On December 5, 2017 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (Oncolytics or the Company), a biotech company developing REOLYSIN, also known as pelareorep, an intravenously delivered immuno-oncolytic virus that activates the innate and adaptive immune systems to turn ‘cold’ tumors ‘hot’, reported that the company has received a favorable Final Advice Letter from the European Medicines Agency (EMA) (Press release, Oncolytics Biotech, DEC 5, 2017, View Source [SID1234522394]). The Letter refers to the proposed use of pelareorep in combination with paclitaxel, for the treatment of hormone receptor positive, HER2 receptor negative (HR+/HER2-) metastatic breast cancer patients in a pivotal phase 3 registration study and suggests that a single 400-patient study may be acceptable to form the basis of a Marketing Authorization Application (MAA) in Europe.

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"The EMA’s feedback and Final Advice Letter are very much inline with the feedback and advice we received from the FDA in September and adds to the support we have for our proposed target patient population of HR positive/HER2 negative metastatic breast cancer patients for the registration study," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "Our statistically significant and clinically compelling overall survival data, Fast Track designation and clear guidance from the FDA and EMA allow us to focus on the completion of the adaptive study design that will include approximately four hundred patients with a pre-determined interim analysis at two hundred patients. Furthermore, the EMA provided guidance that if the study achieves its primary endpoint, it may form the basis of a Marketing Authorization Application for commercialization in Europe. The design of the study, feedback from both the FDA and EMA and our recently announced partnership with Adlai Nortye will also drive our ongoing partnering process."

Oncolytics’ proposed target population for its phase 3 study of pelareorep is patients with HR+/HER2- mBC, which represents approximately 73 percent of metastatic breast cancer cases that have limited treatment options that offer survival benefit. Details of the pivotal phase 3 registration study will be made available following evaluation and completion of discussions with clinical advisors and potentially partners.

About Metastatic Breast Cancer
Metastatic breast cancer, also known as advanced or Stage 4 breast cancer, has spread to other parts of the body. Most commonly the lungs, liver, bones or brain. The disease affects over 154,000 women in the United States and according to the American Cancer Society, has a five-year survival rate of just 22 percent. Significantly lower than stage 3, with a five-year relative survival rate of 72 percent and stage 2, with a five-year survival rate over 90 percent.

About REOLYSIN/Pelareorep
REOLYSIN, also known as pelareorep, is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers.

On December 5, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY): reported that following close consultation and agreement on study modifications with the U.S. Food and Drug Administration (FDA), the partial clinical holds placed on the Phase Ib and Phase Ib/II studies evaluating TECENTRIQ in combination with an immunomodulatory medicine (IMiD) in relapsed/refractory multiple myeloma and relapsed/refractory follicular lymphoma have been lifted (Press release, Hoffmann-La Roche, DEC 5, 2017, View Source [SID1234522368]). The studies will continue in accordance with the protocol amendments agreed upon by the FDA.

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The studies had been placed on partial clinical hold as part of an FDA evaluation of all ongoing blood cancer trials, investigating PD-1/PD-L1 inhibitors in combination with an IMiD to determine if there was a class-wide (PD-1/PD-L1 inhibitor) concern in multiple myeloma/blood cancers, or a specific concern with certain combinations with IMiDs. The FDA evaluation was prompted by interim data from clinical trials evaluating pembrolizumab in combination with either lenalidomide or pomalidomide in multiple myeloma.

On December 5, 2017 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has granted full approval for Avastin (bevacizumab) for the treatment of adults with glioblastoma that progressed following prior therapy (referred to as recurrent disease) (Press release, Genentech, DEC 5, 2017, View Source [SID1234522413]). Avastin was previously granted provisional approval in this setting under the FDA’s accelerated approval program.

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"Glioblastoma is the most common and aggressive form of brain cancer and can be very difficult to treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Delaying disease progression and reducing the need for corticosteroids over the course of treatment are considered important goals for those impacted by this devastating disease where patients have limited treatment options."

