On September 27, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported longer term (18 month) survival data from CheckMate -057, an open-label, randomized Phase 3 study evaluating Opdivo (n=292) versus docetaxel (n=290) in previously treated patients with advanced, non-squamous (NSQ) non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, SEP 27, 2015, View Source [SID:1234507560]). Opdivo continued to demonstrate superior overall survival (OS) – the study’s primary endpoint – with an estimated 39% of patients alive at 18 months (95% CI, 34-45) versus 23% for docetaxel, based on a minimum follow-up of 17.1 months. Opdivo also continued to demonstrate a reduction in the risk of death by 28% (a hazard ratio of 0.72; 95% CI, 0.60 – 0.88). In the study, Grade 3-4 treatment-related adverse events were reported in 10% of patients treated with Opdivo versus 54% in the docetaxel arm. These data will be presented on Monday, September 28 during the 2015 European Cancer Congress (ECC 2015) (Abstract # 3010) and published in the New England Journal of Medicine.

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"These longer term survival results for nivolumab in advanced, non-squamous non-small cell lung cancer support the potential for this Immuno-Oncology agent in treating lung cancer patients," said Leora Horn, M.D., Vanderbilt-Ingram Cancer Center. "CheckMate -057 builds upon its critical findings and now, data show a sustained survival benefit for nivolumab in this hard-to-treat disease that is incredibly encouraging for oncologists, and most importantly, for our patients."

CheckMate -057 clinical results were first reported at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), marking the first time a PD-1 inhibitor demonstrated superior OS versus docetaxel in previously treated patients with NSQ NSCLC. Data from this trial have been accepted for regulatory review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency to expand the respective Opdivo indications to include previously treated patients with NSQ NSCLC. This application has also been granted Priority Review in the U.S., and Opdivo has received Breakthrough Therapy Designation for this indication.

"At the core of our Immuno-Oncology approach is an unrelenting focus to fundamentally change survival expectations for all cancer patients. Today, we are driving insights into how advanced lung cancer may be treated – from defining the role of PD-L1 expression to showing clinical efficacy resulting in deep and durable responses for these patients," said Michael Giordano, senior vice president, head of Development, Oncology. "The 18-month data from CheckMate -057 reinforce the potential for Opdivo, across PD-L1 expression levels, to offer patients durable overall survival benefit with lower incidence of serious adverse events versus chemotherapy."

About CheckMate -057

CheckMate -057 is a Phase 3, open-label, randomized clinical trial that evaluated patients with advanced NSQ NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The trial included patients regardless of their PD-L1 status. Secondary endpoints included objective response rate (ORR) and progression-free survival (PFS). Patients enrolled in the trial received Opdivo 3 mg/kg every two weeks versus standard of care, docetaxel, at 75 mg/m2 every three weeks. In the trial, Opdivo demonstrated continued superior OS benefit, with an estimated 51% of patients alive at one year versus 39% for docetaxel, and an estimated 39% of patients alive at 18 months (95% CI, 34-45) versus 23% for docetaxel, based on a minimum follow-up of 17.1 months.

CheckMate -057 also evaluated the efficacy of Opdivo by tumor PD-L1 expression. Of randomized patients, 78% (455/582) had tumor samples evaluable for PD-L1 expression. Rates of PD-L1 expressing tumors were balanced between groups. PD-L1 status was predictive for benefit from Opdivo, across pre-specified 1%, 5%, and 10% expression levels. In PD-L1 non-expressors, OS was similar between Opdivo and docetaxel, with improved durability of responses seen in patients treated with Opdivo versus docetaxel.

In addition, clinical results showed confirmed ORR was significantly higher for Opdivo (19%) than docetaxel (12%). For patients administered Opdivo, median duration of response was 17.2 months and 5.6 months for docetaxel. One-year PFS was 19% for Opdivo (95% CI, 14-23) and 8% for docetaxel (95% CI, 5-12). Median PFS was 2.3 months for Opdivo (95% CI, 2.2-3.3) and 4.2 months for docetaxel (95% CI, 3.5-4.9).

