On September 27, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported results from a Phase II trial demonstrating that its investigational therapy, ImmunoPulse IL-12, promotes tumor-specific, systemic anti-tumor immune responses in patients with Merkel cell carcinoma (MCC) (Press release, OncoSec Medical, SEP 27, 2015, View Source [SID:1234507581]). Shailender Bhatia, MD, Assistant Professor of Medicine, Division of Medical Oncology at the University of Washington School of Medicine and Principal Investigator of the trial, presented the findings today in an oral presentation at the 2015 European Cancer Congress in Vienna, Austria.

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"The successful completion of the first prospective trial of immunotherapy in MCC marks an important milestone," said Dr. Bhatia. "Importantly, our findings support the hypothesis that intratumoral IL-12 DNA with electroporation promotes tumor immunogenicity. The results confirm the potential of this approach to make a clinically meaningful impact on patient outcomes for this virus-associated cancer."

In this Phase II study, 79% of patients (11/14) showed an increase in IL-12 protein levels in tumor biopsy samples obtained approximately 22 days after treatment compared to baseline, indicating that ImmunoPulse IL-12 leads to successful DNA transfection and sustained protein expression within the tumor microenvironment. ImmunoPulse IL-12 was well-tolerated, with no treatment-related adverse events above Grade 2 and no treatment-related serious adverse events. The most common adverse event was Grade 1 transient pain associated with the treatment procedure.

Analysis of individual lesions found that 30% of patients (3/10) who were evaluable for systemic anti-tumor immunity had regression of at least one distant, non-injected/non-electroporated lesion. In patients considered evaluable for objective response by modified RECIST criteria (i.e., Cohort B, N=12), 25% of patients (3/12) had an objective partial response (PR) and one patient had stable disease (SD) for a disease control rate (PR + SD) of 33%. In Cohort A (N=3), one patient had a pathologic complete response and continues to be recurrence-free at six months. Another patient has been recurrence-free for over three years. Immune correlative data suggest that ImmunoPulse IL-12 can increase tumor-infiltrating lymphocytes and may promote a tumor-specific CD8+ T-cell response.

"We are very excited to observe that ImmunoPulse IL-12 continues to demonstrate that intratumoral treatment with IL-12 DNA and electroporation can induce anti-tumor immune effects both locally and systemically," said Mai H. Le, MD, Chief Medical Officer at OncoSec. "These results are consistent with what we have previously observed in metastatic melanoma and underscore the broad-reaching potential of ImmunoPulse IL-12 in driving immunogenicity."

About the Phase II Study Design
OMS-I110 was a Phase II open-label study that enrolled 15 patients with MCC. The primary endpoint of the trial was IL-12 protein expression following treatment with ImmunoPulse IL-12. Secondary endpoints included: safety and tolerability; overall response rate evaluated by RECIST-modified criteria for MCC; distant lesion regression; and biological markers of pro-inflammatory changes in the tumor microenvironment. Modifications to the standard RECIST criteria included permitting more than two measurable lesions per organ (e.g., skin) to be considered evaluable as "target lesions" and the use of a combination of clinical and radiographic measurements for lesion assessment.

Patients enrolled into this study were separated into two cohorts. Cohort A (N=3) was comprised of patients whose disease status was amenable to definitive surgery or radiation following a single cycle of ImmunoPulse IL-12 treatment (i.e., neo-adjuvant). Patients with more advanced disease were enrolled into Cohort B (N=12) and permitted to receive up to four cycles of ImmunoPulse IL-12.

About Merkel Cell Carcinoma (MCC)
MCC is a rare, aggressive cancer with a disease-associated mortality estimated to be three times that of malignant melanoma and affects approximately 1,600 people per year in the US.1-3 The reported incidence has more than tripled over the past 20 years and the health impact of MCC is growing rapidly with a proportional increase in the aging population.2-4 The reported five year relative survival for patients with local, nodal and metastatic disease is 64%, 39% and 18% respectively.1

Treatment options in the metastatic setting are limited for patients. Responses to chemotherapy regimens are usually short-lived and the impact on survival is unclear.5 Also, chemotherapy regimens are associated with toxicity and may not be suitable for MCC patients who tend to be older with multiple co-morbidities.5 Therefore, there is a strong unmet need for biology-driven therapies in MCC.