This conversion to full approval was based on the totality of evidence of Avastin in glioblastoma, including data from the Phase III EORTC 26101 study. Avastin is now approved in the United States for nine distinct uses across six different types of cancer.

About the EORTC 26101 Study

EORTC 26101 is an independent Phase III, multicenter, randomized, open-label trial, conducted by the European Organization for Research and Treatment of Cancer (EORTC), that evaluated the addition of Avastin to lomustine chemotherapy in 432 patients with previously treated glioblastoma. The primary endpoint of the study was overall survival (OS), and progression-free survival (PFS) as assessed by investigator and overall response rate (ORR) were key secondary endpoints. Results showed the following:

There was no significant increase in OS with Avastin-based treatment (HR=0.91, p=0.4578).
As the primary endpoint was not met, all secondary endpoints should be considered descriptive only.
Avastin-based treatment increased the time to disease progression or death compared to chemotherapy alone (median PFS: 4.2 months vs. 1.5 months, HR=0.52, 95% CI: 0.41-0.64).
Among people taking corticosteroids at baseline (50 percent), more people were able to completely stop intake of corticosteroids while on treatment in the Avastin arm compared to the control arm (23 percent vs. 12 percent).
In the Avastin with lomustine arm, 22 percent of people discontinued treatment due to adverse reactions compared with 10 percent of people in the lomustine arm.
Adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications.
About Glioblastoma

Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumor (a tumor that originates in the brain), and represents nearly one-fourth of all primary brain tumors and three-fourths of all malignant tumors. Glioblastoma (or glioblastoma multiforme) is the most common and the most aggressive type of glioma, accounting for more than half of all gliomas. It is estimated that more than 12,300 people will be diagnosed with glioblastoma in the United States in 2017.

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 1.5 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit View Source for more information.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).

Avastin Indications:

Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy after cancer progresses following a first-line treatment that includes Avastin.
Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body.
Advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel in people who have not received chemotherapy for their advanced disease.
Metastatic kidney cancer (mRCC) when used with interferon alfa.
Glioblastoma (GBM) in adult patients whose cancer has progressed after prior treatment (recurrent or rGBM).
Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan is approved to treat persistent, recurrent, or metastatic cancer of the cervix.
Recurrent ovarian cancer (rOC) . Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (prOC) in women who received no more than two prior chemotherapy treatments. Avastin, either in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by Avastin alone, is approved for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (psOC).

Possible serious side effects

Everyone reacts differently to Avastin therapy. So it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Their doctor will stop treatment if any serious side effects occur.Patients should talk to their doctor if there are any signs of these side effects.

Most serious side effects (not common, but sometimes fatal):

GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgicalwounds are fully healed
Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor
Other possible serious side effects

Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
Infusion reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness
Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

High blood pressure
Too much protein in the urine
Nosebleeds
Rectal bleeding
Back pain
Headache
Taste change
Dry skin
Inflammation of the skin
Inflammation of the nose
Watery eyes
Avastin is not for everyone

Patients should talk to their doctor if they are:

Undergoing surgery . Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
Pregnant or think they are pregnant . Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children.
Breastfeeding . Breastfeeding while on Avastin may harm the baby and is therefore not recommended
Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source . Report side effects to Genentech at (888) 835-2555.

For full Prescribing Information on Avastin please visit View Source .

On December 5, 2017 At the American Society of Hematology (ASH) (Free ASH Whitepaper)’s 59th Annual Meeting and Exposition in Atlanta, Georgia, researcher Gustavo Milone, MD, and his team reported that will present a study that investigates the post-marketing trends of Novex, a biosimilar rituximab that has been approved in Argentina for the same indications as the reference product (MabThera, Rituxan) (Press release, mAbxience, DEC 5, 2017, View Source [SID1234594760]).1 Since Novex’s commercial launch, the first national pharmacovigilance plan for a biosimilar monoclonal antibody has been implemented, and data from this post-marketing surveillance show that, in terms of tolerability, this biosimilar has a similar safety profile to that of the reference product.

