Ignyta Announces Updated Data from Entrectinib Phase 1 Clinical Trials at the 2016 AACR Annual Meeting

SAN DIEGO -- 2016-04-17 -- Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, today announced that updated results of its Phase 1 clinical trials of entrectinib, the company's proprietary oral tyrosine kinase inhibitor targeting solid tumors harboring activating alterations to NTRK1, NTRK2, NTRK3, ROS1or ALK, were presented in an oral plenary session at the 2016 Annual Meeting of the American Association for Cancer Research (AACR) in New Orleans, Louisiana.

“We continue to be excited by entrectinib’s ability to help patients with advanced cancer,” said Jonathan Lim, M.D., Chairman and CEO of Ignyta. “With respect to efficacy, in the 25 patients in the Phase 1 trials who would meet the eligibility criteria for our Phase 2 clinical trial, we saw tumor regression in 20 patients, or 80%. 

Nineteen out of 24 patients with extracranial solid tumors had a confirmed RECIST response, representing a 79% overall response rate; and one patient with an astrocytoma had evidence of substantial tumor regression by volumetric measurement. These responses were observed in patients with each of NTRK, ROS1 and ALK rearrangements, and across six tumor histologies, including complete and/or durable responses in both primary and metastatic tumors of the central nervous system.”

“With respect to safety, based upon a larger dataset of 119 patients, which included 45 patients treated at our Phase 2 dose of 600 mg continuous once daily dosing, we have been able to further substantiate entrectinib’s acceptable safety profile,” continued Dr. Lim. “We have 19 patients who have been on study for longer than six months; of those, 11 patients have been on study for more than one year, including three patients for more than two years. We believe these data highlight the long-term tolerability and promising anti-tumor activity of entrectinib as we continue to enroll STARTRK-2, our ongoing, potentially registration-enabling Phase 2 clinical trial of entrectinib.”

The Phase 1 clinical trials included the ALKA-372-001 study and the STARTRK-1 study, which is the first of the “Studies of Tumor Alterations Responsive to Targeting Receptor Kinases”. Both trials were designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant target alterations: TrkA(encoded by NTRK1), ROS1 or ALK for ALKA-372-001 and TrkA/TrkB/TrkC(encoded by NTRK1/2/3), ROS1 or ALK for STARTRK-1.

The data cut-off for the AACR presentation was March 7, 2016. Highlights of the data included:

Safety

A total of 119 patients with a range of solid tumors had been dosed across both clinical trials, with 45 patients treated at the RP2D of 600 mg, taken orally once per day (QD).

Entrectinib was well tolerated:

• Across both studies, the most frequent (>10% incidence) treatment-related adverse events were fatigue (44%), dysgeusia (41%), paresthesia (28%), nausea (24%), and myalgia (22%).
• The vast majority of treatment-related adverse events were Grade 1 or 2 in severity.
• The most frequent (>2% incidence) Grade 3 treatment-related adverse events were fatigue (4%) and anemia (3%).
• Adverse events were reversible with dose modification.
• There was no evidence of cumulative toxicity, hepatic or renal toxicity, or QTc prolongation.

Efficacy

Across both studies, there were 25 patients treated who met the company’s Phase 2 clinical trial eligibility criteria, which include:

• Presence of NTRK1/2/3, ROS1 or ALK gene rearrangements, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);
• ALK-inhibitor and/or ROS1-inhibitor naïve; and
• Treatment at or above the RP2D.

Among the 25 patients treated who met the company’s Phase 2 clinical trial eligibility criteria, tumor regression was seen in 80% (20 out of 25 treated patients):

• 24 patients had tumors that were evaluable by RECIST criteria. The overall response rate was 79% (19 responses, including 2 complete responses, out of 24 treated patients, as assessed and confirmed by the clinical sites).
• One patient had astrocytoma. Assessment by RECIST criteria demonstrated stable disease. However, since RECIST criteria are not validated for primary brain tumors, the clinical site performed three-dimensional volumetric analysis of this patient’s tumor to determine changes in tumor size, which resulted in an estimated 45% decrease in tumor size from baseline.

Many of these responses occurred rapidly, within the first four weeks of entrectinib treatment. Seventeen of the patients remained on study treatment, having received up to 27 months of treatment. Of note, three of four patients with primary or metastatic central nervous system (CNS) disease responded.

With respect to specific subsets of patients:

Trk patients

There were four patients included in the clinical studies with NTRK1/2/3 gene rearrangements that met the company’s Phase 2 eligibility criteria, including patients with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), salivary gland cancer and astrocytoma. All four of these patients demonstrated tumor regression (three confirmed responses by RECIST and one by volumetric assessment).

Two of these Trk patients remained on study, one of whom had been on study for longer than 12 months.