The recent discovery of the Merkel cell polyomavirus has provided the missing link between MCC and its association with immune suppression.5 MCC tumors are able to evade the immune system by establishing a local immunosuppressive microenvironment. Evidence shows the presence of intratumoral CD8+ T-cells are associated with better prognosis. As such, therapies aimed at promoting intratumoral inflammation may improve MCC patient outcomes.

On September 28, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported results from additional exploratory analyses of the Phase 3 SYNERGY trial demonstrating that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with metastatic castrate-resistant prostate cancer (mCRPC) (Press release, OncoGenex Pharmaceuticals, SEP 27, 2015, View Source [SID:1234507580]). In addition, these data presented at the 2015 European Cancer Congress (ECC 2015) in Vienna showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes.

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"These data support that custirsen is inhibiting the production of clusterin in men with metastatic CRPC and a correlation between treatment-induced reductions in sCLU and clinical benefit in those patients at risk for poor outcomes," said Scott Cormack, President and CEO of OncoGenex. "We look forward to top line results in metastatic CRPC patients at risk for poor outcomes later this year in our Phase 3 AFFINITY trial."

Production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Overproduction of clusterin, which occurs in response to a variety of cancer treatments, is associated with faster rates of cancer progression and shorter survival. Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer.

A previous retrospective analysis from the SYNERGY trial showed a benefit with custirsen therapy in men with metastatic CRPC who had at least two of five common risk factors for poor prognosis. For those men, a 27 percent lower risk of death occurred when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.

About the Study Results
(Abstract: 2560 – Baseline serum clusterin level in patients with poor prognostic features was associated with response to custirsen treatment: Results from the phase 3 SYNERGY trial of docetaxel +/- custirsen, Monday, September 28, 2015, 16:45 – 18:45 CEST, Hall C)

The analysis presented at ECC 2015 further demonstrates the impact of custirsen treatment on mCRPC patients at increased risk for poor outcomes, including a reduced risk of death among poor prognostic patients who achieved lower sCLU levels (Day 140 Area Under Curve (AUC)) during treatment. Patients in the poor prognostic subgroup who were treated with custirsen and had reduced Day 140 AUC sCLU levels showed a trend for higher two-year survival status. A landmark analysis also showed that overall survival benefit for the custirsen arm appeared greater in the poor prognostic patients who achieved lower Day 140 AUC sCLU levels.

In patients with lower sCLU at baseline, a trend for greater effect of custirsen treatment on survival was also observed, especially in patients at increased risk for poor outcomes. Patients at risk for poor outcomes with low baseline sCLU treated with custirsen (n=176) experienced a median survival of 18.4 months, compared to 14.4 months for patients on the control arm (n=170) [HR=0.689 (95% CI: 0.483-0.983); the median baseline sCLU was 55.30 ug/mL for patients at risk for poor outcomes. In the subpopulation of patients with a good prognosis, patients with low baseline sCLU treated with custirsen (n=171) experienced a median survival of 31.2 months in comparison to 27.2 months for patients on the control arm (n=186) [HR = 0.823 (95% CI: 0.505-1.34); the median baseline sCLU was 53.2 ug/mL for patients with a good prognosis.

Apatorsen Update
(Abstract: 2637 – Baseline circulating tumor cells (CTC) and serum heat shock protein 27 (Hsp27) levels are increased in advanced bladder cancer (BC) patients with poor prognostic factors: Results from the randomized phase 2 Borealis-1TM trial of first-line gemcitabine/cisplatin plus apatorsen or placebo, Monday, September 28, 2015, 16:45 – 18:45 CEST, Hall C)

Results from the company’s other lead product candidate, apatorsen, presented at ECC 2015 confirmed that patients with advanced bladder cancer at increased risk for poor outcomes had increased baseline levels of circulating tumor cells (CTC) and of serum heat shock protein 27 (Hsp27). The study showed that baseline Hsp27 and CTC levels were independent risk factors for survival outcomes.

