On April 19, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported the initiation of a Phase 2 clinical trial of its prostate cancer immunotherapy candidate, PROSTVAC (rilimogene), in combination treatment with YERVOY (ipilimumab) and/or OPDIVO (nivolumab), both of which are immune checkpoint inhibitors from Bristol-Myers Squibb, as neoadjuvant therapy in patients with localized prostate cancer (Press release, Bavarian Nordic, APR 19, 2017, View Source [SID1234518623]).

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A lead-in stage will evaluate the safety of the combination of all three drugs in 10 patients with castration-resistant prostate cancer, followed by enrollment of up to 55 patients with localized prostate cancer in three cohorts, who will receive PROSTVAC in combination with either ipilimumab or nivolumab, or a combination of all three drugs prior to undergoing radical prostatectomy. The primary endpoint of the study is to evaluate and compare changes in T cell infiltration in the tumor after neoadjuvant treatment across the three different cohorts. The principal investigator of the study is James L. Gulley, MD, Senior Investigator, Center for Cancer Research, part of the National Cancer Institute (NCI), and the sponsor of the study. Detailed information on the trial can be found at View Source

"There are now eleven ongoing studies of PROSTVAC across various stages of prostate cancer. In recent years, there has been a growing interest in the evaluation of the immunotherapy candidate in earlier disease stages, where the cancer has not yet spread beyond the prostate. We are excited to learn more about the potential of PROSTVAC for treating this population, and to evaluate the potential synergistic effects of combining the vaccine with checkpoint inhibitors, as we believe PROSTVAC may enhance the clinical activity of these drugs," said Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic.

This is the second trial conducted in collaboration with Bristol-Myers Squibb. The first trial was initiated in October 2016, and is investigating the combination treatment of PROSTVAC and ipilimumab at the University of California, San Francisco (UCSF), also in a neoadjuvant setting.

For patients interested in enrolling in this clinical trial, please call NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or see the website: View Source and search for NCT02933255.

About PROSTVAC
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec or "rilimogene") is a prostate specific antigen (PSA)-targeted immunotherapy candidate designed to enhance or stimulate the body’s immune response, specifically T cells that will target and kill prostate cancer cells, altering the course of the disease and improving overall survival (OS) of patients with prostate cancer. A robust data package has been established that includes 19 ongoing or completed clinical studies, comprising more than 2,000 patients of which more than 1,100 patients have been actively treated with PROSTVAC, which has been generally well-tolerated. A pivotal Phase 3 clinical trial in 1,297 patients, designed to determine if PROSTVAC extends the overall survival for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) has completed enrollment and top-line data are anticipated in 2017.

The combination of PROSTVAC and ipilimumab was previously investigated in an NCI-sponsored Phase 1 trial in mCRPC patients, indicating improved survival for the treatment regimen when compared to the predicted survival (J Clin Oncol 33, 2015 (suppl 7; abstr 172)). This improved effect is believed to be due to PROSTVAC’s ability to stimulate an anti-prostate cancer immune response combined with the ability of checkpoint inhibitors to make the anti-cancer immune response more effective.

PROSTVAC is being developed in collaboration with the Center for Cancer Research, part of the intramural research program of the National Cancer Institute under a Cooperative Research and Development Agreement.

More information available at /pipeline/prostvac.aspx.

About ipilimumab and nivolumab
Ipilimumab and nivolumab are immune checkpoint inhibitors developed and marketed by Bristol-Myers Squibb. Ipilimumab is a CTLA-4 antibody, which is approved by the FDA for the treatment of melanoma. Nivolumab is a PD-1 antibody, which is approved for the treatment of patients with NSCLC in the second line setting, among other indications. These immune checkpoint inhibitors work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash and/or enhance pre-existing anti-cancer immune responses.

On April 19, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that ZEJULA (niraparib), an oral, once-daily poly(ADP-ribose) polymerase (PARP) inhibitor, is now available by prescription in the United States (Press release, TESARO, APR 19, 2017, View Source [SID1234518621]). The U.S. Food and Drug Administration (FDA) approved ZEJULA on March 27, 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response (CR or PR) to platinum-based chemotherapy. The National Comprehensive Cancer Network (NCCN) recently added ZEJULA to the NCCN Clinical Practice Guidelines in Oncology Ovarian Cancer version 1.2017—April 12, 2017—as maintenance therapy for patients with platinum-sensitive disease who are in partial or complete response after completion of two or more lines of platinum-based therapy.

