On August 23, 2017 Amgen (NASDAQ:AMGN) reported that results from an overall survival (OS) analysis of the Phase 3 head-to-head ENDEAVOR trial were published online first in The Lancet Oncology (Press release, Amgen, AUG 23, 2017, View Source [SID1234520305]). Data showed that KYPROLIS (carfilzomib) administered at 56 mg/m2 twice weekly and dexamethasone (Kd56) reduced the risk of death by 21 percent over Velcade (bortezomib) and dexamethasone (Vd), resulting in a 7.6 month OS benefit (median OS 47.6 months for Kd56 versus 40.0 for Vd, HR=0.79; p=0.01). The OS benefit was consistent regardless of prior Velcade therapy (HR=0.75 for no prior Velcade; HR=0.84 for prior Velcade). This Kd56 regimen is already approved in the U.S., European Union and other countries based on the primary analysis of progression-free survival (PFS) in the ENDEAVOR study.

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"These results showed KYPROLIS and dexamethasone significantly reduced the risk of death compared to Velcade and dexamethasone in patients with relapsed or refractory multiple myeloma," said study co-author and investigator Meletios A. Dimopoulos, M.D., professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine. "These results support the use of KYPROLIS and dexamethasone as a standard of care for multiple myeloma patients at first relapse."

"In recent years, few clinical trials have demonstrated overall survival benefits in patients with relapsed or refractory multiple myeloma," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "In ENDEAVOR, the only head-to-head trial comparing proteasome inhibitors, KYPROLIS showed a statistically significant overall survival benefit of 7.6 months over Velcade. These results published today in The Lancet Oncology support KYPROLIS as a superior proteasome inhibitor in relapsed multiple myeloma patients. We’ve shared these data with regulatory agencies in the U.S. and Europe to support a potential label update."

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. Notably, rates of grade 2 or higher peripheral neuropathy, a frequent dose-limiting toxicity of Velcade, were five-times lower in patients receiving Kd56 versus patients receiving Vd (7 percent versus 35 percent, respectively). The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

As previously published in The Lancet Oncology, patients treated with Kd56 also achieved PFS of 18.7 months compared to 9.4 months in those receiving Vd, meeting the primary endpoint of the study (HR=0.53; 95 percent CI: 0.44 – 0.65; p<0.0001).

Since its approval in 2012, KYPROLIS has been prescribed to over 50,000 patients worldwide. The KYPROLIS clinical program continues to focus on providing solutions for physicians and patients in treating this frequently relapsing and difficult-to-treat cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

About ENDEAVOR
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kd56 versus Vd in patients whose multiple myeloma has relapsed after at least one, but not more than three, prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

Patients received treatment until progression with KYPROLIS as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For Cycle 1 only, KYPROLIS was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 Cycle 1 onwards. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of bortezomib. More than 75 percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide.

For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866 or the News Release section of Amgen.com.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and very aggressive disease that accounts for approximately one percent of all cancers.2,3 In the U.S., there are nearly 95,000 people living with, or in remission from, multiple myeloma.4 Approximately 30,330 Americans are diagnosed with multiple myeloma each year and 12,650 patient deaths are reported on an annual basis.4

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.5 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.5 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.5,6

KYPROLIS is approved in the U.S. for the following:

In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Canada, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.
Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.
Acute Renal Failure

Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with KYPROLIS. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus dexamethasone.
Infusion Reactions

Infusion reactions, including life-threatening reactions, have occurred in patients receiving KYPROLIS.
Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.

Hemorrhage

Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant‐ineligible Patients

In a clinical trial of transplant‐ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KYPROLIS in combination with melphalan and prednisone is not indicated for transplant‐ineligible patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.
ADVERSE REACTIONS

The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.
The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.
Please see full prescribing information at www.kyprolis.com.

On August 23, 2017 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that patient enrollment has been completed in the Company’s Phase 2b METRIC study of glembatumumab vedotin in patients with metastatic triple negative breast cancers that overexpress gpNMB (Press release, Celldex Therapeutics, AUG 23, 2017, View Source [SID1234520304]). Glembatumumab vedotin is an antibody-drug conjugate that targets and binds to gpNMB, a protein expressed by multiple tumor types, including breast cancer. Overexpression of gpNMB has been shown to promote the migration, invasion and metastasis of the disease. It is highly expressed in triple negative breast cancers, where it is associated with increased risk of recurrence and poor clinical outcome.