"Apatorsen is designed to inhibit the production of Hsp27 and thereby to disable cancer cells’ defenses and overcome treatment resistance that is common in this disease," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "Patients in the Borealis-1TM trial with advanced disease who had specific poor prognostic risk factors experienced a clinical benefit with apatorsen. We are continuing to work closely with investigators and regulatory agencies to determine next steps as we collect more evidence regarding apatorsen’s activity in this disease."

Data from the Borealis-1 trial previously reported at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting earlier this year showed that metastatic bladder cancer patients with poor prognostic features (low performance status, liver involvement, low hemoglobin and high alkaline phosphatase) showed a potential survival benefit with apatorsen 600mg added to first-line chemotherapy (HR = 0.72) compared to chemotherapy alone. Patients in the trial with a Karnofsky Performance Status of 80 percent or less, a common indicator of poor prognosis, experienced a 50 percent reduction in risk of death with the addition of apatorsen therapy (HR = 0.50).

Completion of enrollment in the Phase 2 Borealis-2 bladder cancer trial is expected to occur by the end of 2015 and will evaluate apatorsen in combination with docetaxel in patients with advanced or metastatic bladder cancer who have disease progression following first-line platinum-based chemotherapy.

About Clusterin

A major barrier to extending survival in patients with advanced cancer is treatment failure due to the ability of tumor cells to exploit fundamental cellular mechanisms that allow them to evade destruction by anti-cancer therapies. The production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients.

About Custirsen

Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells. Custirsen binds to clusterin mRNA to block the production of clusterin protein and has enhanced the tumor cell destructive effects of multiple anti-cancer therapies across a variety of tumor models. By inhibiting clusterin, custirsen is designed to alter tumor dynamics by slowing tumor growth and inhibiting tumor resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

Custirsen has Fast Track designation by the U.S. Food and Drug Administration for metastatic CRPC and non-small cell lung cancer.

About Apatorsen and ORCA
Apatorsen (OGX-427) is designed to inhibit production of heat shock protein 27 (Hsp27), disable cancer cells’ defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival.

The ORCA (Ongoing Studies Evaluating Treatment Resistance in CAncer) program encompasses clinical trials of apatorsen. Phase 2 clinical trials are underway in bladder, lung, pancreatic and prostate cancers. For more information on apatorsen and ORCA, please visit www.OncoGenex.com or www.orcatrials.com.

On September 28, 2015 Novartis treported updated data from the Phase III COMBI-v study showing a significant overall survival benefit for patients with BRAF V600E/K mutation-positive metastatic melanoma when treated with the combination of Tafinlar (dabrafenib) + Mekinist (trametinib) compared to vemurafenib monotherapy (Press release, Novartis, SEP 27, 2015, View Source;year=2015 [SID:1234507578]). The combination also demonstrated significant health-related quality of life improvements in the trial, including overall health, physical and social functioning. Results are being presented at the European Cancer Congress 2015 in Vienna.

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"It is remarkable to see so many patients with BRAF V600E/K mutation-positive metastatic melanoma having long term responses and obtaining a significant decrease of the risk of death as compared with vemurafenib monotherapy," said Caroline Robert, MD, PhD, Head of Dermatology, Institute Gustave-Roussy. "This is the second Phase III trial of Tafinlar + Mekinist combination therapy to demonstrate a significant overall survival benefit over BRAF inhibitor monotherapy, further establishing Tafinlar + Mekinist as a standard of care for patients fighting BRAF V600 mutation-positive metastatic melanoma."

The significant overall survival benefit of Tafinlar + Mekinist from COMBI-v is consistent with the results demonstrated by the combination in COMBI-d, another Phase III trial previously reported at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting earlier this year.

In the COMBI-v study, the combination of Tafinlar + Mekinist achieved a statistically significant overall survival (OS) benefit compared to vemurafenib monotherapy (median for the combination 25.6 months vs 18.0 months; HR 0.66 [95% CI, 0.53-0.81], p<0.001). The rate of OS at two years was 51% for those receiving the Tafinlar + Mekinist combination and 38% for those receiving vemurafenib monotherapy[3]. In addition, the median overall response rate (ORR) was 65.6% in patients receiving the Tafinlar + Mekinist combination compared to 52.8% for those receiving vemurafenib monotherapy. The safety results from this study were consistent with the profile observed to date for the combination; no new safety concerns were observed[3].

