Xconomy National —
The treatment landscape for lung cancer has shifted significantly in recent years, and more changes would be on the way. At the World Lung Cancer Conference in Barcelona this weekend, a number of drug manufacturers showcased some of their latest advances in immunotherapy, targeted pills, drug combinations and more. Xconomy collected some of the most notable headlines and placed them in context below.
Spotlight on KRAS
In the past year, a drug called AMG 510, from Amgen (NASDAQ: AMGN) has caused quite a stir, and rightly so. It is the first drug to inhibit KRAS – a known genetic cause of multiple cancers – to not only make it into human trials, but also show evidence of an effect in cancer patients. The Amgen drug specifically targets KRAS-G12C, which has been implicated in a fraction of cancers that are extremely difficult to treat. Some Wall Street analysts have already posted multi-billion dollar revenue projections on AMG-510 following a Phase 1 update at the American Society of Clinical Oncology meeting earlier this year, where the company reported the drug showed encouraging signs in both lung and lung cancers. – as colorectal cancers without 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 has a Updating to the Phase 1 trial this weekend. The drug remained promising, but also had potential limitations. At ASCO, five out of ten lung cancer patients and the first three treated with the high-dose AMG-510 all responded, meaning their tumors have shrunk at least partially. Amgen now says that seven of the 13 patients have responded to the high dose, or 54 percent to date. Some patients who responded before have seen their cancer spread. There were still no serious side effects: Four of the 34 patients discontinued the study, but not because of AMG-510.
Taken together, those results “may be perceived as somewhat disappointing by investors,” Jefferies analyst Kennen MacKay wrote, though he added that AMG-510 appears to be superior so far to other drugs tested for lung cancer patients with KRAS G12C- mutations. The share fell more than 4 percent in premarket trading. Shares of rival Mirati Therapeutics (NASDAQ: MRTX), which has a rival KRAS-G12C inhibitor, also dropped 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 drugs, including immunotherapies.
Not long ago, 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: AZNO).
Last month, AstraZeneca said its immunotherapy durvalumab (Imfinzi) and chemotherapy alone beat chemo in a phase 3 trial, CASPIAN, in newly diagnosed patients with advanced SCLC. On Monday it delivered the details: Durvalumab/chemo reduced the risk of death by 27 percent, compared with chemotherapy alone. Patients lived an average of 13 months on the combination versus 10.3 months for chemo. About 33.9 percent of durvalumab/chemo patients lived for 18 months, compared to 24.7 percent of chemo patients. AstraZeneca is discussing the data with regulators for its own approval.
Merck (NYSE: MRK) is next, with Phase 3 data from a study of pembrolizumab (Keytruda) and chemo expected by the end of the year. They are closely monitored: Keytruda chemotherapy is already the standard of care for many patients with non-small cell lung cancer.
There is a race to develop pills to treat non-small cell lung cancer patients with RET mutations. Blueprint Medicines (NASDAQ: BPMC) has already said it plans to apply for approval next year of the pill pralsetinib, which is being tested in patients with a variety of tumors, including lung cancer, with RET mutations. On Monday, Eli Lilly (NYSE: LLY) presented results of a Phase 3 study with 531 patients, called LIBRETTO-001, testing selpercatinib. Lilly acquired the drug (formerly LOXO-292) when it bought Loxo Oncology in January for $8 billion.
The data: 68 percent of patients with RET fusion-positive NSCLC patients who received prior chemotherapy responded to selpercatinib. Those patients responded for an average of 20.3 months. Of 34 RET fusion patients who had not received chemotherapy, 85 percent responded.
SVB Leerink analyst Andrew Berens said that while response rates for Lilly’s drug were “slightly higher” than they have been with pralsetinib so far, “we don’t consider this delta to be meaningful.”
“Both drugs are likely to be clinically relevant,” he wrote in a research paper.
Lilly said it plans to file for approval for rival selpercatinib by the end of the year. The drug is also being tested in patients with medullary thyroid cancer. Shares rose 3.5 percent in premarket trading Monday. Blueprint shares fell 2.5 percent.