ARIAD Pharmaceuticals, Inc. (ARIA) today announced initiation of the Phase 1/2 clinical trial of AP32788, an investigational tyrosine kinase inhibitor (TKI) designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in EGFR or HER2. AP32788 targets tumors driven by EGFR or HER2 kinases and was designed to achieve selective inhibition of these kinases with exon 20 mutations. There are currently no approved targeted treatment options available for the approximately four to nine percent of EGFR-mutated lung tumors with exon 20 insertion mutations in NSCLC patients.1 Additionally, approximately two percent of NSCLC patients2 have HER2 mutations, with the majority having exon 20 insertion mutations.
“In the preclinical data presented at the AACR meeting last month, AP32788 demonstrated the ability to inhibit all tested EGFR and HER2 mutants, including exon 20 insertion mutants,” stated Tim Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD. “We are pleased to be advancing AP32788, the next promising cancer medicine in the ARIAD pipeline, into clinical study for patients who currently have no targeted treatment options in these orphan oncology disease subsets.”
Clinical Trial Design
The trial will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The initial Phase 1 dose-escalation trial segment will include patients with advanced NSCLC. Patients enrolled in this multicenter study will be refractory to standard available therapies. The primary objective of the Phase 1 segment of the trial is to determine the safety, tolerability, pharmacokinetic profile, and recommended Phase 2 dose (RP2D) of orally administered AP32788. ARIAD expects to enroll approximately 20 to 30 patients in this portion of the trial.
The Phase 2 expansion phase of the trial will include four histologically and molecularly defined patient cohorts, including:
- NSCLC patients with EGFR exon 20 activating insertions with no active, measurable central nervous system (CNS) metastases;
- NSCLC patients with HER2 exon 20 activating insertions or point mutations with no active, measurable CNS metastases;
- NSCLC patients with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases; and,
- NSCLC with other targets against which AP32788 has shown preclinical activity (examples include EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and other uncommon EGFR activating mutations) with or without active, measurable CNS metastases.
The Phase 2 segment of the trial is planned to enroll approximately 80 patients and will evaluate anti-tumor activity of AP32788 in these molecularly defined patient populations.
“While there are approved TKIs for use in NSCLC patients with common EGFR activating mutations, there is a need for targeted treatment options to address the subset of patients with EGFR exon 20, HER2, and other uncommon EGFR mutations,” said Robert C. Doebele, M.D., Ph.D., associate professor, division of medical oncology, University of Colorado. “This trial will evaluate the safety, tolerability and optimal dose of AP32788, and the potential activity in NSCLC patients who currently have no targeted treatment options.”
ARIAD’s Phase 1/2 clinical trial of AP32788 is expected to enroll patients at up to seven centers during the dose-escalation phase. Additional centers will be activated for enrollment of the expansion cohorts. More information about the clinical trial evaluating AP32788 can be found athttps://clinicaltrials.gov/ct2/show/NCT02716116?term=AP32788&rank=1.
EGFR mutations represent the largest known, targetable subset of NSCLC. While the most common types of EGFR mutation are addressed by approved TKI therapies, there are no targeted treatment options available for the approximately 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations. In addition, patients with HER2 mutations, mostly exon 20 insertion mutations, comprise approximately 2 percent of NSCLC patients and also have no currently approved targeted treatment options. ARIAD estimates that there are approximately 6,000 patients in the United States living with EGFR exon 20 or HER2 point mutations, based on a broader data set of 175,000 patients with stage IIIb or IV NSCLC living in the U.S. in 2015, according to Kantar Health.
AP32788 is an investigational oral tyrosine kinase inhibitor (TKI) of activating mutations in EGFR and HER2. The molecule was designed to address the unmet need in patients with non-small cell lung cancer (NSCLC) driven by exon 20 insertion mutations in EGFR and HER2, and is ARIAD’s fourth internally discovered oncology candidate to advance into clinical development.
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts is an orphan oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other difficult-to-treat orphan cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).
This press release contains forward-looking statements, each of which are qualified in their entirety by this cautionary statement. Any statements contained herein which do not describe historical facts, including, but not limited to our plans for the trial design and expected enrollment and the statements made by Drs. Clackson and Doebele, are forward-looking statements that are based on management’s expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These factors, risks and uncertainties include, but are not limited to, our ongoing strategic review, our ability to successfully commercialize and generate profits from sales of Iclusig and our product candidates, if approved; competition from alternative therapies; our ability to meet anticipated clinical trial commencement, enrollment and completion dates and regulatory filing dates for our products and product candidates and to move new development candidates into the clinic; our ability to execute on our key corporate initiatives; regulatory developments and safety issues, including difficulties or delays in obtaining regulatory and pricing and reimbursement approvals to market our products; our reliance on the performance of third-party manufacturers and specialty pharmacies for the supply and distribution of our products and product candidates; the occurrence of adverse safety events with our products and product candidates; the costs associated with our research, development, manufacturing, commercialization and other activities; the conduct, timing and results of preclinical and clinical studies of our products and product candidates, including that preclinical data and early-stage clinical data may not be replicated in later-stage clinical studies; the adequacy of our capital resources and the availability of additional funding; the ability to satisfy our contractual obligations, including under our leases, convertible debt and royalty financing agreements; patent protection and third-party intellectual property claims; litigation; our operations in foreign countries; risks related to key employees, markets, economic conditions, health care reform, prices and reimbursement rates; and other risk factors detailed in our public filings with the U.S. Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.
1 Costa, D. 2015. EGFR Exon 20 Insertion in Non-Small Cell Lung Cancer. My Cancer Genomehttp://www.mycancergenome.org/content/disease/lung-cancer/egfr/64/ (Updated November 5, 2015).
2 JCO April 22, 2013 JCO.2012.45.6095