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NewLink Genetics Corporation Announces Promising Clinical Data at European Cancer Congress 2015 (ECC)

On September 27, 2015 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates to improve the lives of patients with cancer, reported promising early-stage clinical data from a phase 1a study of GDC-0919, an IDO checkpoint inhibitor being developed in collaboration with Genentech, a member of the Roche Group, was presented today at the European Cancer Congress 2015 (ECC) in Vienna, Austria (Press release, NewLink Genetics, SEP 27, 2015, View Source [SID:1234507576]).

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The data reported today are from a Phase 1a study of the safety, pharmacokinetics and pharmacodynamics of GDC-0919 in 19 patients with recurrent or advanced solid tumors. The primary objectives of this study are to evaluate the safety and tolerability of GDC-0919 in patients with advanced solid tumors as well as to define the maximum tolerated dose (MTD) or maximum biologically effective dose and recommended Phase 2 dose. GDC-0919, a small molecule investigational immunotherapy designed to inhibit IDO1 for the treatment of immune tolerance associated with cancer, is intended as a combination therapy with other immunotherapies and oncology therapeutics.

The data showed an acceptable safety profile, disease stabilization and preliminary evidence of peripheral pharmacodynamic modulation.

GDC-0919 was well tolerated up to 800 mg BID (twice daily) on a 21/28 day cycle. Thirty seven percent of patients available for tumor assessments (7/17) achieved stable disease. The MTD was not reached.

Single and multiple dose exposure from 50 to 800 mg of GDC-0919 increased in approximately dose-proportional manner, and higher doses of GDC-0919 modulated plasma Kynurenine in a manner consistent with the half-life of GDC-0919.

The most common adverse events related to GDC-0919 were lower grade and included pruritus or itching (37%), fatigue, (26%) and decreased appetite (21%).

The study continues to evaluate safety, PK, activity and pharmacodynamics of GDC-0919 at a continuous dosing schedule (BID 28/28) to enable greater flexibility in future dosing regimens. GDC-0919 also is being evaluated in a Phase 1b study in combination with atezolizumab (PD-L1 inhibitor) in patients with recurrent or advanced solid tumors.

About NewLink Genetics’ IDO Collaboration with Genentech

NewLink Genetics entered into an exclusive worldwide license agreement with Genentech in October 2014 for the development of GDC-0919, NewLink Genetics’ IDO checkpoint inhibitor, previously known as NLG919. The parties also entered into a research collaboration for the discovery of next generation IDO/TDO compounds.

Under the terms of the agreement, NewLink Genetics received an upfront payment of $150 million and will be eligible to receive in excess of $1 billion in milestone payments based on achievement of certain predetermined milestones as well as escalating double-digit royalties on potential commercial sales of multiple products by Genentech.

Genentech continues to fund future research, development, manufacturing and commercialization costs and also provides research funding to NewLink Genetics for support of the research collaboration. NewLink Genetics retains the option for co-promotion rights for GDC-0919 and potential next generation IDO/TDO compounds in the U.S.

New Data from KEYNOTE-028, Merck’s Trial Evaluating KEYTRUDA® (pembrolizumab) Across a Range of Cancer Types, Presented at 2015 European Cancer Congress

On September 27, 2015 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported new findings from the KEYNOTE-028 Phase 1b study, the clinical trial investigating the use of the company’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in multiple, difficult-to-treat cancers (Press release, Merck & Co, SEP 27, 2015, View Source [SID:1234507574]). Data from this trial, to be presented at the European Cancer Congress (ECC) in Vienna, Austria, Sept. 25-29, include the first-time findings for KEYTRUDA in two gastrointestinal cancers, advanced anal cancer and advanced biliary tract cancer, and add to Merck’s growing body of clinical data for KEYTRUDA.

KEYNOTE-028 is an ongoing multi-cohort, non-randomized Phase 1b basket trial – a trial design that allows for the study of multiple sub-populations of different tumor or histological types within one study. The study is evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA monotherapy (10 mg/kg dosed every two weeks) in more than 450 patients across 20 different types of cancer. The study was designed to evaluate patients with advanced solid tumors that express PD-L1 and which have not responded to current therapy or for which current therapy is not appropriate.

"Through innovative trials like KEYNOTE-028, we are advancing our understanding of the potential benefit of KEYTRUDA in a wide range of difficult-to-treat cancers," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "Merck is committed to evaluating KEYTRUDA across as many tumor types as possible and the expansion of our clinical development program over the years reflects this. We are encouraged by these early stage data, and will continue to advance KEYTRUDA in order to deliver on our goal of helping as many people with cancer as possible."

The KEYTRUDA clinical development program has rapidly expanded to encompass more than 30 tumor types in more than 130 clinical trials, of which more than 70 trials combine KEYTRUDA with other cancer treatments. Registration-enabling trials of KEYTRUDA monotherapy are currently enrolling patients in melanoma, non-small cell lung cancer (NSCLC), head and neck cancer, bladder cancer, gastric cancer, colorectal cancer, and Hodgkin Lymphoma, with further trials in planning for other cancers.

