Pfizer Inc. announced that the US Food and Drug Administration (FDA) has approved Xalkori (crizotinib) capsules, the first-ever therapy targeting anaplastic lymphoma kinase (ALK), for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by an FDA-approved test. The effectiveness of Xalkori is based on objective response rates (ORR) and, as Xalkori received accelerated approval from the FDA, Pfizer is conducting post-marketing clinical trials to further evaluate its clinical benefit.

“Overall, lung cancer is responsible for more deaths each year worldwide than any other type of cancer. Xalkori is an advance in the treatment of this devastating illness, providing a new therapeutic option for a subset of patients with the disease,” said Ian Read, president and chief executive officer of Pfizer. “The acceleration, collaboration and critical focus of the Xalkori clinical development program reflect Pfizer’s Precision Medicine approach to advancing our pipeline and strengthening our innovative core to deliver medicines that matter most.”

Aligned with the FDA’s latest guidance on targeted therapies and companion diagnostics, the Company worked closely with the FDA and partnered with Abbott Molecular’s business in Pfizer’s clinical studies to ensure the simultaneous review and approval of Xalkori along with a diagnostic test, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit, to identify presence of the ALK fusion gene. The simultaneous approval of Xalkori in parallel with Abbott Molecular’s ALK FISH Test marks the first time a Pfizer oncology drug or any lung cancer medication was developed and approved in parallel with a diagnostic test.

“By truly understanding the underlying genetic drivers of NSCLC, such as ALK, we can select patients who are more likely to respond to treatment. Xalkori provides a model for how to approach future drug development and cancer care,” said Dr. Paul Bunn, professor of medicine and the James Dudley chair in cancer research at the University of Colorado, Denver. “Xalkori, the first new drug approved for lung cancer by the FDA in more than six years, represents a paradigm shift in NSCLC treatment, where we’re moving away from a one-size-fits-all approach to biomarker-based treatment decisions.”

In the clinical trials for Xalkori, the study design required patients’ tumours to prospectively test positive for the ALK fusion gene biomarker, increasing the likelihood of response to the treatment. This method, a first for a lung cancer therapy not yet on the market, allowed researchers to observe a strong efficacy signal in a selected patient population. Preliminary epidemiology suggests that approximately 3-5 per cent of NSCLC tumours are ALK-positive, translating to approximately 6,500 to 11,000 NSCLC patients in the US each year.

“Xalkori represents a new chapter in personalized therapy for lung cancer, enabling physicians to provide the right treatment for the right patient,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit. “The development of Xalkori – from publication of the discovery of the ALK fusion gene in NSCLC to FDA approval in just four years - is a remarkable feat in the oncology world and reinforces the importance of collaboration among academic research, pharmaceutical, diagnostic and regulatory organizations.”

Using a targeted approach in the Xalkori registration trials, ORR of 50 and 61 per cent were observed in patients with advanced ALK-positive NSCLC.1

“Today’s approval of Xalkori underscores the important role of molecular biomarkers in cancer treatment,” said Dr. Joan Schiller, president of National Lung Cancer Partnership and chief of Haematology/Oncology, University of Texas Southwestern Medical Center. “We strongly encourage lung cancer patients to talk to their oncologists about molecular tumour testing. By having a full understanding of the molecular biology of their tumor, patients and physicians can make well-informed treatment decisions.”

New Drug Applications for crizotinib have also been filed by Pfizer with the Japanese Ministry of Health, Labour and Welfare, the Korean Ministry of Health, the European Medicines Agency and the Swiss Agency for Therapeutic Products.

The FDA approval of Xalkori is based on data from 255 patients with locally advanced or metastatic ALK-positive NSCLC across 2 multi-center, single-arm studies, including a Phase 2 study (PROFILE 1005) and a Part 2 expansion cohort of a Phase 1 study (Study 1001).1 The primary efficacy endpoint in both studies was Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST). Response was evaluated by the investigator. Duration of Response (DR) was also evaluated.1

In PROFILE 1005 (n=136), based on investigator assessments, the ORR was 50 per cent, including one complete response and 67 partial responses.1 The median duration of treatment was 22 weeks. Seventy-nine per cent of objective tumour responses were achieved during the first 8 weeks of treatment. The median response duration was 41.9 weeks.

In Study 1001 (n=119), based on investigator assessments, the ORR was 61 per cent, including two complete responses and 69 partial responses. The median duration of treatment was 32 weeks. Fifty-five percent of objective tumour responses were achieved during the first 8 weeks of treatment. The median response duration was 48.1 weeks.

As part of its post-marketing requirements, Pfizer continues to evaluate Xalkori in confirmatory, randomized, open-label phase 3 trials. PROFILE 1007 compares the efficacy and safety of Xalkori with standard of care chemotherapy (pemetrexed or docetaxel) in patients with previously treated advanced ALK-positive NSCLC. Profile 1014 compares the efficacy and safety of XALKORI to pemetrexed/cisplatin or pemetrexed/carboplatin in previously untreated patients with advanced ALK-positive non-squamous NSCLC.

Xalkori is a kinase inhibitor indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. This indication is based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with Xalkori. Xalkori blocks signalling in a number of cell pathways that are believed to be critical for the growth and survival of tumour cells, which may lead to stabilization or regression of tumors. Alterations in the ALK gene are believed to be a key driver of tumour development in cancers like NSCLC. Although ALK is known to occur more frequently in patients with non-squamous cell carcinoma and histories of light or non-smoking, it has also been identified in smokers and in patients with squamous cell carcinoma histologies.20 Alterations in the ALK gene can occur independent of age, gender, ethnicity and smoking history.

Xalkori has also demonstrated inhibition of the c-MET receptor tyrosine kinase and is under investigation.