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Jounce Therapeutics Presents Data Highlighting Advances From Two Programs in its Immuno-Oncology Pipeline at the 2016 AACR Annual Meeting

On April 17, 2016 Jounce Therapeutics, Inc., a company focused on the discovery and development of novel cancer immunotherapies coupled to patient enrichment strategies,reported that they have presented new preclinical data from two programs in the company’s immuno-oncology pipeline at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans (Press release, Jounce Therapeutics, APR 17, 2016, View Source [SID:1234511009]). The data presented represent the broad applicability of Jounce’s Translational Science Platform.

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ICOS Program
Jounce’s first presentation highlighted JTX-2011, a humanized ICOS (inducible costimulator molecule) agonist antibody being developed for the treatment of solid tumors. JTX-2011 has a dual mechanism of action, stimulating T effector cells and selectively reducing intra-tumoral T regulatory cells, thereby shifting the balance of T cells in a tumor toward anti-tumor activity. JTX-2011 has demonstrated durable anti-tumor efficacy in multiple preclinical tumor models as both a single agent and in combination with anti-PD-1 therapy. Today’s presentation provides preclinical data on JTX-2011, including evaluation of JTX-2011 in non-human primates, in which the antibody was shown to be well tolerated.

Jounce plans to file an investigational new drug application for JTX-2011 in mid-2016 and commence clinical trials evaluating JTX-2011 both as a monotherapy cancer immunotherapeutic and in combination with other immunotherapies for solid tumors in the second half of 2016.

Beyond T Cell Program
Beyond the JTX-2011 lead program, Jounce has utilized its Translational Science Platform to characterize the immune cell type infiltrate in human tumors in a large scale analysis. Using an immune cell type signature approach, tumors are characterized by the prevalence of a particular immune cell type, facilitating relevant target prioritization of that cell type and coordinated biomarker identification of those tumors. Jounce is applying this strategy to multiple immune cell types, including immuno-suppressive macrophages.

Today’s presentation demonstrates that TIM-3 and LILRB2, a novel protein-to-protein binding pair on human macrophages, discovered through this platform, may provide a new therapeutic opportunity to convert immune-suppressive macrophages to immuneenhancing macrophages. Jounce researchers were able to identify a specific "myeloid functional" epitope (the defined segment of the TIM-3 protein to which the antibody binds). In in vitro assays, only the antibodies directed to this epitope converted macrophages to a more immune active, anti-tumor type. While the "myeloid functional" anti-TIM-3 antibodies did not directly affect T cells, targeting TIM-3 on myeloid cells in this manner did have a secondary, stimulatory effect on the adaptive immune system.

"Our Beyond T Cell programs are based on the importance of targeting different immune cells types, outside of the T cell," said Deborah Law, D. Phil., chief scientific officer, Jounce. "It is our belief that this approach will allow us to pursue tumor types not currently served by therapies that target adaptive immune cells by potentially converting the tumor microenvironment from an immune-suppressive state to an immune activating, anti-tumor state. We are tremendously excited to present the first data from this program today as we work to develop myeloid-functional TIM-3 antibodies to expand the potential immunotherapeutic approaches beyond T cells. We think this approach has the potential to bring the benefits of immunotherapy to patients that are not responsive to current immunotherapies."
About the Jounce Translational Science Platform Jounce is working to develop therapies that enable the immune system to attack tumors, thereby bringing long-lasting benefits to patients. Jounce has developed its Translational Science Platform to use an unbiased bioinformatics-based approach to interrogate particular cell types within the human tumor microenvironment (the cellular environment that makes up a tumor). This platform is designed to prioritize targets and identify related biomarkers to match the right therapy to the right patients.

Seattle Genetics Highlights Novel Antibody-Drug Conjugate (ADC) Technology Advances at the American Association for Cancer Research (AACR) Annual Meeting

On April 17, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN) reported novel antibody-drug conjugate (ADC) technology advances presented at the 107th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held April 16 through 20, 2016 in New Orleans, LA (Press release, Seattle Genetics, APR 17, 2016, View Source;p=RssLanding&cat=news&id=2157672 [SID:1234510959]). Data in multiple presentations demonstrate the company’s leadership and innovation in the field of ADCs. Presentations will showcase a new auristatin-based drug-linker as well as several novel linkers that expand Seattle Genetics’ proprietary ADC technology platform and may enable application of previously inaccessible cytotoxic payloads.

"We have a comprehensive scientific understanding of the multiple components necessary to develop antibody-drug conjugates for the potential treatment of hematologic malignancies and solid tumors," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Our data presentations at the AACR (Free AACR Whitepaper) Annual Meeting illustrate novel linker systems and cell-killing payloads as well as continued progress in understanding the chemical and biological properties of ADCs to inform potential future development. We believe ADCs will continue to play an increasingly important role in cancer treatment."

ADCs are monoclonal antibodies designed to deliver cytotoxic agents selectively to tumor cells. Seattle Genetics has developed proprietary technology employing synthetic cytotoxic agents and stable linker systems that attach these cytotoxic agents to the antibody. Seattle Genetics’ linker systems are designed to be stable in the bloodstream and release the potent cell-killing agent once inside targeted cancer cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.

Multiple oral and poster presentations are being featured at AACR (Free AACR Whitepaper) that highlight Seattle Genetics’ ADC technology advances. Abstracts can be found at www.aacr.org and include the following:

Three poster presentations on Sunday and Monday, April 17 and 18, 2016 (Abstracts #0351, 1285, 2082) will highlight the role of the tumor microenvironment in ADC clearance, antitumor activity and uptake. Importantly, preclinical data demonstrate the potential for tumor associated macrophages to contribute to antitumor activity through release of MMAE.
The development of novel quaternary ammonium linkers for the stable conjugation and efficient release of tertiary amine-containing payloads will be presented in a poster presentation on Monday, April 18, 2016 (Abstract #2056). Preliminary data demonstrate that this technology enables the evaluation of drug classes previously inaccessible as ADCs, including auristatin E and tubulysin.

The development of a novel methylene-alkoxy-carbamate (MAC) linker that enables direct conjugation of drugs through alcohol functional groups will be presented in an oral presentation at 3:50 p.m. ET on Tuesday, April 19, 2016 (Abstract #4334). This linker has the potential to expand the types of payloads utilized in ADCs.
Data from a novel monomethyl auristatin E (MMAE) linker technology will be highlighted in a poster presentation on Tuesday, April 19, 2016 (Abstract #2956). By incorporating a short polyethylene glycol (PEG) unit, a self-hydrolysing maleimide and a glucuronidase release mechanism, the new MMAE drug-linker demonstrates pronounced activity with an increased therapeutic index in preclinical models.

Medivation Announces Presentation of Phase I Talazoparib Combination Data in Several Advanced Cancers

On April 17, 2016 Medivation, Inc. (NASDAQ: MDVN) reported that Phase I data from its investigational agent talazoparib, a highly-potent PARP inhibitor, was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans by the study’s lead investigator Zev A. Wainberg, M.D., Associate Professor of Medicine at the University of California Los Angeles (UCLA) and Co-Director of the UCLA GI Oncology Program, during a Clinical Trials Mini-Symposium (Press release, Medivation, APR 17, 2016, View Source [SID:1234510958]). The primary objective of the study was to determine the maximum tolerated dose (MTD) of talazoparib in combination with either low-dose temozolomide or low-dose irinotecan in heavily pretreated patients with advanced malignancies.

The data from the 40 patient trial demonstrated that combination treatment with talazoparib and low-dose chemotherapy resulted in stable disease or an objective response in 23 of 40 heavily pretreated patients with a variety of advanced cancers (clinical benefit rate of 58%). Most notably, objective responses were seen in four of seven (57%) heavily pre-treated non-BRCA-mutated ovarian cancer patients when talazoparib was used in combination with either low-dose temozolomide or low-dose irinotecan. Six of seven individuals (86%) with non-BRCA ovarian cancer had clinical benefit (four partial responses and two stable disease) and had a reduction in CA 125 levels by 50% or greater.

Importantly, the overall study demonstrated responses to combination talazoparib/low-dose chemotherapy in patients with multiple tumor types in which specific deleterious mutations in certain DNA repair genes extended beyond BRCA deficiency, including one patient who did not meet the criteria of having homologous recombination deficiency (HRD). These effects may be mediated through PARP inhibition, as well as enhanced PARP trapping, which interferes with the tumor cell’s ability to replicate DNA by locking PARP molecules onto the DNA strand.

"In non-clinical studies, talazoparib has been shown to have high potency specifically against PARP 1 and 2, and antitumor effects in various solid tumors. With these new results, we now have evidence in humans that suggests talazoparib in combination with low-dose chemotherapy is active in tumors with defects in DNA repair beyond BRCA deficiency, and possibly in patients without evidence of HRD. We feel these data are consistent with talazoparib’s potent PARP trapping ability, which we believe makes talazoparib a unique and exciting product candidate with the potential to be used in combination with DNA damaging therapies across a wide variety of tumor types," said David Hung M.D., Founder, President and Chief Executive Officer of Medivation. "With more than half of the ovarian cancer patients demonstrating an objective response, particularly in a heavily pre-treated patient population with advanced disease, these findings are encouraging and support further evaluation of the safety and efficacy of talazoparib."

Talazoparib currently is in Phase III development for patients with locally advanced and/or metastatic breast cancer who harbor a germline BRCA1/2 mutation. It is also being studied in several investigator-sponsored trials across multiple tumor types.

The Phase I investigator-sponsored study evaluated escalating doses of talazoparib ( ≥ 0.5 mg given orally once daily) with either temozolomide ( ≥ 25 mg/m2 given orally on days 1-5; Arm A) or irinotecan ( ≥ 25 mg/m2 given by intravenous infusion every two weeks; Arm B) every 28 days in patients with advanced malignancies. Study participants ranged in age from 21 to 77 years (median: 57 years) and had received one to 15 prior chemotherapy regimens (median: 6). The primary endpoint of the study was the determination of the MTD. Secondary endpoints included pharmacokinetics, tumor response and biomarkers.

A total of 40 patients received escalating doses of talazoparib (0.5-1.0 mg) and either temozolomide or irinotecan (18 patients in Arm A and 22 in Arm B). Results showed the MTD for talazoparib was 1.0 mg. and 37.5 mg/m2 for either temozolomide or irinotecan when combined with 1.0 mg talazoparib. Partial responses were seen in four of seven (57%) germline BRCA wild type ovarian cancer patients who were platinum-resistant. Additional responses were seen in one patient each with Ewing’s Sarcoma, cervical adenocarcinoma, small cell lung cancer, and triple negative breast cancer. An association was observed between response and the presence of deleterious somatic mutations in DNA repair genes (PALB2 and RAD51D) distinct from BRCA mutations.

The most common grade 3/4 adverse events ( ≥ 5%) observed in patients treated with talazoparib plus temozolomide were neutropenia (28%), anemia (33%), and thrombocytopenia (33%). Among those treated with talazoparib plus irinotecan, the most common adverse events were thrombocytopenia (13%), anemia (27%) and neutropenia (31%). No significant pharmacokinetic interactions were observed between talazoparib and either temozolomide or irinotecan.

About Talazoparib
Talazoparib is a potent and specific inhibitor of PARP 1 and 2(i) that is being developed by Medivation for the treatment of selected solid tumors. In pre-clinical studies, talazoparib has shown single-agent anti-tumor activity, as well as synergy in combination with lowered doses of DNA-damaging agents, due to its dual mechanisms of cytotoxicity, PARP trapping, and inhibition of PARP enzyme activity. Trapping of PARP on DNA impairs DNA replication resulting in tumor cell death. Talazoparib currently is in Phase III development for patients with locally advanced and/or metastatic breast cancer who harbor a germline BRCA1/2 mutation.

Loxo Oncology TRK Inhibitor LOXO-101 Shows Durable Anti-Tumor Activity Across TRK Fusion Cancers in AACR Phase 1 Update

On April 17, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported new results from its Phase 1 open-label, dose-escalation trial of LOXO-101, a selective inhibitor of tropomyosin receptor kinase (TRK) (Press release, Loxo Oncology, APR 17, 2016, View Source [SID:1234510957]). A presentation at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans on April 17, 2016 provided updated data from the Phase 1 trial, which was last reported at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in November 2015.

LOXO-101 Phase 1 study investigators reported that, as of the March 25, 2016 data cutoff date, 43 patients with solid tumors refractory to standard therapy had been enrolled and treated, including seven patients with cancers harboring TRK gene fusions. Data regarding the first three of these patients were initially reported at the AACR (Free AACR Whitepaper)-NCI-EORTC conference in November 2015.

Six patients with TRK fusion cancers had been on study sufficiently long for their first efficacy assessment, and all six exhibited significant tumor regressions. A seventh patient with a TRK fusion cancer was enrolled more recently and thus had not yet been evaluated for response as of the data cutoff date, though the patient remains on study. Five of the six efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. The sixth patient demonstrated clear radiographic tumor regressions, including in the central nervous system, but has not met the threshold required for a RECIST response. Tumor regressions have been observed in five different anatomically-defined cancers: sarcoma, gastrointestinal stromal tumor, mammary analogue secretory cancer of the salivary glands, thyroid cancer and non-small cell lung cancer. No TRK fusion patients have progressed, with one patient in cycle 14, two patients in cycle 10 and three patients in cycle 7, as of the data cutoff date. In addition, LOXO-101 has been highly active and well-tolerated at doses that include the recommended Phase 2 dose of 100 mg BID. The majority of adverse events reported by the investigators have been mild to moderate. A maximum tolerated dose (MTD) has not been defined.

"The responses, durability and safety data with LOXO-101 clearly suggest that this is an important drug candidate for patients with TRK fusion cancers," said David Hong, M.D., deputy chair and associate professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston and presenter of the LOXO-101 oral presentation. "We are excited to continue to follow these Phase 1 patients and treat additional TRK fusion patients in the LOXO-101 Phase 2 trial. I hope these data encourage my colleagues to test for TRK fusions and refer patients to a LOXO-101 study."