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"TESARO is committed to the responsible development and commercialization of transformative therapies for people bravely facing cancer, and we are proud to bring ZEJULA to women who until today had limited treatment options," said Lonnie Moulder, CEO of TESARO. "Increasing progression-free survival after platinum therapy is a truly meaningful benefit for patients and their families, and the once-daily, individualized dosing of ZEJULA allows healthcare providers to ensure the optimal dose per patient without compromising efficacy. We are committed to ensuring access for patients through TOGETHER with TESARO, our patient assistance program for ZEJULA, and we look forward to delivering this important new treatment option to patients and their caregivers."

ZEJULA is the only PARP inhibitor that has demonstrated a clinically meaningful increase in progression-free survival (PFS) in women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status, in a randomized, prospectively designed Phase 3 clinical trial. ZEJULA offers oral, once-daily dosing, enabling convenient administration for maintenance treatment. FDA approval of ZEJULA is based upon data from the international Phase 3 ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled study that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by robust, unbiased, blinded central review, to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with and without germline BRCA mutations as compared to control. Treatment with ZEJULA reduced the risk of disease progression or death by 74% in patients with germline BRCA mutations (HR 0.26) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

The most common grade 3/4 adverse reactions to ZEJULA in the NOVA trial included thrombocytopenia (29%), anemia (25%), neutropenia (20%), and hypertension (9%). The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3.3%, 1.9% and 1.4% of patients, respectively. Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low; approximately <1% after month 2. Please see the "Select Important Safety Information" below for warnings, precautions and adverse events.

"Women with recurrent ovarian cancer often experience considerable fear and anxiety about future recurrences," said Audra Moran, President and CEO of Ovarian Cancer Research Fund Alliance. "ZEJULA may offer patients and their families a treatment option during this stressful period. The ovarian cancer community is eager for new treatment options, and we are glad that ZEJULA will be available to women that have completed their platinum-based chemotherapy."

The Wholesale Acquisition Cost (WAC) of ZEJULA is $9,833 for a one-month supply of ZEJULA at a dose of 200 milligrams once per day, the most commonly administered dose over the course of the Phase 3 NOVA clinical trial. The approved starting dose of ZEJULA is 300 milligrams once per day.

TESARO is committed to ensuring access to ZEJULA. The Company’s patient assistance program, TOGETHER with TESARO, is a reflection of TESARO’s commitment to the patient community and includes comprehensive services such as commercial copay assistance, assistance for the uninsured or underinsured, and access to other organizations that support ovarian cancer patients, among others.

About TOGETHER with TESARO
TOGETHER with TESARO is a patient resource program dedicated to supporting people living with cancer. The program assists with access issues, so that patients with cancer can be free to focus on treatment goals and simply living life. It provides a full suite of services to meet each patient’s needs and individual experience. A team of access and affordability experts is available to help oncology practices and patients gain access to the medication they require. TOGETHER with TESARO will continue to evolve and grow to meet provider and patient needs. For more information, please visit www.togetherwithtesaro.com or call 1-844-2TESARO (1-844-283-7276).

About Ovarian Cancer
Approximately 22,000 women are diagnosed with ovarian cancer each year in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth-most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. Per NCCN guidelines, BRCA testing and genetic counseling remain important components of the medical workup for all patients upon a diagnosis with ovarian cancer.

