Results from a phase 3 study of Pfizer’s third-generation ALK inhibitor Lorbrena have come back positive as the pharma company builds its case for an extension into the early lung cancer treatment setting.
Lorbrena (lorlatinib) is being evaluated in patients with previously untreated ALK-positive non-small cell lung cancer – participants were randomised to receive either Lorbrena monotherapy or Pfizer’s first-generation ALK-inhibitor Xalkori (crizotinib).
At the planned interim analysis, Lorbrena came out on top, demonstrating a significantly improved progression-free survival rate compared to Xalkori. The safety profile for both therapies was consistent with what has previously been observed in clinical trials.
Currently, Lorbrena is approved only in the second-line setting, for patients who have already been treated with one or more therapies, including Xalkori and treatments from a slew of competitors.
Sales of Xalkori have come under pressure recently as it faces increasing pressure from Roche’s Alecensa (alectinib) and Novartis’ Zykadia (ceritinib), with both therapies having previously bested Pfizer’s first-generation ALK inhibitor in head-to-head trials.
Although Lorbrena will face extreme competition from Alecensa and Zykadia, an entry into the first-line market will most likely help Pfizer to reclaim some the losses resulting from Xalkori’s decline.
Despite the NSCLC market being largely dominated by Merck & Co’s Keytruda (pembrolizumab), the ALK-positive patient group is an important subset, with this type of tumour mutation occurring in around 3-5% of cases.
Follow-up ALK inhibitors are particularly crucial in this treatment setting, given that many patients experience tumour progression after initial treatment and often require a second- or third-line option.
Pfizer has not yet revealed the detailed results from the phase 3 Lorbrena study, but said that the full data is due to be presented at an upcoming medical congress. The company added that it also intends to share the results from the study with the US Food and Drug Administration (FDA) and other health regulators across the globe to support its approval ambitions.
“Almost a decade ago, we pioneered the first biomarker-driven medicine for ALK-positive non-small cell lung cancer, which transformed treatment of this disease,” said Chris Boshoff, chief development officer, Oncology, Pfizer Global Product Development.
“These top-line results of the CROWN study reinforce the significant benefit of Lorbrena demonstrated in later-line settings, and we are excited to share this data soon with physicians and other healthcare providers, as well as engage with global regulatory authorities to potentially provide this third-generation ALK-inhibitor to people with previously untreated metastatic non-small cell lung cancer,” he added.