Phase 3 CROWN Trial of Pfizer’s LORBRENA® (lorlatinib) Confirm Prolonged Progression-Free Survival in First-Line ALK-Positive Advanced Lung Cancer

Pfizer Inc. (NYSE: PFE) announced updated results from the Phase 3 CROWN trial, which evaluated LORBRENA® (lorlatinib, available in Europe under the brand name LORVIQUA) versus XALKORI® (crizotinib) in people with previously untreated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). This analysis reported after a median follow-up of three years, LORBRENA continued to demonstrate meaningful improvement in progression-free survival (PFS) assessed by blinded independent central review (BICR), the primary endpoint, compared to XALKORI (HR, 0.27; 95% CI, 0.18–0.39), corresponding to a 73% reduction in the rate of progression or death. These data will be presented on April 12, 2022, at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract # CT223 / 2).

“The long-term results from the CROWN trial confirm LORBRENA’s compelling safety and efficacy profile in the first-line setting, providing sustained benefit for up to three years for this patient population,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “Since its first-line approval based on the initial groundbreaking CROWN trial results, LORBRENA has solidified its place as a practice-changing medicine, and these updated data add to the growing body of evidence supporting its use from the onset of metastatic disease.”

“Approximately 25-40% of people with ALK-positive advanced non-small cell lung cancer either have brain metastases at diagnosis or develop brain metastases within two years after initial diagnosis, and biomarker-driven medicines like LORBRENA have transformed the way we treat this typically aggressive disease,” said Professor Benjamin Solomon, MBBS, Ph.D., Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia. “The new results from the CROWN trial confirm LORBRENA as a treatment option that significantly improves outcomes for people with previously untreated ALK-positive advanced NSCLC.”

In this analysis, 64% of people treated with LORBRENA were without disease progression after three years (95% CI, 55-71, n=149) compared to 19% for people treated with XALKORI after the same amount of time (95% CI, 12-27, n=147). As a secondary endpoint, the objective response rate (ORR) was 77% with LORBRENA (95% CI, 70-84) and 59% with XALKORI (95% CI, 50-67). Additionally, LORBRENA treatment resulted in a 92% reduction in the rate of intracranial progression (HR, 0.08; 95% CI, 0.04–0.17). The intracranial objective response rate (IC-ORR) for people with measurable brain metastases at baseline was 83% (95% CI, 59–96, n=15) with LORBRENA and 23% (95% CI, 5–54, n=3) with XALKORI, with an intracranial complete response rate of 72% and 8%, respectively. In people without brain metastases at baseline, LORBRENA demonstrated a 98% reduction in the rate of intracranial progression (HR 0.02; 95% CI, 0.002-0.136).

The safety profile observed in the three-year follow-up analysis was consistent with the established safety profiles of LORBRENA and XALKORI. In the initial 2020 analysis of the CROWN trial, the most frequent adverse events (AEs) in ≥20% of 149 patients treated with LORBRENA were edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea, and hypertriglyceridemia. Serious AEs occurred in 34% of people treated with LORBRENA; the most frequently reported serious AEs were pneumonia, dyspnea, respiratory failure, cognitive effects, and pyrexia. Fatal AEs occurred in 3.4% of people treated with LORBRENA. Permanent discontinuation of LORBRENA due to AEs occurred in 6.7% of people.

In the Phase 3 CROWN trial, patients were required to have an ECOG performance status of 0-2 and ALK-positive NSCLC as identified by the VENTANA ALK (D5F3) CDx assay. The primary endpoint of the CROWN trial was PFS assessed by BICR. Secondary endpoints included overall survival (OS) and time to Intracranial Progression (IC-TTP) in patients with and without baseline brain metastasis, tumor assessment related data by BICR, including ORR, duration of response (DOR) and time to treatment response (TTR). Additional secondary endpoints included PFS by investigator assessment, ORR by investigator assessment, safety, and quality of life (QOL). In patients with Central Nervous System (CNS) metastases at baseline, additional outcome measures were IC-ORR, IC-DOR and IC-TTR, by BICR. The trial is continuing to further evaluate the secondary endpoint of OS, which was not mature at the time of analysis.

About Non-Small Cell Lung Cancer (NSCLC)
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 3-5% of NSCLC cases.3 Approximately 25-40% of people with ALK-positive advanced NSCLC may develop brain metastases within two years from initial diagnosis.4

About LORBRENA® (lorlatinib)
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. by the Food and Drug Administration (FDA) for the treatment of adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test.

About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us.

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