About the ZEJULA (Niraparib) ENGOT-OV16/NOVA Clinical Trial
ENGOT-OV16/NOVA was a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled 553 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. Patients were enrolled into one of two independent cohorts based on germline BRCA mutation status. One cohort enrolled patients who were germline BRCA mutation carriers (gBRCAmut), and the second cohort enrolled patients who were not germline BRCA mutation carriers (non-gBRCAmut) and included patients with HRD-positive and HRD-negative tumors. Within each cohort, patients were randomized 2:1 to receive niraparib or placebo and were treated continuously with placebo or 300 milligrams of niraparib, dosed as three 100 milligram tablets once per day, until progression. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included patient-reported outcomes, chemotherapy-free interval length, PFS 2, overall survival, and other measures of safety and tolerability. More information about this trial is available at View Source

Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.26 (95% CI, 0.173-0.410). The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p<0.0001). Niraparib also showed statistical significance for patients in the non-germline BRCA mutant cohort. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.45 (95% CI, 0.338-0.607). The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p<0.0001). Secondary endpoint analyses, including chemotherapy-free interval, time to first subsequent treatment, and PFS 2 were all statistically significant and favored niraparib over control for patients in both the gBRCAmut and non-gBRCAmut cohorts. Patient-reported outcome results from validated survey tools indicated that niraparib-treated patients reported no difference from control in measures associated with quality of life.

The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen on October 8, 2016 by Dr. Mansoor Raza Mirza, M.D., Medical Director of the Nordic Society of Gynecologic Oncology (NSGO) and principal investigator. These data were simultaneously published in the New England Journal of Medicine.

Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain/distension, mucositis/stomatitis, diarrhea, fatigue/asthenia, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash and hypertension.

Please see full Prescribing Information for additional Safety Information at www.zejula.com.

Additional Clinical Trials of Niraparib
TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients who have received first-line treatment for ovarian cancer (the PRIMA trial) and a registrational Phase 2 trial in patients who have received multiple lines of treatment for ovarian cancer (the QUADRA trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab (the TOPACIO trial) and niraparib plus bevacizumab (the AVANOVA trial).

Additional trials of niraparib in ovarian, breast and lung cancers are planned. The studies will assess the effect of niraparib alone and in combination with other therapies, such as bevacizumab and an anti-PD-1 antibody, in a variety of treatment settings.

Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

About ZEJULA (Niraparib)
ZEJULA is an oral, once-daily poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the U.S. for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The National Comprehensive Cancer Network (NCCN) recently added ZEJULA to the NCCN Clinical Practice Guidelines in Oncology Ovarian Cancer version 1.2017—April 12, 2017—as maintenance therapy for patients with platinum-sensitive disease who are in partial or complete response after completion of 2 or more lines of platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

On April 18, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that the Company will present new preclinical data on SY-1425, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase 2 clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, APR 19, 2017, View Source [SID1234518617]). These data were selected for oral presentation during a plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Hematologic Malignancies: Translating Discoveries to Novel Therapies conference taking place from May 6-9 in Boston.

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Details on the plenary talk and corresponding poster presentation are as follows:

Presentation Title: SY-1425 (tamibarotene), a potent and selective RARα agonist, induces changes in the transcriptional regulatory circuit of AML cells leading to differentiation
Presenter: Christopher Fiore, Ph.D., Scientist, Syros Pharmaceuticals

Date & Time of Plenary Session: Sunday, May 7, from 10:30 a.m. – 1 p.m.
Plenary Session 3: Chemical Biology
Location: Westin Boston Waterfront, Harbor Ballroom 3

Date & Time of Poster Presentation: Sunday, May 7, from 1 – 3 p.m.
Location: Westin Boston Waterfront, Harbor Ballroom 1-2, Poster Board Number 06

On April 19, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported issuance of a U.S. patent for KO-947, its drug candidate targeting extracellular-signal-regulated kinases (ERK) (Press release, Kura Oncology, APR 19, 2017, View Source [SID1234518614]). The new patent, U.S. 9,624,228, entitled "Inhibitors of ERK and Methods of Use," covers KO-947 and structurally-related compounds as well as methods of using the compounds for the treatment of diseases including cancer.

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"We believe KO-947 holds much promise as a potential therapeutic, and we were pleased to have advanced it into Phase 1 clinical testing earlier this month," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "Issuance of this composition of matter patent is an important development for Kura and the program."

About KO-947

KO-947 is a potent and selective small molecule ERK1/2 inhibitor. KO-947 exhibits potent anti-proliferative activity across a broad panel of tumor cell lines with mutations in BRAF, NRAS or KRAS and demonstrates prolonged pathway inhibition, both in vitro and in vivo. Durable tumor regression has been observed with KO-947 in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations.