cancer September 10, 2015 | By John Carroll AstraZeneca ($AZN) may still be in front in the late-stage race to develop a targeted new drug for non-small cell lung cancer, but new data has analysts wondering if its lead over rival Clovis ($CLVS) has shortened in the final stretch. The pharma giant says that AZD9291, one of its top cancer prospects, demonstrated median progression free survival of 8.6 months in a mid-stage study of previously treated patients with the EGFR T790M mutation. By itself, that was a positive outcome, but nothing that AstraZeneca does here plays out in a vacuum. The result--based on preliminary data that could yet change--fell short of the advantage that some analysts were looking for to keep competition from Clovis's rociletinib (CO-1686) at bay. And it was uncomfortably close to the 8-month PFS rate that Clovis had to explain for the same patients at the latest ASCO gathering in Chicago. Advantage, Clovis, which saw its shares shoot up 14% on Wednesday, with a fresh bump Thursday morning. "Heading into WCLC, feedback from MEDACorp key opinion leaders (KOLs) was that if AZD9291 maintained its 3-month PFS advantage over rociletinib as highlighted at ECLC and ASCO they would use AZD9291 in 80-90% of T790m + patients," noted Leerink's Seamus Fernandez. "With these data, most KOLs still prefer AZD9291, but the impact frequency of rash with AZD9291 vs. diabetes with rociletinib suggests that AZD9291 may not dominate the market to the degree previously assumed." AstraZeneca may be far, far bigger than Clovis, but it has just as much to prove as the biotech. AZD9291 and its close-watched PD-L1 program are central to the pharma giant's case that it is on the comeback trail after years in the industry dog house. And Clovis is also advancing rucaparib, a rival to AstraZeneca's newly-approved Lynparza. The race, though, is far from finished. And analysts will be judging every new data set that comes through.
Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer
N Engl J Med 2015; 372:1700-1709April 30, 2015DOI: 10.1056/NEJMoa1413654
BACKGROUND Non–small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M.
METHODS In this phase 1–2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles.
RESULTS A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51).
CONCLUSIONS Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; ClinicalTrials.gov number, NCT01526928.)
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