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"We are extremely grateful to the METRIC investigators and the patients and families who supported this trial," said Anthony Marucci, Co-Founder, President and Chief Executive Officer of Celldex Therapeutics. "Patients with triple negative breast cancer have very limited treatment options. We believe glemba holds significant promise as a potential new targeted treatment for patients with this devastating disease and look forward to topline data, likely in the second quarter of 2018."

The METRIC study is a randomized Phase 2b study of glembatumumab vedotin in patients with metastatic triple negative breast cancers that overexpress gpNMB. In this indication, overexpression is defined as greater than or equal to 25% of tumor cells testing positive for gpNMB. Patients are randomized 2 to 1 to either glembatumumab vedotin or to capecitabine, also known by the tradename Xeloda, as a comparator. In total, 327 patients were enrolled into METRIC. The primary endpoint of the study is progression-free survival (PFS), which is defined as the time from randomization to the earlier of disease progression or death due to any cause. The study calls for 203 progression events for evaluation of the primary endpoint, which will be assessed based on an independent, central reading of patient scans. The sum of the data, including the secondary endpoints of response rate, overall survival, duration of response and safety, will be important in assessing clinical benefit. The Company projects that topline primary endpoint data should be available in the second quarter of 2018, but it could occur earlier or later based on the rate of events in the study.

Xeloda is a registered trademark of Genentech, Inc.

About Glembatumumab Vedotin

Glembatumumab vedotin is a fully human monoclonal antibody-drug conjugate (ADC) that targets glycoprotein NMB (gpNMB). gpNMB is a protein overexpressed by multiple tumor types, including breast cancer, melanoma, lung cancer, uveal melanoma and osteosarcoma. gpNMB has been shown to be associated with the ability of the cancer cell to invade and metastasize and to correlate with reduced time to progression and survival in breast cancer. The gpNMB-targeting antibody, CR011, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. Glembatumumab vedotin is designed to be stable in the bloodstream but to release MMAE upon internalization into gpNMB-expressing tumor cells, resulting in a targeted cell-killing effect. Glembatumumab vedotin is in development for the treatment of locally advanced or metastatic breast cancer with an initial focus in triple negative disease, stage III and IV melanoma, squamous cell lung cancer and uveal melanoma.

On August 23, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) and Nippon Shinyaku Co., Ltd. (TOKYO: 4516) reported that Chugai filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW), for glycoengineered type II anti-CD20 monoclonal antibody, obinutuzumab (genetical recombination) which was co-developed by the two companies for the treatment of "CD20-positive B-cell follicular lymphoma (FL)" in Japan (Press release, Chugai, AUG 23, 2017, View Source [SID1234520300]).

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"Combination therapy of rituximab and chemotherapy has been used as the standard treatment for CD20-positive B-cell FL for a long time. As a new treatment option, Obinutuzumab was confirmed to be more beneficial than the conventional treatment with rituximab for the treatment of FL," said Dr. Yasushi Ito, Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit. "We are committed to deliver obinutuzumab to patients as early as possible to contribute to the access to better treatments in Japan."

Dr. Kazuya Mori, Nippon Shinyaku’s Corporate Officer, Head of R&D Administration Div. said "I am very glad that a new drug application for our co-developed product, obinutuzumab, was filed. By adding this new product to our lineup in the area of hematologic malignancies, on which we are focusing, we will make utmost efforts to meet the demands of the clinical setting and contribute to the treatment of patients."

This filing was based on the results of the GALLIUM study, a global phase III clinical study conducted by Roche and participating from Japan and other several clinical studies.
The GALLIUM study is a global Phase III open-label, multi-center, randomized two-arm study that evaluated the efficacy and safety of obinutuzumab plus chemotherapy followed by obinutuzumab alone (obinutuzumab arm) compared with rituximab plus chemotherapy followed by rituximab alone (rituximab arm) in 1,401 patients with previously untreated CD20-positive advanced non-Hodgkin’s lymphoma. The primary endpoint of the study was investigator-assessed progression free survival (PFS) in 1,202 patients with FL. The secondary endpoints were PFS assessed by an independent review committee (IRC), overall survival (OS), safety, and other endpoints.