"Helping patients live longer with our targeted combination therapy, Tafinlar and Mekinist, is very gratifying," said Bruno Strigini, President, Novartis Oncology. "This exemplifies our mission to transform cancer care with the ultimate goal of identifying the right treatment for the right patient at the right time."

Metastatic melanoma is the most serious and life-threatening type of skin cancer[1] and only about one in five patients survives for five years following diagnosis with late-stage disease[2]. There are about 200,000 new cases of melanoma diagnosed worldwide each year[4], approximately half of which have BRAF mutations[2]. Gene tests can determine whether a tumor has a BRAF mutation, and results can play a key role in prognosis and determining appropriate treatment[2].

In August 2015, the European Commission approved the combination of Tafinlar + Mekinist for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. The European Commission approval applies to all 28 EU member states, plus Iceland, Norway and Liechtenstein. In July 2015, the US Food and Drug Administration (FDA) granted priority review for an application to obtain regular approval of the Tafinlar + Mekinist combination in BRAF V600E/K mutation-positive metastatic melanoma. Since January 2014, the combination of Tafinlar + Mekinist has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The combination was approved through the FDA’s Accelerated Approval program and reviewed under a priority review designation. The approval was contingent on the results of the COMBI-d study, which was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation.

About the COMBI-v Study
COMBI-v was a two-arm, open-label, Phase III study comparing the combination of Tafinlar + Mekinist with vemurafenib monotherapy in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. The primary endpoint of this study was OS[3].

Results from the COMBI-v study showed that the combination of Tafinlar + Mekinist achieved a statistically significant OS benefit compared to vemurafenib monotherapy (median for the combination 25.6 months vs 18.0 months; HR 0.66 [95% CI, 0.53-0.81], p<0.001). A statistically significant reduction of 34% in the risk of death among patients receiving combination therapy was observed in the study. The analysis reported median progression free survival (PFS) of 12.6 months, ORR of 65.6%, and median duration of response (DoR) of 13.8 months for the Tafinlar + Mekinist combination arm compared to PFS of 7.3 months, ORR of 52.8%, and median DoR of 8.5 months for the vemurafenib monotherapy arm. The most frequent adverse events in the Tafinlar + Mekinist combination arm (>=30%) were pyrexia, nausea, diarrhea, and chills. More patients had AEs leading to dose modifications in the combination arm compared to the vemurafenib monotherapy arm. For the combination group compared to the vemurafenib group, there was a lower incidence of rash, 22% (n=76) vs 43% (n=149); photosensitivity reaction, 4% (n=13) vs 22% (n=78); hand-foot syndrome, 4% (n=14) vs 25% (n=87); skin papillomas, 2% (n=6) vs 23% (n=80); squamous-cell carcinomas and keratoacanthomas, 1% (n=5) vs 18% (n=63); and hyperkeratosis, 4% (n=15) vs 25% (n=86). Adverse events occurring more frequently in the combination arm compared with the vemurafenib monotherapy arm included pyrexia, 53% (n=184) vs 21% (n=73), respectively, and bleeding events, 18% (n=62) vs 7% (n=25), respectively. Discontinuation of treatment due to adverse events was similar between the treatment groups: 13% (n=44) for the combination group compared to 12% (n=41) for the monotherapy group[3].

Results from an analysis of the COMBI-v study of the patients’ health-related quality of life showed statistically significant and clinically meaningful improvements among those receiving the combination of Tafinlar + Mekinist, compared to those receiving vemurafenib monotherapy. Overall health, physical and social functioning, and specific symptoms such as pain, insomnia, and loss of appetite were all improved in the group receiving combination therapy[5].

About Tafinlar + Mekinist Combination
Combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the US, EU, Australia, Canada and additional countries.

Tafinlar and Mekinist target different kinases within the serine/threonine kinase family – BRAF and MEK1/2, respectively – in the RAS/RAF/MEK/ERK pathway, which is implicated in NSCLC and melanoma, among other cancers. When Tafinlar is used with Mekinist, the combination has been shown to slow tumor growth more than either drug alone. The combination of Tafinlar + Mekinist is currently being investigated in an ongoing clinical trial program across a range of tumor types conducted in study centers worldwide.

