On June 29, 2016 Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer,reported it has entered into a cooperation agreement with the Max Delbrück Centre for Molecular Medicine in the Helmholtz Association (MDC), Berlin, and the Charité – Universitätsmedizin Berlin (Charité) (Press release, MediGene, JUN 29, 2016, View Source [SID:1234513618]).

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The partners will collaborate on a research project entitled "MageA1-TCR Gene Therapy of Multiple Myeloma (MAGEA1-TCR)", which is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF). The planned trial is currently the first study in Germany with patients with relapsed or refractory multiple myeloma that will equip a patient’s own T cells with tumor-specific T-cell receptors.

The clinical investigator-initiated phase I trial (IIT) is entitled "A Phase I study of MAGE-A1-specific TCR-transduced T cells in patients with relapsed/refractory multiple myeloma". As part of the study, the patient’s own T cells are activated and transduced with tumor antigen MAGE-A1-specific T-cell receptors using viral vectors. Following expansion, these modified cells are then re-administered to patients to destroy the cancer cells. The aim of this trial is to investigate the safety and tolerability of this innovative therapy approach.

Charité is responsible as the clinical partner for conducting the clinical trial and is a beneficiary of the public funding along with the MDC, which is in charge of the analytics and ensuring good manufacturing practices (GMP)[1]. Medigene is supporting both the MDC and Charité by handling regulatory affairs matters related to trial approval in addition to advising on the development of the analytics and GMP production. Medigene holds a first right of negotiation for an exclusive license to the study results for the commercial exploitation of the investigated TCR product candidate in multiple myeloma, and is additionally entitled to a undisclosed profit participation in the case of subsequent commercial exploitation by a third party.

Prof. Dr Dolores Schendel, CEO and CSO of Medigene and Project Leader in the collaborative project, comments on the signing of the contract: "We are delighted to be part of this first promising TCR project in Germany. The preparations required for this project will help pave the way for our own product candidates, which are also being developed for the treatment of diseases with a high unmet medical need."

Prof. Dr Antonio Pezzutto, Medical Director at Charité Campus Benjamin Franklin and Project Lead in the collaborative project, explains: "After signing this contract, we are pleased that the preparations for the clinical trial are in full swing. Our goal is to offer this new, innovative therapy to patients suffering from multiple myeloma with MAGE-A1 expression who do not or no longer respond to traditional chemotherapy."

Prof. Dr Blankenstein, Head of Molecular Immunology and Gene Therapy at the MDC, Director of the Institute of Immunology at Charité Campus Berlin Buch and Project Coordinator in the collaborative project, adds: "This allocation of funding will now enable us to enter the clinical development phase with our MAGE-A1 T-cell receptor and consequently bring German research in this field up to the highest international level. The MDC is proud to be playing an important role by carrying out the required analytics and ensuring GMP-compliant production of the living cells for this personalized treatment of cancer."

About TCR technology:
The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex-vivo). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.

Medigene’s technology for T-cell receptor-modified T cells is one of the company’s highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. The clinical development of Medigene has now begun preparing its own TCRs, and developing a library of recombinant T-cell receptors. Moreover, a good manufacturing practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established.

On June 29, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, reported the recommendation from the Independent Data Monitoring Committee (IDMC) on the interim analysis for Galena’s NeuVax (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial (Press release, Galena Biopharma, JUN 29, 2016, View Source [SID:1234513607]). On June 27, 2016, the IDMC recommended that the PRESENT trial be stopped due to futility. The letter is attached to the Form 8-K filed today and available on the Company’s website. This planned safety and futility interim analysis was triggered after 70 qualifying disease free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.

“We are extremely disappointed with the outcome of the PRESENT futility analysis,” said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. “On behalf of our entire company, I would like to thank all of the courageous patients and their families, investigators, study staff and independent committees who participated in the PRESENT study. To date, the trial has not been un-blinded other than by the IDMC, and we need to evaluate the data. We expect to host a conference call next week to provide a preliminary review of the PRESENT trial and an update on all of our immunotherapy and hematology clinical development programs.”