Early Findings from Advanced Squamous Cell Carcinoma (SCC) of the Anal Canal (Abstract #500)

Early findings from 25 heavily pre-treated patients with advanced anal cancer – to be presented in an oral session on Sunday, Sept. 27 by Dr. Patrick Ott, Dana-Farber Cancer Institute – demonstrated an overall response rate (ORR) of 20 percent (confirmed and unconfirmed) (95% CI, 6.8-40.7) and a disease control rate (DCR) of 64 percent (95% CI, 42.5-82.0). Five partial responses (95% CI, 6.8-40.7) were observed, and 44 percent of patients (n=11/25) had stable disease (95% CI, 24.4-65.1). Additionally, the 6-month progression-free survival (PFS) rate was 31.6 percent and the 12-month PFS rate was 19.7 percent. At the time of the analysis, response duration ranged from 0.1+ to 9.2+ months, with the median not yet reached. The median stable disease duration was 3.6 months (range, 1.8+ to 11.0+).

Adverse events were generally consistent with previously reported safety data for KEYTRUDA. Grade 3-4 investigator-assessed, treatment-related adverse events were thyroid-stimulating hormone increased (n=1), colitis (n=1), diarrhea (n=1), and general physical health deterioration (n=1). Immune-mediated adverse events were hypothyroidism (n=3) and colitis (n=1). There were no treatment-related deaths.

Early Findings from Advanced Biliary Tract Cancer (Abstract #525)

Early findings from 24 heavily pre-treated patients with advanced biliary tract cancer – presented in a poster session on Saturday, Sept. 26 by Dr. Yung-Jue Bang, Seoul National University Hospital, Seoul, Korea – demonstrated an ORR of 17.4 percent (confirmed and unconfirmed) (95% CI, 5.0-38.8) (n=4/23); 17.4 percent of patients had stable disease (95% CI, 5.0-38.8) (n=4/23). As the time of the analysis, three of four responses were ongoing, and the median response duration had not yet been reached (range, 5.4+ to 9.3+ weeks).

Adverse events were generally consistent with previously reported safety data for KEYTRUDA. Grade 3-4 investigator-assessed, treatment-related adverse events were anemia (n=1), autoimmune hemolytic anemia (n=1), colitis (n=1) and dermatitis (n=1). Immune-mediated adverse events were autoimmune hemolytic anemia (n=1), colitis (n=1), hypothyroidism (n=1), and hypothyroidism (n=1). There were no treatment-related deaths.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until metabolic control is achieved.

Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. The following clinically significant immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis.

For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients. Adverse reactions, reported in at least two patients, that led to discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients. The most frequent serious adverse reactions, reported in 2% or more of patients, were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

Ignyta Announces Updated Interim Data from Entrectinib Phase 1 Clinical Trials at the 2015 European Cancer Congress

On September 27, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported that updated interim results of its Phase 1 clinical trials of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors that harbor activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK, were presented in an oral presentation session at the 2015 European Cancer Congress (ECC 2015) in Vienna, Austria (Press release, Ignyta, SEP 27, 2015, View Source [SID:1234507570]).

"We continue to be excited by the data from our two Phase 1 clinical trials of entrectinib, particularly in patients who would meet the anticipated eligibility criteria for our planned Phase 2 clinical trials," said Pratik Multani, M.D., Chief Medical Officer of Ignyta. "Out of the 18 patients in the two studies who met these criteria, we observed 13 responses, for an overall response rate of 72% across multiple tumor histologies. In addition, based upon an increased dataset of 92 patients, we have been able to confirm entrectinib’s acceptable safety profile for further development at the recommended phase 2 dose (RP2D). We intend to use this clinical experience as the basis for STARTRK-2, our planned, potentially registration-enabling Phase 2 clinical trial of entrectinib."

The 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, as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant molecular alterations: NTRK1 (encoding TrkA), ROS1 or ALK for ALKA-372-001 and NTRK1/2/3 (encoding TrkA/TrkB/TrkC), ROS1 or ALK for STARTRK-1.

As of the August 15, 2015, data cut-off for the presentation, the findings showed:

A total of 92 patients with a range of solid tumors had been dosed across both clinical trials, with nine patients treated at or above the RP2D beyond six months and one patient beyond one year.

Entrectinib was well tolerated to date:
Across both studies, the most frequent (>10% incidence) treatment-related adverse events were fatigue, dysgeusia, paresthesia, nausea, and myalgia. Seven of these were Grade 3 in severity, consisting of fatigue (4 patients), cognitive impairment (2 patients), and diarrhea (1 patient). No Grade 4 treatment-related adverse events were observed;

Across both studies, there were only three treatment-related serious adverse events: Grade 3 cognitive impairment and Grade 3 myocarditis, both of which occurred above the RP2D, and Grade 2 fatigue. All events were reversible and resolved upon dose modification;

The fixed daily dose RP2D was determined to be 600 mg, taken orally once per day (QD);
18 patients across both clinical trials met the company’s expected Phase 2 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;

