Approval based on results from Phase 3 CROWN trial, showing LORVIQUA reduced risk of disease progression or death by 72% in newly diagnosed individuals compared to XALKORI® (crizotinib)

NEW YORK, NY, USA I January 28, 2022 I Pfizer Inc. (NYSE: PFE) announced today that the European Commission (EC) granted marketing authorization for LORVIQUA® (lorlatinib, available in the U.S. under the brand name LORBRENA®) as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)- positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.

“For more than a decade, Pfizer has worked tirelessly in its pursuit to help transform the trajectory for people living with advanced, biomarker-driven lung cancers,” said Andy Schmeltz, Global President & General Manager, Pfizer Oncology. “The European Commission’s approval of LORVIQUA as a first-line therapy is a significant milestone that we hope will help bring a needed and meaningful difference to those impacted by this deadly disease in Europe.”

The approval for the first-line use of LORVIQUA was based on the results of the pivotal Phase 3 CROWN trial, in which LORVIQUA reduced the risk of disease progression or death by 72% compared to XALKORI® (crizotinib). As a secondary endpoint, the confirmed objective response rate (ORR) was 76% (95% CI, 68 to 83) with LORVIQUA and 58% (95% CI, 49 to 66) with XALKORI. In patients with measurable brain metastases, 82% of patients in the LORVIQUA arm experienced an intracranial response (71% had an intracranial complete response), compared to 23% of XALKORI patients. The CROWN trial is a randomized, open-label, parallel 2-arm trial in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORVIQUA monotherapy (n=149) or XALKORI monotherapy (n=147).

“The expanded approval for LORVIQUA in Europe is a considerable advancement – especially for the close to 40 percent of patients with ALK-positive metastatic NSCLC who are faced with brain metastases at diagnosis,” said Professor Benjamin Solomon, MBBS, PhD., Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia. “It is exciting to see the significant data generated from the CROWN trial continuing to support expanded use around the world and providing physicians in Europe with a highly effective option from the onset of their patients’ treatment journey.”

The EC approval of LORVIQUA follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in December 2021. LORVIQUA is approved in the U.S. by the Food and Drug Administration (FDA) under the brand name LORBRENA for the treatment of adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. In 2019, the EC granted conditional marketing authorization for LORVIQUA as a monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI.

About the CROWN Trial of LORVIQUA

In the 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 progression-free survival (PFS) based on blinded independent central review (BICR). Secondary endpoints included overall survival (OS) and tumor assessment related data by BICR, including ORR, and duration of response (DOR). In patients with measurable central nervous system (CNS) metastases at baseline, additional outcome measures were intracranial (IC)-ORR and IC-DOR by BICR. The trial is continuing in order to further evaluate the secondary endpoint of OS, which was not mature at the time of analysis.

Overall, the safety profile of LORVIQUA was similar to that reported in previous studies. The most frequent adverse events (AEs) in ≥20% of 149 patients treated with LORVIQUA were edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea and hypertriglyceridemia. Serious AEs occurred in 34% of people treated with LORVIQUA; 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 LORVIQUA. Permanent discontinuation of LORVIQUA due to AEs occurred in 6.7% of people. Detailed results from the CROWN study were published in the November 2020 issue of the New England Journal of Medicine.

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 Up to 40% of people with ALK-positive metastatic NSCLC present with brain metastases at initial diagnosis.4,5,6

About LORVIQUA® (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.

The full U.S. prescribing information for LORBRENA can be found here.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.

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. We routinely post information that may be important to investors on our website at In addition, to learn more, please visit us on and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at

1 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2020: Lung fact sheet. Accessed January 2022.
2 American Cancer Society. What is lung cancer? Accessed January 2022.
3 Garber K. ALK, lung cancer, and personalized therapy: portent of the future? J Natl Cancer Inst. 2010;102:672-675.
4 Peters S. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. 2017;377:829-38​.
5 Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALKrearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389:917–929.
6 Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer. JCO Precis Oncol. 2017;2017.

SOURCE: Pfizer