About PRESENT

PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) is an international, Phase 3 study to evaluate NeuVax plus GM-CSF versus placebo plus GM-CSF to prevent cancer recurrence. The trial is being run under a Special Protocol Assessment (SPA) granted by the U.S. Food and Drug Administration (FDA). PRESENT is targeting patients who are node positive, HER2 IHC 1+/2+, and HLA A2+ and/or A3+. The study is double blind, randomized 1:1, and is stratified by stage, type of surgery, hormone receptor status, and menopausal status. Galena enrolled a total of 758 patients, and the primary endpoint for the trial was disease free survival (DFS) upon reaching 141 events with 3 years minimum follow-up. Additional information on the trial can be found here and at clinicaltrials.gov identifier: NCT01479244.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

In addition to PRESENT, Galena has two breast cancer studies ongoing with NeuVax in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

On June 29, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, reported the recommendation from the Independent Data Monitoring Committee (IDMC) on the interim analysis for Galena’s NeuVax (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial (Press release, Galena Biopharma, JUN 29, 2016, View Source [SID:1234513607]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On June 27, 2016, the IDMC recommended that the PRESENT trial be stopped due to futility. The letter is attached to the Form 8-K filed today and available on the Company’s website. This planned safety and futility interim analysis was triggered after 70 qualifying disease free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.

"We are extremely disappointed with the outcome of the PRESENT futility analysis," said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. "On behalf of our entire company, I would like to thank all of the courageous patients and their families, investigators, study staff and independent committees who participated in the PRESENT study. To date, the trial has not been un-blinded other than by the IDMC, and we need to evaluate the data. We expect to host a conference call next week to provide a preliminary review of the PRESENT trial and an update on all of our immunotherapy and hematology clinical development programs."

About PRESENT

PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) is an international, Phase 3 study to evaluate NeuVax plus GM-CSF versus placebo plus GM-CSF to prevent cancer recurrence. The trial is being run under a Special Protocol Assessment (SPA) granted by the U.S. Food and Drug Administration (FDA). PRESENT is targeting patients who are node positive, HER2 IHC 1+/2+, and HLA A2+ and/or A3+. The study is double blind, randomized 1:1, and is stratified by stage, type of surgery, hormone receptor status, and menopausal status. Galena enrolled a total of 758 patients, and the primary endpoint for the trial was disease free survival (DFS) upon reaching 141 events with 3 years minimum follow-up. Additional information on the trial can be found here and at clinicaltrials.gov identifier: NCT01479244.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

In addition to PRESENT, Galena has two breast cancer studies ongoing with NeuVax in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

On June 29, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the Phase 3 NOVA trial of niraparib successfully achieved its primary endpoint of progression-free survival (PFS) (Press release, TESARO, JUN 29, 2016, View Source [SID:1234513606]). This trial demonstrated that niraparib significantly prolonged PFS compared to control among patients who are germline BRCA mutation (gBRCAmut) carriers, among patients who are not germline BRCA mutation (non-gBRCAmut) carriers but who have homologous recombination deficient (HRD) tumors as determined by the Myriad myChoice HRD test, and overall in patients who are not germline BRCA mutation carriers.

An infographic accompanying this release is available at:
View Source

Videos accompanying this release are available at:
View Source

View Source

NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. There is currently no therapy approved by the U.S. Food and Drug Administration for maintenance treatment of patients with recurrent ovarian cancer following response to platinum.

“We are extremely grateful to the patients, caregivers, and investigators who participated in the NOVA trial. The results of this study, which is the first successful, prospectively designed, randomized, well-controlled Phase 3 study of a PARP inhibitor, demonstrate that a single, daily, oral dose of niraparib is superior to control in prolonging PFS in women with recurrent ovarian cancer,” said Mary Lynne Hedley, Ph.D., President and COO of TESARO. “Importantly, these results show activity of niraparib in a population of ovarian cancer patients beyond those with germline BRCA mutations. In keeping with our mission of responsible drug development, NOVA was designed to define those patients most likely to benefit from niraparib treatment and, in so doing, optimize the benefit/risk profile for patients. We believe we have achieved that goal and look forward to presentation of the full data set from this study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress in October.”

