approved a combination of chemotherapy and the Roche immunotherapy atezolizumab (Tecentriq) in March. Other combinations are on Roche’s heels, and the first challenger comes from AstraZeneca (NYSE: AZN).
Last month, AstraZeneca said its immunotherapy durvalumab (Imfinzi) and chemotherapy beat chemo alone in a Phase 3 study, CASPIAN, in newly diagnosed patients with advanced SCLC. On Monday, it provided the details: Durvalumab/chemo cut the risk of death by 27 percent, compared to chemo alone. Patients lived a median of 13 months on the combination versus 10.3 months for chemo. Some 33.9 percent of durvalumab/chemo patients were alive 18 months, versus 24.7 percent of chemo patients. AstraZeneca is discussing the data with regulators, aiming for an approval of its own.
Merck (NYSE: MRK) is up next, with Phase 3 data from a study of pembrolizumab (Keytruda) and chemo expected by the end of the year. They’ll be closely watched: Keytruda-chemo is already the standard of care for many patients with non-small cell lung cancer.
A competitive race is on to develop pills to treat non-small cell lung cancer patients with RET mutations. Blueprint Medicines (NASDAQ: BPMC) has already said it plans to file for approval next year of pill pralsetinib, which is being tested in patients with a variety of tumors, among them lung cancer, with RET mutations. On Monday, Eli Lilly (NYSE: LLY) presented results from a 531-patient Phase 3 study called LIBRETTO-001 testing selpercatinib. Lilly acquired the drug (formerly called LOXO-292) when it bought Loxo Oncology for $8 billion in January.
The data: 68 percent of patients with RET fusion-positive NSCLC patients who previously got chemotherapy responded to selpercatinib. Those patients responded for a median of 20.3 months. Of 34 RET fusion patients who hadn’t gotten chemotherapy, 85 percent responded.
SVB Leerink analyst Andrew Berens said that while the response rates for Lilly’s drug were “slightly higher” than those seen thus far with pralsetinib, “we do not see this delta as meaningful.”
“Both drugs are likely to be clinically relevant,” he wrote in a research note.
Lilly said it aims to file for approval of rival selpercatinib by the end of the year. The drug is also being tested in patients with medullary thyroid cancer. Shares climbed 3.5 percent in pre-market trading Monday. Blueprint shares ticked down 2.5 percent.