Pfizer announced that the Phase 3 CROWN study of LORBRENA (lorlatinib) in people with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) met its primary endpoint by demonstrating significantly improved progression-free survival (PFS), as compared to XALKORI (crizotinib).

The results were reviewed by an independent Data Monitoring Committee (DMC) at a planned interim analysis. The safety profile for lorlatinib and crizotinib were consistent with what has been previously seen in clinical trials. The results from CROWN will be submitted for presentation at an upcoming medical congress.

“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, M.D., Ph.D., 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 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.”

In 2018, the U.S. Food and Drug Administration (FDA) approved LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication is approved under accelerated approval based on tumor response rate and duration of response. CROWN is the confirmatory study for the conversion to full approval. Based on the positive outcome of the CROWN trial, we intend to share the results with the FDA and other health authorities to support conversion to full approval and to seek approval for an indication that includes previously untreated ALK-positive metastatic NSCLC.

CROWN is a Phase 3, randomized, open-label, parallel 2-arm study in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORBRENA monotherapy or XALKORI monotherapy. The primary endpoint of the CROWN trial is PFS based on blinded independent central review (BICR). Secondary endpoints include overall survival, PFS based on investigator’s assessment, objective response (OR) based on BICR and on investigator’s assessment; intracranial OR (IC-OR), IC time to progression, duration of response (DR), IC-DR, time to tumor response (TTR), IC-TTR (all by BICR); PFS2 based on investigator’s assessment, and safety.

Lung cancer is the number one cause of cancer-related death around the world.1 NSCLC accounts for approximately 80-85% of lung cancers,2 with ALK-positive tumors occurring in about three to five percent of NSCLC cases.3 Prior to the availability of targeted therapy and immunotherapy, the five-year survival rate for patients with advanced NSCLC was just five percent.4

LORBRENA is a tyrosine kinase inhibitor (TKI) that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORBRENA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORBRENA is approved in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:

crizotinib and at least one other ALK inhibitor for metastatic disease; or

alectinib as the first ALK inhibitor therapy for metastatic disease; or

ceritinib as the first ALK inhibitor therapy for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.