Statistically Significant PFS Results in the gBRCAmut Cohort
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 0.27. The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p < 0.0001). Statistically Significant PFS Results in non-gBRCAmut Cohort for Patients with HRD Positive Tumors For patients who were not germline BRCA mutation carriers but whose tumors were determined to be HRD positive using the Myriad myChoice HRD test, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.38. The median PFS for patients with HRD-positive tumors who were treated with niraparib was 12.9 months, compared to 3.8 months for control (p < 0.0001). Statistically Significant PFS Results in the Overall non-gBRCAmut Cohort Niraparib also showed statistical significance in the overall non-germline BRCA mutant cohort, which included patients with both HRD-positive and HRD-negative tumors. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.45. The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p < 0.0001). The most common (≥10%) treatment-emergent grade 3/4 adverse events among all patients treated with niraparib were thrombocytopenia (28.3%), anemia (24.8%) and neutropenia (11.2%). Adverse events were generally managed via dose modifications. The discontinuation rate was 14.7% for niraparib treated patients and 2.2% for control. The rates of MDS/AML in the niraparib (1.3%) and control (1.2%) arms were similar. There were no deaths among patients during study treatment. "The majority of women who are diagnosed with advanced ovarian cancer will experience a relapse of their disease, even if they respond to their initial chemotherapy," said Dr. Tom Herzog, M.D., Clinical Director, University of Cincinnati Cancer Institute and Professor, Department of Obstetrics and Gynecology at the University of Cincinnati. "New treatment options are needed to extend the time in between cycles of platinum-based chemotherapy for these patients, and the results from the NOVA study suggest that niraparib could represent an important new treatment option for many patients with ovarian cancer." "While the identification of mutations in the BRCA genes was a significant advancement, ovarian cancer remains the deadliest of gynecologic cancers, and new diagnostic and therapeutic options are needed," said David Barley, Chief Executive Officer of the National Ovarian Cancer Coalition. "The results of the NOVA trial are encouraging for patients and their families, and we look forward to seeing the full results of this study this fall." About the Phase 3 NOVA Clinical Trial of Niraparib NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that planned to enroll 490 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). The non-gBRCAmut cohort included patients with HRD-positive tumors, including those with somatic BRCA mutations and other HR defects, and patients with 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 include patient-reported outcomes, chemotherapy-free interval length, PFS2, overall survival, and other measures of safety and tolerability. More information about this trial is available at View Source Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA or any other regulatory agencies. About Homologous Recombination Deficiency (HRD) Homologous recombination deficiency (HRD) is a defect in high-fidelity, double-strand DNA repair. HRD results from a variety of causes, including mutations in BRCA and other genes involved in DNA repair, as well as other unidentified causes. In cells with HRD, such as BRCA1 and BRCA2 mutant cells, lack of functional DNA repair pathways, including PARP, leads to irreparable double-strand breaks, genomic instability, and ultimately cell death. Because HRD-positive cells are sensitive to DNA-damaging processes, they are reliant upon proper DNA repair by other pathways, including PARP-dependent pathways. Comprehensive assessment of HRD status includes both tBRCA mutational analysis and assessment of genomic instability through the combined analysis of HRD biomarker components LOH, TAI, and LST. myChoiceHRD is a registered trademark of Myriad Genetics, Inc. About Niraparib Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three ongoing pivotal trials. 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 the Phase 3 trial in patients with ovarian cancer (the NOVA trial) as described above; a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial); and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus pembrolizumab and bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan. About Ovarian Cancer Approximately 22,000 women are diagnosed each year with ovarian cancer in the United States, and nearly 80% are diagnosed after the disease has become symptomatic and has progressed to a late stage. 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, 90% of patients will experience recurrence within two years. If approved, niraparib may address the difficult "watchful waiting" periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy.

On June 29, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the Phase 3 NOVA trial of niraparib successfully achieved its primary endpoint of progression-free survival (PFS) (Press release, TESARO, JUN 29, 2016, View Source [SID:1234513606]). This trial demonstrated that niraparib significantly prolonged PFS compared to control among patients who are germline BRCA mutation (gBRCAmut) carriers, among patients who are not germline BRCA mutation (non-gBRCAmut) carriers but who have homologous recombination deficient (HRD) tumors as determined by the Myriad myChoice HRD test, and overall in patients who are not germline BRCA mutation carriers.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

An infographic accompanying this release is available at:
View Source

Videos accompanying this release are available at:
View Source

View Source

NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. There is currently no therapy approved by the U.S. Food and Drug Administration for maintenance treatment of patients with recurrent ovarian cancer following response to platinum.