With respect to the primary endpoint, as the median PFS was not reached, the results showed that obinutuzumab arm reduced the risk of disease progression, recurrence or death in patients with FL by 34 percent (HR=0.66, 95% CI: 0.51-0.85, p=0.0012, stratified log-rank test, Data cut-off: January 31, 2016) compared to rituximab arm. Concerning secondary endpoints, the median PFS assessed by the IRC was not reached as well, the risk of disease progression, recurrence or deaths decreased by 29% (HR=0.71, 95% CI: 0.54-0.93], p=0.0138, stratified log-rank test, Data cut-off: January 31, 2016). The median OS did not reach in both arms due to small numbers of events. As for safety, the adverse events (AEs) expressed in both arms in the GALLIUM study were consistent with previous reports. The Grade 3 or higher AEs which was observed in 5% or more frequently for obinutuzumab arm than rituximab arm was neutropenia (43.9% for obinutuzumab arm vs. 37.9% for rituximab arm).

Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells, same as rituximab which is recommended as a treatment of non-Hodgkin’s lymphoma in treatment guidelines in Japan and overseas. Obinutuzumab is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.

In Japan, the prevalence of malignant lymphoma was reported to be approximately 27,000 and the number of deaths due to the disease was reported to be approximately 11,000 in 20121, 2). Since the cases of Hodgkin’s lymphoma is reported to account for approximately 8 to 10% of the cases of malignant lymphoma in Japan3), the prevalence of non-Hodgkin’s lymphoma is estimated to be approximately 24,000 and the number of deaths from this condition is estimated to be approximately 10,000. The prevalence of and deaths from malignant lymphoma tend to increase in recent years1, 2), and a same tendency is seen in patients with non-Hodgkin’s lymphoma.

Chugai and Nippon Shinyaku will work for the early approval to provide obinutuzumab as a new treatment option for patients with CD20-positive B-cell follicular lymphoma and medical professionals.

August 22, 2017 – Curtana Pharmaceuticals, a privately-held, preclinical-stage biopharmaceutical company, reported that it has completed a pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) (Press release, Curtana Pharmaceuticals, AUG 22, 2017, View Source [SID1234520419]). The purpose of the meeting was to discuss the proposed clinical development program for treating newly diagnosed adult glioblastoma (GBM) patients with Curtana’s lead product candidate, CT-179, including the Phase 1 clinical study design. In addition, a clinical development plan for CT-179 in pediatric patients with newly diagnosed high grade glioma (HGG) was proposed.

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Curtana submitted their meeting package to the FDA on May 19, 2017. In written responses, the FDA addressed the company’s questions related to the design of the first-in-human Phase 1 study in adult patients with newly diagnosed GBM. The FDA also provided greater clarity on the data collection requirements in pediatric patients. Last, the Agency provided guidance regarding Curtana’s submission for fast track (FT) designation. Curtana anticipates submitting this IND application in the first half of 2018.

"We are very excited by the FDA’s response and general acceptance of our clinical trial design to study CT-179 in newly diagnosed GBM patients in combination with the standard of care treatments, temozolomide and radiation," said Gregory Stein, M.D., MBA, and Chief Executive Officer. "This is a much-needed departure from the typical development process, which is to first test a new drug as monotherapy in patients with recurrent disease, a strategy that provides safety data, but is frequently unsuccessful in providing adequate evidence of activity. Our goal is to get CT-179 as quickly as possible to adult and pediatric patients with these devastating brain cancers. We applaud the FDA’s acknowledgement of the difficulty treating gliomas and their willingness to be innovative and we will continue to work diligently with the Agency to move our lead product candidate into clinical trials."

Glioblastoma is the most common and most aggressive of the malignant primary brain tumors in adults. According to the American Brain Tumor Association, an estimated 12,390 new cases of GBM are predicted in 2017. Conventional therapeutic approaches for GBM, including surgery, chemotherapy and radiation therapy, target the tumor bulk, but have limited effect on the glioma cancer stem cells (CSCs), which are responsible for the recurrence of disease that occurs in most GBM patients. Accordingly, GBM represents a significant unmet clinical need as the median survival is less than 15 months and five-year survival rate is less than 10%.

Curtana’s lead clinical candidate, CT-179, is a highly potent inhibitor of Olig2, a transcription factor that is not actively expressed in the vast majority of normal adult brain cells or in normal tissues outside the brain. However, Olig2 is markedly over-expressed in GBM; specifically, in the cancer stem cells (CSCs) that have been shown to be an important factor in tumorigenesis, driving tumor growth, invasion into normal brain tissue, and recurrence. The drug is orally bioavailable, readily crosses the blood-brain barrier, achieves very high concentrations in the brain, and significantly prolongs survival in animal models of brain cancer. When combined with standard of care temozolomide and radiation, CT-179 dramatically inhibits tumor growth and prolongs survival compared to either treatment alone, in relevant animal models.

