MapKure, BeiGene and SpringWorks Announce Initiation of Phase 1 Clinical Trial of BGB-3245, a Selective Next-Generation B-RAF Inhibitor, in Adult Patients with Advanced or Refractory Solid Tumors
-- Phase 1 Study Initiated in
-- Industry-Leading Scientific Advisory Board Formed to Support Advancement of BGB-3245 --
B-RAF gene mutations and fusions have been shown to play a key role in the development of certain cancers. BGB-3245 is designed to inhibit both monomeric and dimeric forms of activating B-RAF mutations including V600 and non-V600 mutations, and RAF fusions, and has shown potent preclinical activity against a range of B-RAF gene alterations, including those for which there are no approved targeted therapies and those associated with resistance to currently approved therapies.
“Preclinical data suggest that BGB-3245 could potentially address a range of B-RAF driven tumors, which represent a significant need for patients who currently lack targeted therapeutic options, as well as patients who have developed resistance to first generation B-RAF inhibitors,” said
The Phase 1 clinical trial is a first-in-human, open-label, dose escalation and expansion study to investigate the safety, pharmacokinetics (PK) and antitumor activity of BGB-3245 in adult patients with solid tumors, including those harboring specific B-RAF driver mutations and fusions that are likely to respond to a RAF dimer inhibitor, as well as in certain adult patients who have developed resistance to first-generation B-RAF V600 inhibitors. The trial is designed to define the dose and assess the tolerability of BGB-3245 and will capture early antitumor activity signals to allow for potential cohort expansion.
In addition, MapKure has completed the formation of its
Neal Rosen, M.D., Ph.D., the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan-Kettering Cancer Center. Dr. Rosenis the founding member and Chair of the MapKure SAB. Antoni Ribas, M.D., Professor of Medicine, Professor of Surgery, and Professor of Molecular and Medical Pharmacology at the University of California Los Angeles. Kevin Koch, Ph.D., President and CEO of Edgewise Therapeutics; formerly Founder, President, and Chief Scientific Officer of Array BioPharma. Zhan Yao, Ph.D., Assistant Research Professor, Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center. Dejan Juric, M.D., Program Director, Investigational Cancer Therapeutics Program and Attending Physician in Medical Oncology, Massachusetts General Hospital.
About the Phase 1 Trial
The Phase 1 trial (NCT04249843) of BGB-3245 is an open-label, dose-escalation trial of BGB-3245 in adult patients with advanced or refractory solid tumors, including those with B-RAF driver mutations and fusions that are likely to respond to a RAF dimer inhibitor. The study will enroll patients who have experienced disease progression during or after at least one prior line of systemic anticancer therapy or for which treatment is not tolerated or acceptable to the participants.
The trial is designed in two parts: the Phase 1a portion will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose and/or the recommended Phase 2 dose and to evaluate the pharmacokinetics of BGB-3245 in patients with MAPK pathway aberrations. The Phase 1b portion will consist of one or more expansion cohorts to further evaluate the pharmacokinetics, safety, and tolerability of BGB-3245 at the recommended Phase 2 dose and to assess the preliminary antitumor activity of the compound in patients with select tumor types and B-RAF status (B-RAF point mutations and gene fusions).
BGB-3245 is an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 B-RAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer, and brain tumors. Preclinical data have demonstrated that BGB-3245 has activity in patient-derived xenografts driven by B-RAF fusions and non-V600 mutations for which approved B-RAF inhibitors are ineffective. In addition, BGB-3245’s preclinical activity in cancer models driven by V600 B-RAF mutations has suggested that it could provide an additional therapeutic option for patients with the potential to reduce dimer-driven resistance.
In addition to its intended use as a monotherapy in several genetically defined solid tumor types, BGB-3245 also has the potential to be used in rational combination therapies in the future.
MapKure is a clinical-stage company created in 2019 to develop precision medicines for patients with life-threatening diseases, with an initial focus on cancer. By focusing on genetically defined disease drivers, MapKure is positioned to advance the development of transformative medicines to patients whose unmet medical needs are largely unaddressed. MapKure is jointly owned by
SpringWorks is a clinical-stage biopharmaceutical company applying a precision medicine approach to acquiring, developing and commercializing life-changing medicines for underserved patient populations suffering from devastating rare diseases and cancer. SpringWorks has a differentiated portfolio of small molecule targeted oncology product candidates and is advancing two potentially registrational clinical trials in rare tumor types, as well as several other programs addressing highly prevalent, genetically defined cancers. SpringWorks’ strategic approach and operational excellence in clinical development have enabled it to rapidly advance its two lead product candidates into late-stage clinical trials while simultaneously entering into multiple shared-value partnerships with industry leaders to expand its portfolio. For more information, please visit www.springworkstx.com.
BeiGene Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging pre-clinical data and therapeutic potential of BGB-3245 and plans for the operations of MapKure and clinical development of BGB-3245. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including
SpringWorks Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding SpringWorks’ clinical trials and its strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, statements regarding the development of BGB-3245 or other future research and development activities conducted by MapKure, the timing for completion of SpringWorks’ clinical trials of its product candidates, whether and when, if at all, SpringWorks’ product candidates will receive approval from the
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Source: SpringWorks Therapeutics, Inc.