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In order to determine deviations from expected frequencies of adverse events (AEs), a prospective treatment registry for the biosimilar was implemented from the start of its commercialization on November 26, 2014. Data in the study are reported until June 30, 2017. Physicians, 180 in total, tracked age, gender, indication, dose, dose frequency, and date of treatment initiation and finalization for each patient receiving the biosimilar.

The study comprised the records of 525 patients who had at least 1 follow-up. The majority of patients were female (52%), the mean age was 63.3 years (range, 10-90), and most patients received the biosimilar rituximab for hematological disease (91.2% of cases). The treatment duration ranged from 154 to 309 days, with the number of treatment cycles varying from 1 to 12. Individual Case Safety Reports (ICSRs) were collected from 24 patients with 29 AEs.

The most frequently reported AEs were:

Acute infusion-related reaction (14)
Arrhythmia (3)
Pneumonia (2)
Stroke (2)
The researchers noted that 41 treatments with rituximab were initiated before the launch of the product; assuming treatment began with MabThera, these 41 treatments imply switching to the biosimilar from the reference.

Researchers investigating data from the post-marketing surveillance found a similar incidence of AEs after the use of rituximab biosimilar when compared to the published data of the reference product. Thus, in terms of tolerability, the biosimilar has a similar safety profile compared with its reference.

On December 5, 2017 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company dedicated to the development of next-generation multifunctional biotherapeutics, reported the completed dose escalation portion of its Phase 1 study of ZW25, a novel Azymetric bispecific antibody targeting two distinct domains of the HER2 receptor (Press release, Zymeworks, DEC 5, 2017, View Source [SID1234522372]). The HER2–mediated signaling pathway is believed to contribute to tumor growth in a number of cancers.

A total of 22 patients have been enrolled in the study, including 11 with breast cancer, eight with gastric, gastroesophageal junction, or esophageal (GE) cancer, and three with other HER2-expressing cancers. Part one of the multi-part study was a standard dose escalation where patients received ZW25 either weekly at 5 mg/kg (n=3), 10 mg/kg (n=6), or 15 mg/kg (n=7) or bi-weekly (once every two weeks) at 20 mg/kg (n=6) in cycles of four weeks each.

Study Highlights:

Six Partial Responses (PR) were observed across all dosing groups including two new PRs from the 20 mg/kg bi-weekly cohort.

Clinical benefit (Confirmed PR or stable disease (SD) ≥ 6 months) of single agent ZW25 observed in heavily pretreated HER2-high breast and GE cancer patients.

Breast cancer patients received a median of six prior HER2-targeted regimens for metastatic disease; partial response in 56% (5/9) of breast cancer patients with measurable disease, with 89% (8/9) experiencing a decrease in target lesions.

Three HER2-high GE cancer patients with measurable disease showed tumor shrinkage, including one Confirmed PR (71% decrease in target lesions) and one SD for > 6 months.

ZW25 was well-tolerated at all doses and schedules, with the most common adverse events being diarrhea, infusion reactions, or nausea, all Grade 1 or 2 in severity.

The dose escalation portion of the Phase 1 trial is complete and enrollment in the expansion cohorts is underway.
Seventy-nine percent of breast and GE cancer patients with measurable disease (11/14) had a decrease in target lesions per RECIST criteria. The best overall response (BOR) in 17 response-evaluable (defined as undergoing at least one tumor restaging) breast and GE cancer patients was six PR (35%), three SD (18%) and eight progressive disease (PD; 47%).