"We are extremely grateful to the patients, caregivers, and investigators who participated in the NOVA trial. The results of this study, which is the first successful, prospectively designed, randomized, well-controlled Phase 3 study of a PARP inhibitor, demonstrate that a single, daily, oral dose of niraparib is superior to control in prolonging PFS in women with recurrent ovarian cancer," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Importantly, these results show activity of niraparib in a population of ovarian cancer patients beyond those with germline BRCA mutations. In keeping with our mission of responsible drug development, NOVA was designed to define those patients most likely to benefit from niraparib treatment and, in so doing, optimize the benefit/risk profile for patients. We believe we have achieved that goal and look forward to presentation of the full data set from this study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress in October."

Statistically Significant PFS Results in the gBRCAmut Cohort
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 0.27. The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p < 0.0001).

Statistically Significant PFS Results in non-gBRCAmut Cohort for Patients with HRD Positive Tumors
For patients who were not germline BRCA mutation carriers but whose tumors were determined to be HRD positive using the Myriad myChoice HRD test, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.38. The median PFS for patients with HRD-positive tumors who were treated with niraparib was 12.9 months, compared to 3.8 months for control (p < 0.0001).

Statistically Significant PFS Results in the Overall non-gBRCAmut Cohort
Niraparib also showed statistical significance in the overall non-germline BRCA mutant cohort, which included patients with both HRD-positive and HRD-negative tumors. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.45. The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p < 0.0001).

The most common (≥10%) treatment-emergent grade 3/4 adverse events among all patients treated with niraparib were thrombocytopenia (28.3%), anemia (24.8%) and neutropenia (11.2%). Adverse events were generally managed via dose modifications. The discontinuation rate was 14.7% for niraparib treated patients and 2.2% for control. The rates of MDS/AML in the niraparib (1.3%) and control (1.2%) arms were similar. There were no deaths among patients during study treatment.

"The majority of women who are diagnosed with advanced ovarian cancer will experience a relapse of their disease, even if they respond to their initial chemotherapy," said Dr. Tom Herzog, M.D., Clinical Director, University of Cincinnati Cancer Institute and Professor, Department of Obstetrics and Gynecology at the University of Cincinnati. "New treatment options are needed to extend the time in between cycles of platinum-based chemotherapy for these patients, and the results from the NOVA study suggest that niraparib could represent an important new treatment option for many patients with ovarian cancer."

"While the identification of mutations in the BRCA genes was a significant advancement, ovarian cancer remains the deadliest of gynecologic cancers, and new diagnostic and therapeutic options are needed," said David Barley, Chief Executive Officer of the National Ovarian Cancer Coalition. "The results of the NOVA trial are encouraging for patients and their families, and we look forward to seeing the full results of this study this fall."

About the Phase 3 NOVA Clinical Trial of Niraparib
NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that planned to enroll 490 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). The non-gBRCAmut cohort included patients with HRD-positive tumors, including those with somatic BRCA mutations and other HR defects, and patients with 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 include patient-reported outcomes, chemotherapy-free interval length, PFS2, overall survival, and other measures of safety and tolerability. More information about this trial is available at View Source

Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA or any other regulatory agencies.

About Homologous Recombination Deficiency (HRD)
Homologous recombination deficiency (HRD) is a defect in high-fidelity, double-strand DNA repair. HRD results from a variety of causes, including mutations in BRCA and other genes involved in DNA repair, as well as other unidentified causes. In cells with HRD, such as BRCA1 and BRCA2 mutant cells, lack of functional DNA repair pathways, including PARP, leads to irreparable double-strand breaks, genomic instability, and ultimately cell death. Because HRD-positive cells are sensitive to DNA-damaging processes, they are reliant upon proper DNA repair by other pathways, including PARP-dependent pathways.

Comprehensive assessment of HRD status includes both tBRCA mutational analysis and assessment of genomic instability through the combined analysis of HRD biomarker components LOH, TAI, and LST. myChoiceHRD is a registered trademark of Myriad Genetics, Inc.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three ongoing pivotal trials. 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 the Phase 3 trial in patients with ovarian cancer (the NOVA trial) as described above; a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial); and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus pembrolizumab and bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the United States, and nearly 80% are diagnosed after the disease has become symptomatic and has progressed to a late stage. 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, 90% of patients will experience recurrence within two years. If approved, niraparib may address the difficult "watchful waiting" periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy.