Pfizer Inc.’s phase 3 CROWN trial examining lorlatinib to treat patients with ALK-positive NSCLC met its primary end point of improving progression-free survival when compared to crizotinib.
The phase 3 CROWN study, designed to examine lorlatinib (Lorbrena) for previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), met its primary end point of improving progression-free survival (PFS) when compared to crizotinib (Xalkori), according to a Pfizer Inc. press release.
An independent Data Monitoring Committee reviewed the results at a planned interim analysis. More, the safety profiles for lorlatinib and crizotinib were consistent with the data found in previous clinical trials.
“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,” Chris Boshoff, MD, PhD, chief development officer for Pfizer Global Product Development, said in a press release.
Lorlatinib was previously granted accelerated approved by the FDA in 2018 to treat patients with ALK-positive metastatic NSCLC whose disease progressed on crizotinib and another ALK inhibitor for metastatic disease; or progression of disease on alectinib (Alecensa) or ceritinib (Zykadia) as the first ALK inhibitor therapy. The approval was based on tumor response rate and duration of response.
The CROWN trial is the confirmatory study to convert the accelerated approval into a full approval from the FDA. The trial is also critical for Pfizer Inc. to seek approval for an indication including previously untreated ALK-positive metastatic NSCLC.
“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 these data soon with physicians and other healthcare providers, as well as engage with global regulatory authorities to potentially provide people with previously untreated metastatic non-small cell lung cancer this third-generation ALK-inhibitor,” said Boshoff.
The CROWN trial is a phase 3, randomized, open-label, parallel 2-arm study. The main cohort randomized 296 patients with previously untreated advanced ALK-positive NSCLC 1:1 to receive either lorlatinib monotherapy or crizotinib monotherapy.
The study’s primary end point is PFS based on blinded independent review. Some of the secondary end points include overall survival, PFS based on investigator’s assessment, objective response (OR) based on blinded independent review, intracranial OR, and safety among other things.
Results from the CROWN trial will be submitted for presentation at a later date for an upcoming medical congress.
Around the world, lung cancer is the most common cause of cancer-related deaths. Specifically, NSCLC accounts for 80-85% of lung cancer diagnoses, with ALK-positive tumors appearing in 3-5% of those cases. The 5-year survival rate for patients with advanced NSCLC was 5% before the introduction of targeted therapy and immunotherapy.
LORBRENA® (LORLATINIB) SIGNIFICANTLY IMPROVES PROGRESSION-FREE SURVIVAL IN FIRST-LINE ALK-POSITIVE LUNG CANCER [news release]. New York, New York. Published August 5, 2020. https://www.pfizer.com/news/press-release/press-release-detail/lorbrenar-lorlatinib-significantly-improves-progression. Accessed August 5, 2020.