The response rate in the 18 patients who met these criteria across both studies was 72% (13 responses out of 18 treated patients, as assessed by the clinical sites). Nine of these responders remain on study treatment with durable responses of up to 21 treatment cycles. An additional 3 patients remain on study with stable disease. The responses included:

3 responses out of 4 patients with NTRK1/2/3 gene rearrangements, including patients with non-small cell lung cancer (NSCLC), colorectal cancer and salivary gland cancer, with one of the responding patients remaining on treatment at 6 months; a fourth patient with an astrocytoma remains on treatment after two months with stable disease;

6 responses, including one complete response, out of 8 patients with ROS1 gene rearrangements, all of which were in NSCLC. All of the patients who responded remain on treatment, the longest at 21 months; and

4 responses out of 6 patients with ALK gene rearrangements, including two NSCLC patients and two patients with other solid tumors; two of the 4 responders subsequently progressed.

Entrectinib has demonstrated objective tumor response in the central nervous system (CNS), a frequent site of metastases and progression of advanced solid tumors.

On Wednesday, September 30, 2015, Ignyta will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the materials presented at the ECC 2015. 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.

Hospira Japan Receives Approval of Additional Dosage/Administration for "Paclitaxel I.V. infusion [Hospira]"

On September 27, 2015 Hospira Japan Co., Ltd. reported that the company has received an approval for the additional dosage/administration of gastric cancer for "Paclitaxel I.V. infusion [Hospira]" by a new drug application (NDA) based on evidence in the public domain with the Ministry of Health, Labour and Welfare (MHLW) in Japan (Press release, Hospira, SEP 27, 2015, View Source;p=RssLanding&cat=news&id=2090640 [SID:1234507569]).

[Product name]
1. Paclitaxel I.V. lnfusion 30mg/5mL [Hospira]
2. Paclitaxel I.V. lnfusion 100mg/16.7mL [Hospira]

[Therapeutic Category]
Anticancer drug

[Dosage /administration for gastric cancer]
The underlined text represents the additional dosage/administration.

Method A or E are used for gastric cancer.
Method A: Normally for adults 210 mg/m2 (body surface area) in terms of Paclitaxel is administered over 3 hours in a single infusion, with intervals of at least three weeks between doses. This forms one course, which is repeated.
Method E: Normally for adults 80 mg/m2 (body surface area) in terms of paclitaxel is administered over 1 hour in a single infusion, once per week for three successive weeks, followed by an interval of at least two weeks. This forms one course, which is repeated.
Doses may be suitably reduced having regard to the condition of the patient.

On the basis of the requirement of the additional dosage/administration for gastric cancer for originator, which includes Paclitaxel, the report was prepared by the "Review Committee on Unapproved Drugs and Indications with High Medical Needs." The decision was made based on the report at the meeting of the Second Committee on New Drugs, Pharmaceutical Affairs and Food Sedation Council, held on March 5, 2015, which confirmed that filing through the "NDA based on evidence in the public domain" was reasonable for this additional dosage/administration.

The MHLW notification related to "NDA based on evidence in the public domain" for generics recommends pharmaceutical companies work on filing for additional dosage/administration for generic at the same time as originators. Hospira Japan filed this additional dosage/administration for "Paclitaxel I.V. infusion 30mg/5mL [Hospira] " and "Paclitaxel I.V. infusion 100mg/16.7mL [Hospira] " by "NDA based on evidence in the public domain."

Hospira Japan is committed to contributing to healthcare in Japan by providing value-added products with its broad portfolio and meeting the expectations of patients and healthcare professionals.

Roche presents positive results from pivotal study of investigational immunotherapy atezolizumab in specific type of advanced bladder cancer at 2015 European Cancer Congress

On September 27, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) treported early results from a pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC) (Press release, Hoffmann-La Roche , SEP 27, 2015, View Source [SID:1234507567]). The study showed that atezolizumab shrank tumours (objective response rate, ORR) in 27 percent of people with mUC whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Ninety-two percent of people who responded to atezolizumab continued to respond when the results were assessed. Median duration of response was not yet reached. Adverse events were consistent with those observed in previous studies.

"These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed."

Roche is planning to submit these data to global health authorities and to the FDA under a Breakthrough Therapy Designation for the treatment of people whose metastatic bladder cancer expresses PD-L1. This designation is designed to expedite the development and review of medicines intended to treat serious diseases that may demonstrate substantial improvement over existing therapies.

About the IMvigor 210 study
These final results from cohort 2 of this study (minimum of 24 weeks’ follow-up) will be presented in an oral session presentation by Jonathan E. Rosenberg, MD, Memorial Sloan Kettering Cancer Center, USA (Abstract #21LBA) on Sunday, 27 September, 10:40 Central European Time (CET).

Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210).

IMvigor 210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or mUC, but who were ineligible for first-line cisplatin-based therapy; results for this cohort are not yet mature. Cohort 2, for which results were announced today, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. People received a 1200-mg intravenous dose of atezolizumab on day one of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2).

The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety. People were selected by histology, prior lines of therapy and PD-L1 expression on tumour-infiltrating immune cells (IC), using an investigational immunohistochemistry (IHC) test that is being developed by Roche Diagnostics.