“Pfizer Inc. (NYSE:PFE) today announced full results from the Phase 2 clinical trial of the investigational, next-generation tyrosine kinase inhibitor lorlatinib that exhibited clinically meaningful activity against lung tumors and brain metastases in a range of patients with ALK-positive and ROS1-positive advanced non-small cell lung cancer (NSCLC), including those who were heavily pretreated. Further, side effects were generally manageable and primarily mild to moderate in severity. The results [Abstract #OA 05.06] were presented by Professor Benjamin Solomon, lead investigator and medical oncologist at Peter MacCallum Cancer Centre, Melbourne, Australia, today during an oral session at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan. Pfizer will also present data from several other lung cancer clinical programs.”
“Ceritinib appeared safe and effective in patients with ROS1–rearranged non–small cell lung cancer, according to a multicenter, open-label phase 2 study.
“ALK inhibitors — especially crizotinib (Xalkori, Pfizer) — effectively treat ROS1–positive cell lines and tumors. However, patients eventually develop resistance and experience a high incidence of brain recurrence.
” ‘Treatment options beyond crizotinib are needed, and clinical development of other ROS1 inhibitors should be accelerated to improve treatment outcome of patients with ROS1–positive NSCLC,’ Byoung Chul Cho, MD, PhD, assistant professor at Yonsei Cancer Center of Yonsei University College of Medicine, and colleagues wrote.”
“Pfizer Inc. (NYSE:PFE) today announced encouraging new data from a Phase 1/2 study of lorlatinib, the proposed generic name for PF-06463922, Pfizer’s investigational, next-generation ALK/ROS1 tyrosine kinase inhibitor. The study showed clinical response in patients with ALK-positive or ROS1-positive advanced non-small cell lung cancer (NSCLC), including patients with brain metastases. These data were presented today in an oral presentation at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“The results presented are from the dose escalation component of an ongoing Phase 1 study of patients with ALK-positive or ROS1-positive NSCLC, with or without brain metastases, who were treatment-naïve or had disease progression after at least one prior tyrosine kinase inhibitor (TKI). Among patients with ALK-positive metastatic NSCLC, the overall response rate (ORR) with lorlatinib was 46 percent, with three patients achieving complete responses and 16 patients achieving a partial response (95% CI: 31-63). The median progression free survival (PFS) was 11.4 months (95% CI: 3.4 – 16.6). The majority of patients had received two or more prior ALK TKIs. Additionally, lorlatinib showed the ability to decrease the size of brain metastases in patients with ALK-positive or ROS1-positive metastatic NSCLC.”
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“The FDA granted priority review to a supplemental new drug application for crizotinib.
“Crizotinib (Xalkori, Pfizer) — a kinase inhibitor — already is approved for treatment of patients with metastatic ALK-positive non–small cell lung cancer.
“The supplemental application requests that the approval be expanded to allow crizotinib to be used for treatment of patients with metastatic ROS1-positive NSCLC. The FDA granted breakthrough therapy designation to crizotinib for this indication in April.
“ROS1 rearrangement occurs in an estimated 1% of NSCLC cases, according to a Pfizer-issued press release.”
“The FDA has granted a priority review for a supplemental new drug application (sNDA) for crizotinib (Xalkori). The application is for an indication in patients with metastatic non–small cell lung cancer (NSCLC), whose tumors are ROS1-positive, according to a press release posted by Pfizer Inc.
” ‘ROS1 is another gene rearrangement. It is like ALK in that it is structurally related, but rarer. ROS1 occurs in about 1% of [NSCLC] patients, but [it has] also been seen in other types of rare cancers,’ said D. Ross Camidge, MD, PhD, director, Thoracic Oncology Clinical Program, University of Colorado Cancer Center, in an interview with Targeted Oncology. He added that crizotinib, originally an ALK inhibitor, may be even more effective as a ROS1 inhibitor. ‘It’s great for that small population of patients.’ “
“Ignyta, Inc. (Nasdaq: RXDX),a precision oncology biotechnology company, today announced a clinical collaboration with the University of California, San Francisco (UCSF), under which UCSF will study entrectinib in a proof-of-concept clinical trial in cancer patients with metastatic melanoma that is positive for activating alterations to NTRK1/2/3 (encoding TrkA/TrkB/TrkC) or ROS1.
“ ‘We are excited to collaborate with UCSF, a world-renowned academic research institution,’ said Jonathan Lim, M.D., Chairman and CEO of Ignyta. ‘The focus on melanoma in this study will complement the broader range of indications on which we are focused in our own clinical trials, and we expect the findings to accelerate our understanding of the potential role of entrectinib in treating patients with NTRK-positive and ROS1-positive cancers.’
“Under the terms of the collaboration agreement, Ignyta will contribute $1 million toward the funding of the clinical trial, as well as per-patient fees based on enrollment of NTRK-positive or ROS1-positive patients and their participation in the trial. Ignyta will also provide UCSF with sufficient supply of entrectinib for use in the clinical trial. In addition to the safety and efficacy data from the trial, UCSF will provide Ignyta with tumor samples and genetic sequencing data for patients screened for inclusion in the trial for further genomic analysis.”
“Pfizer Inc. announced today that XALKORI® (crizotinib) received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of patients with ROS1-positive non-small cell lung cancer (NSCLC). Occurring in approximately one percent of NSCLC cases1, ROS1-positive NSCLC represents a particular molecular subgroup of NSCLC.2 XALKORI currently is approved in the U.S. for the treatment of patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.
“Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is “intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.”3The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.4
“ ‘We are excited that the FDA has granted Breakthrough Therapy designation for XALKORI as a potential treatment for patients with ROS1-positive NSCLC,’ said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. ‘XALKORI pioneered precision medicine for ALK-positive metastatic NSCLC, and ROS1 represents a second molecular subgroup of NSCLC in which XALKORI has demonstrated a level of anti-tumor activity that can potentially make a real difference for patients.’ ”