"The expanding dataset continue to show responses and durable disease control with both weekly and every other week dosing and demonstrate the potential of ZW25 to address unmet need across multiple indications," said Dr. Diana Hausman, Chief Medical Officer of Zymeworks. "We are seeing meaningful clinical benefit with single agent treatment in breast and gastric cancer patients who have progressive disease after numerous standard of care regimens. These early results, while impressive in their own right, are also distinct from other investigational agents being evaluated in refractory HER2-expressing cancer patients and support the continued evaluation of ZW25 both as a single agent and in combination with other cancer therapeutics."

Of the eleven breast cancer patients, all were HER2-high and had received a median of six prior HER2-targeted regimens for metastatic disease including trastuzumab (n=11), T-DM1 (n=11), pertuzumab (n=9), and lapatinib (n=7) as well as other investigational agents. The BOR in these heavily pretreated patients was five PR (45%), two SD (18%), and three PD (27%), for an overall disease control rate (Complete Response, PR, or SD) of 64%. At least one PR was observed in every dosing group.

Of the eight GE patients, six were evaluable for response, and had received a median of four prior systemic regimens, including trastuzumab in all patients. Three of five patients with measurable disease had a decrease in tumor size, including one patient continuing on treatment with a Confirmed PR and 71% decrease in target lesions, as well as a second patient with SD for over 6 months.

"There is an ongoing need for novel treatments for patients who have exhausted available options for their HER2-expressing cancers," said Dr. Erika Hamilton, Director of the Breast Cancer and Gynecologic Cancer Research Program at Sarah Cannon Research Institute in Nashville, Tennessee. "The preliminary anti-tumor activity and tolerability we have seen with single agent ZW25 has been encouraging. We are excited to be enrolling patients in the expansion cohort portion of this study."

Enrollment is underway for the second part of the study utilizing ZW25 every other week at 20 mg/kg in four expansion cohorts spanning HER2-high breast, HER2-high gastric, HER2-intermediate breast and other HER2-gene amplified cancers.

"The dose escalation portion of the Phase 1 trial has been a success, demonstrating the tolerability and single agent anti-tumor activity of ZW25," said Dr. Ali Tehrani, President and CEO of Zymeworks. "These data bring us one step closer to initiating a single agent registrational trial with the goal of submitting an initial Biologics License Application (BLA) for ZW25 in 2021. We plan to provide an update on the expansion cohort portion of the trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in 2018."

The poster will be formally presented on Friday December 8th from 5:00-7:00pm CT at the San Antonio Breast Cancer Symposium and is available through their website or through the Investor page of Zymeworks’ website at View Source

ZW25 Phase 1 Clinical Trial Details

The dose escalation portion of the study enrolled 22 patients with HER2-expressing cancers (either HER2 IHC 1+, 2+ or 3+, or FISH-positive) whose cancer had progressed after treatment with all therapies known to confer clinical benefit. HER2 status was assessed in archived or fresh biopsies locally and at a central laboratory. Patients with HER2-high breast cancer (HER2 IHC 3+ or IHC2+ and FISH-positive) had to have received previous treatment with trastuzumab, pertuzumab, and T-DM1. Patients with HER2-high gastric or gastroesophageal cancers had to have been previously treated with trastuzumab. Patients could have measurable or non-measurable tumor lesions per RECIST 1.1. Patients with known active brain metastases were excluded from the study. Patients were assessed during treatment for safety, including changes in cardiac function, tumor response per RECIST 1.1 every 8 weeks, ZW25 drug levels, and potential development of anti-drug antibodies. No dose-limiting toxicities were seen at any dose level or schedule. The most common adverse events were diarrhea, infusion reactions, or nausea, all Grade 1 or 2 in severity. There were no treatment-related serious adverse events, cardiac events or decreases in left ventricular ejection fraction.

About ZW25

ZW25 is Zymeworks’ lead product candidate currently being evaluated in a Phase 1 clinical trial in the United States. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to significant anti-tumor activity in preclinical models of HER2-expressing cancer. Zymeworks is developing ZW25 as a best-in-class HER2-targeted treatment option for patients with any solid tumor that expresses HER2.