"The consistent efficacy of LOXO-101 in patients with TRK gene fusions, independent of tumor type, is very exciting," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "The data update also provides an encouraging snapshot of response durability, particularly at the recommended Phase 2 dose of 100mg twice-daily. These data suggest that LOXO-101 can deeply inhibit its target at a well-tolerated dose and generate durable disease control in a diverse group of patients with TRK gene fusions."

LOXO-101 Phase 1 Results
LOXO-101 is currently being evaluated in an ongoing dose-escalation Phase 1 trial in patients with solid tumors refractory to standard therapy. As of March 25, 2016, 43 patients with advanced cancer had been treated at five dose levels: 50 mg QD, 100 mg QD, 100 mg BID, 150 mg BID and 200 mg QD. The median age of these patients is 57 (ranging from 28-76) and the median number of prior treatments is three (ranging from 0-11).

Safety Analysis
LOXO-101 has been well tolerated in the 43 patients treated, including 24 patients at a dose of 100mg BID. Adverse events reported regardless of attribution to study drug are generally consistent with those previously presented. Grade 1 and 2 adverse events include fatigue (33 percent), constipation (23 percent) and dizziness (23 percent). Grade 3 adverse events included fatigue, constipation, anemia, increased liver enzymes, dyspnea, abdominal pain, hypertension, hyperkalemia, delirium, pleural effusion, and syncope. No Grade 4 adverse events have been reported. The frequency of toxicities did not correlate with dose level. The maximum tolerated dose (MTD) has not yet been defined.

Efficacy Analysis
As of March 25, 2016, seven patients with cancers harboring TRK fusions have been enrolled, representing a broad range of tumor types: mammary analogue secretory cancer of the salivary glands (MASC, n=3), soft tissue sarcoma, gastrointestinal stromal tumor, thyroid carcinoma and non-small cell lung cancer. As of the March 25, 2016 data cutoff date, six patients had been evaluated for response, and five had achieved a confirmed objective response. All six patients experienced significant tumor regression, with response status summarized below:

Soft tissue sarcoma, LMNA-NTRK1 fusion: Confirmed partial response, remains on study in cycle 14 at a dose of 100 mg BID
Gastrointestinal stromal tumor, ETV6-NTRK3 fusion: Confirmed partial response, remains on study in cycle 10 at a dose of 150 mg BID
MASC, ETV6-NTRK3 fusion: Confirmed partial response, remains on study in cycle 10 at 100 mg BID
MASC, ETV6-NTRK3 fusion: Confirmed partial response, remains on study in cycle 7 at 100 mg QD; this patient started therapy on 100 mg BID and dose-reduced early in cycle 1 to 100 mg QD due to transient dizziness possibly related to drug
Papillary thyroid cancer, ETV6-NTRK3 fusion: Confirmed partial response, remains on study in cycle 7 at 100 mg BID
Non-small cell lung cancer, TPR-NTRK1 fusion: 18% tumor regression of bone-only RECIST evaluable disease (stable disease), remains on study in cycle 7 at 100mg BID
All six patients remain on study as of March 25, 2016. The seventh patient was recently enrolled and not yet evaluable for efficacy as of the data cutoff date, but also remains on study.

On Monday, April 18, 2016, Loxo Oncology plans to file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the LOXO-101 materials presented at the AACR (Free AACR Whitepaper) meeting. These materials will also be posted to the Loxo Oncology website.

Upcoming Milestones for Loxo Oncology
Loxo Oncology continues to make significant progress across its pipeline. Upcoming milestones are expected to include:

Continued enrollment of the LOXO-101 Phase 2 global, multi-center, single-arm, open-label basket trial in adult patients with solid tumors that harbor a TRK fusion, with an enrollment update expected in the second half of 2016.
Initiation of a Phase 1 study of a selective RET inhibitor in late 2016 or early 2017.
Initiation of a Phase 1 study of next-generation TRK inhibitor LOXO-195, addressing previously-treated patients with acquired resistance, in 2017.
Conference Call and Webcast Information
Loxo Oncology will host a conference call, live webcast with slides and Q&A on Monday, April 18, 2016 at 8:00 a.m. ET to discuss the LOXO-101 data and program updates. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 77038770. A live webcast of the presentation will be available at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

About LOXO-101
LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions and a Phase 1 trial in pediatric patients. For additional information about the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.

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

On April 17, 2016 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported 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, ROS1 or ALK, were presented in an oral plenary session at the 2016 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in New Orleans, Louisiana (Press release, Ignyta, APR 17, 2016, View Source [SID:1234510954]).

"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 (Free AACR Whitepaper) 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 (Free AACR Whitepaper) 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 (Free AACR Whitepaper) 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 (Free AACR Whitepaper) 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 View Source, and will be archived and available at that site for 14 days.