In 2015, as part of its purchase of oncology products from GlaxoSmithKline, Novartis obtained the worldwide exclusive rights granted by Japan Tobacco Inc. (JT) to develop, manufacture, and commercialize trametinib. JT retains co-promotion rights in Japan.

The safety and efficacy profile of the Tafinlar + Mekinist combination has not yet been established outside of the approved indication.

Tafinlar and Mekinist are also indicated in more than 35 countries worldwide, including the US and EU, as single agents to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Tafinlar + Mekinist Combination Important Safety Information for Metastatic Melanoma
Tafinlar + Mekinist combination may cause serious side effects, such as:

When Tafinlar is used in combination with Mekinist, or when Tafinlar is administered as monotherapy, it can cause new cancers (both skin cancer and non-skin cancer). Patients should be advised to contact their doctor immediately for any new lesions, changes to existing lesions on their skin, or signs and symptoms of other malignancies.

Before taking Tafinlar in combination with Mekinist, doctors should test their patients for BRAF wild-type melanoma, as patients without BRAF mutation and with RAS mutation can be at risk of increased cell proliferation in the presence of a BRAF inhibitor.

When Tafinlar is used in combination with Mekinist, it can increase the incidence and severity of bleeding, and in some cases can lead to death. Patients should be advised to call their healthcare provider and get medical help right away if they have headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," have red or black stools that look like tar, or any unusual signs of bleeding.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

Tafinlar in combination with Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their healthcare provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar alone, or in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their healthcare provider right away if they get these symptoms of eye problems: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Patients should notify their doctor if they experience any new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Tafinlar alone or in combination with Mekinist can cause fever, which may be serious. When taking Tafinlar in combination with Mekinist, fever may happen more often or may be more severe. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their healthcare provider right away if they get a fever above 38.5oC (101.3oF) while taking Tafinlar.

Rash is a common side effect of Tafinlar alone, or when used in combination with Mekinist. Tafinlar alone, or in combination with Mekinist, can also cause other skin reactions. In some cases these rashes and other skin reactions can be severe, and may need to be treated in a hospital. Patients should be advised to call their healthcare provider if they get any of the following symptoms: skin rash that bothers them or does not go away, acne, redness, swelling, peeling, or tenderness of hands or feet, skin redness.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar, alone or in combination with Mekinist. For patients who are diabetic, their healthcare provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their healthcare provider if they have any of the following symptoms of severe high blood sugar: increased thirst or urinating more often than normal, or urinating an increased amount of urine.

Tafinlar may cause healthy red blood cells to break down too early in people with G6PD deficiency. This may lead to a type of anemia called hemolytic anemia where the body does not have enough healthy red blood cells. Patients should be advised to tell their healthcare provider if they have any of the following signs or symptoms of anemia or breakdown of red blood cells: yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar and Mekinist both can cause harm to an unborn baby when taken by a pregnant woman. Tafinlar can also render hormonal contraceptives ineffective.

The most common side effects of Tafinlar + Mekinist combination include fever, nausea, tiredness, rash, chills, diarrhea, headache, vomiting, hypertension, joint pain, peripheral edema and cough. The incidence and severity of fever is increased when Mekinist is used in combination with Tafinlar.

Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Tafinlar + Mekinist combination. For more information, patients should ask their doctor or pharmacist.

Patients should take Tafinlar + Mekinist combination exactly as their health care provider tells them. Patients should not change their dose or stop taking Tafinlar + Mekinist combination unless their health care provider advises them to. Mekinist should be taken only once daily (either in the morning or evening, at the same time as Tafinlar). The first and second dose of Tafinlar should be taken approximately 12 hours apart. Patients should take Tafinlar + Mekinist at least 1 hour before or 2 hours after a meal. Do not take a missed dose of Tafinlar within 6 hours of the next dose of Tafinlar. Do not open, crush, or break Tafinlar capsules. Do not take a missed dose of Mekinist within 12 hours of the next dose of Mekinist.

Please see full Prescribing Information for Tafinlar and Mekinist.

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.