In addition, the company included in the AACR presentation a case study of a 20-month old baby boy with NTRK3-rearranged infantile fibrosarcoma that had metastasized to the brain and who had exhausted all available therapies. The patient was first dosed in February 2016, and after five weeks of treatment experienced a decrease in his brain lesions of approximately 58%, as estimated from radiology assessment, with accompanying clinical improvement.

Three of these five patients with NTRK1/2/3 gene rearrangements had either primary or metastatic CNS disease, and all three demonstrated substantial CNS tumor regression, underscoring the importance of entrectinib’s CNS penetration and clinical activity for this patient population.

ROS1 patients

There were 14 patients included in the clinical studies with ROS1 gene rearrangements who met the company’s Phase 2 eligibility criteria, including 13 patients with NSCLC and one patient with malignant melanoma.

Eleven of the 13 patients with NSCLC and the patient with melanoma responded, including two complete responses. The resultant overall response rate for these ROS1 patients was 86%, and the response rate for the subset of patients with NSCLC was 85%.

Eleven of the ROS1 responders remained on study in response, with the longest at 27 months; one ROS1 NSCLC patient has met the criteria for RECIST progression but has remained on study due to clinical benefit.

ALK patients

There were seven patients included in the clinical studies with ALK gene rearrangements who met the company’s Phase 2 eligibility criteria, including four patients with NSCLC, one patient with CRC, one patient with renal cell carcinoma (RCC) and one patient with a thoracic tumor of unknown primary.

Two of the four patients with NSCLC, the patient with CRC and the patient with RCC had clinical responses. Another NSCLC patient had stable disease. The resultant overall response rate for these ALK patients was 57%.

Two of the responders remained on study in response, as did the patient with stable disease.

On Monday, April 18, 2016, Ignyta will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the entrectinib Phase 1 materials presented at the 2016 AACR annual meeting. The company’s SEC filings can be found on the company’s website at www.ignyta.com and on the SEC’s website at www.sec.gov.

Reception and Webcast Presentation

In addition, Ignyta announced that it will host a reception in New Orleans, Louisiana, on Tuesday, April 19, 2016, during the AACR annual meeting.

At the reception, Ignyta’s management team will make a presentation relating to the clinical data and plans for further development of entrectinib, as well as an overview of the company’s other product candidates and highlights.

The presentation will take place at 7:00 PM, Central time. A live webcast of the event will be available in the Investors section of the company's website at http://investor.ignyta.com, and will be archived and available at that site for 14 days.

About Ignyta, Inc.

At Ignyta, we fight cancer – a formidable opponent that manifests as thousands of different molecularly defined diseases and takes away millions of lives globally, every year. In this fight, our big hairy audacious goal (BHAG) is not just to shrink tumors but to eradicate residual disease – the source of cancer relapse and recurrence – in precisely defined patient populations by 2030. We will work tirelessly to achieve this BHAG by pursuing an integrated therapeutic (Rx) and companion diagnostic (Dx) strategy for treating cancer patients. Our Rx efforts are focused on discovering, in-licensing or acquiring, then developing and commercializing, molecularly targeted therapies that, sequentially or in combination, are foundational for eradicating residual disease. Our Dx efforts aim to pair these product candidates with biomarker-based companion diagnostics that are designed to precisely identify, at the molecular level, the patients who are most likely to benefit from the therapies we develop. We believe that only through this integrated Rx/Dx approach can we succeed in this fight. For more information, please visit: www.ignyta.com.

Forward-Looking Statements

This press release contains forward-looking statements about Ignyta as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, references to the development of Ignyta’s product candidates, references to promising signs of antitumor activity and safety and other data from the Phase 1 clinical trials of entrectinib, and potential study designs, plans and results for Phase 2 clinical trials of entrectinib. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies and operating as a development stage company; Ignyta’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in Ignyta’s plans to develop and commercialize its product candidates; the potential for final results of the ongoing clinical trials of entrectinib or other product candidates, or any future clinical trials of entrectinib or other product candidates, to differ from preliminary or expected results; Ignyta’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; Ignyta’s ability to obtain and maintain intellectual property protection for its product candidates; the risk that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained; the potential for the company to fail to maintain the CAP accreditation and CLIA certification of its diagnostic laboratory; the loss of key scientific or management personnel; competition in the industry in which Ignyta operates; and market conditions. These forward-looking statements are made as of the date of this press release, and Ignyta assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents the company files with the SEC available at www.sec.gov, including without limitation Ignyta’s Annual Report on Form 10-K for the year ended December 31, 2015 and subsequent Quarterly Reports on Form 10-Q.

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Contacts:

Ignyta, Inc.
Jacob Chacko, M.D.
CFO
858-255-5959
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Source: Ignyta, Inc.