The safety profile of Opdivo in CheckMate -057 was consistent with prior studies and similar across expressors and non-expressors. Treatment-related adverse events were low in severity with Opdivo and occurred less frequently (any grade: 69%; grade 3-4: 10%) than docetaxel (any grade: 88%; grade 3-4: 54%), including both hematologic and non-hematologic toxicities. Treatment-related serious adverse events were reported less frequently with Opdivo (any grade: 7%; grade 3-4: 5%) than docetaxel (any grade: 20%; grade 3-4: 18%). Discontinuation due to treatment–related adverse events was less frequent with Opdivo (5%) than docetaxel (15%).

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization. Lung cancer results in more deaths worldwide than colorectal, breast and prostate cancers combined. Non-small cell lung cancer is one of the most common types of the disease and accounts for approximately 85% of cases.

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 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 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 27, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from two phase II studies that evaluated the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with advanced non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche , SEP 27, 2015, View Source [SID:1234507566]). In the randomised phase II study, POPLAR, atezolizumab met its primary endpoint and showed a statistically significant survival benefit compared to chemotherapy (HR=0.54; p=0.014) in people with recurrent NSCLC whose tumours expressed medium and high levels of PD-L1, which corresponded with people living 7.7 months longer than people who received docetaxel chemotherapy. A separate, single-arm phase II study, BIRCH, met its primary endpoint and showed that atezolizumab shrank tumours (objective response rate, ORR) in up to 27 percent (p=0.0001) of people whose disease had progressed on prior medicines and also expressed the highest levels of PD-L1. Median survival had not yet been reached. In both studies of atezolizumab, adverse events (AEs) were consistent with those observed in previous studies.

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"Results from both of our studies in non-small cell lung cancer showed that measuring PD-L1 may help identify people most likely to respond to atezolizumab, and the majority of responses continued when these data were assessed," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "Durable responses are meaningful for people whose cancer has progressed on other medicines, and we plan to submit these results to global health authorities to bring this potential new option to people as soon as possible".

In February 2015, atezolizumab received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for the treatment of people whose NSCLC expresses PD-L1 and whose disease worsened during or after standard treatments (e.g. platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Roche is discussing these NSCLC data from POPLAR and BIRCH with the FDA as part of its Breakthrough Therapy Designation and with other health authorities around the world. Roche currently has seven ongoing phase III studies of atezolizumab alone or in combination with other medicines for various types of lung cancer.

About the POPLAR study
Full results of the POPLAR study will be presented by Johan Vansteenkiste, University Hospital Leuven, Leuven, Belgium (Abstract #14LBA) on Sunday, 27 September, 09:15 CET.

Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR)

POPLAR is a multicentre, open-label, randomised phase II study evaluating the efficacy and safety of atezolizumab compared with docetaxel in people with recurrent locally advanced or metastatic NSCLC. Patients were randomised to receive either atezolizumab 1200 mg intravenously every three weeks or docetaxel 75 mg/m2 intravenously every three weeks. Treatment with atezolizumab may have been continued as long as people were experiencing clinical benefit as assessed by the investigator, i.e. in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression. The study enrolled 287 people with previously treated, advanced NSCLC. The primary endpoint was overall survival (OS); secondary endpoints included progression free survival (PFS), ORR and safety. People were stratified by PD-L1 expression on tumour-infiltrating immune cells (ICs), histology and prior lines of therapy. PD-L1 expression was assessed for both tumour cells (TCs) and ICs; people were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Diagnostics.

About the BIRCH study
Interim results of the BIRCH study will be presented by Benjamin Besse, Institut Gustave Roussy, Villejuif France and Paris Sud University, France (Abstract #16LBA) on Sunday, 27 September, 09:35 Central European Time (CET).

Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic, PDL1-selected NSCLC

BIRCH is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed

PD-L1. PD-L1 expression was assessed for both TCs and tumour-infiltrating ICs with an investigational immunohistochemistry test (IHC) being developed by Roche Diagnostics. Eligibility criteria included people whose tumours were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200 mg intravenous dose of atezolizumab every three weeks. The primary endpoint of the study was the ORR assessed by independent review facility per RECIST v1.1. Secondary endpoints included duration of response, OS, PFS and safety.

About atezolizumab
Atezolizumab (anti-PDL1; MPDL3280A) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on TCs and tumour-infiltrating ICs, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PDL1, atezolizumab may activate T cells.

All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both TCs and tumour-infiltrating ICs. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancers.

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85 percent of all cases.