On August 22, 2017 The Alliance Foundation Trials, LLC (AFT), in conjunction with Pfizer and six international cancer research groups, reported the launch of PATINA – a randomized, open-label, Phase 3 clinical study of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor palbociclib (also known as IBRANCE) (Press release, Pfizer, AUG 22, 2017, View Source [SID1234520297]). The PATINA trial will evaluate palbociclib in combination with anti-HER2 therapy and endocrine therapy versus standard therapy as a first-line treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. The trial randomized its first patient on July 26, 2017.

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"The PATINA trial offers an exciting opportunity for a new global collaborative initiative among clinical trial groups aimed at improving the treatment of women with metastatic breast cancer," said Monica M. Bertagnolli, MD, President and Chief Executive Officer of Alliance Foundation Trials, LLC, and group chair and principal investigator of the Alliance for Clinical Trials in Oncology. "Our partnership with the Mastering Breast Cancer Initiative, PrECOG, the German Breast Group, Fondazione Michelangelo, SOLTI Breast Cancer Research Group and the Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) makes this trial available to patients across the U.S., Europe, Australia and New Zealand. PATINA is the first study of the Mastering Breast Cancer Initiative which is an umbrella organization that includes multiple clinical trials whose participants will contribute medical information and biological specimens for future research. This initiative was created in order to understand the natural history of breast cancer and how it evolves over time with the overall goal to develop new treatments for this patient population."

In the U.S., IBRANCE is indicated for the treatment of HR+, HER2-negative (HER2-) advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy. Since its initial FDA approval in 2015, more than 60,000 patients have been treated with IBRANCE in the U.S. alone.

Pre-clinical data and preliminary results from early phase clinical trials point to the potential efficacy of palbociclib when combined with anti-HER2 therapies and endocrine therapy. About 10-15% of patients with metastatic breast cancer are HR+, HER2+.1 Palbociclib is currently not approved for use in this patient population in any country.

"The current PATINA study is built on strong pre-clinical and clinical rationale demonstrating the potential of palbociclib when given in combination with endocrine therapy and anti-HER2 therapies," said Otto Metzger, MD, principal investigator of the trial for AFT and Medical Oncologist at the Dana-Farber Cancer Institute in Boston. "We hope that this trial will show that the addition of palbociclib to the first-line treatment of HR+, HER2+ disease will help delay the onset of therapeutic resistance to endocrine therapy, complement the benefits of anti-HER2 therapy and ultimately improve patient outcomes. The study also includes a comprehensive molecular characterization of the disease when patients enter the study and at the time of disease progression."

"We are pleased to partner with these prominent research groups to explore the use of palbociclib in first-line HR+, HER2+ disease," said Charles Hugh-Jones, MD FRCP, Chief Medical Officer, Pfizer Oncology. "PATINA is the first randomized, Phase 3 trial of a CDK 4/6 inhibitor in this setting. Collaborations of this kind are critical to advance our understanding of how we can treat breast cancer, and they represent an important part of Pfizer’s clinical development program for palbociclib."

The PATINA trial is a pivotal, open-label, international, multicenter, randomized Phase 3 study. The trial is open to women or men with HR+, HER2+ metastatic breast cancer following completion of induction with anti-HER2 based chemotherapy. Participants will be randomized (selected by chance) to one of two treatment arms following 6-8 cycles of chemotherapy with anti-HER2 therapy. One study arm will treat patients with palbociclib (at a dose of 125 mg orally once daily for 21 days followed by seven days off treatment in a 28-day cycle) and standard anti-HER2 therapy and endocrine therapy until disease progression. The other study arm will treat patients with standard anti-HER2 therapy and endocrine therapy until disease progression. About 500 participants will be recruited worldwide.

Alliance Foundation Trials, LLC, under the auspices of the Alliance for Clinical Trials in Oncology, has brought together a collaborative group of breast cancer specialists from around the world to team up with a pharmaceutical sponsor to form a public-private cancer research partnership aimed at bringing more innovative therapies to patients in more efficient ways.

For questions about this trial, please contact the PATINA study at [email protected].

Availability

Currently, the new study is open to physicians and medical facilities throughout the U.S. if they are associated with the Alliance Foundation and PrECOG oncology research groups. The study will be available to non-U.S. sites this fall through an extended academic core network that includes the German Breast Group (GBG), Fondazione Michelangelo, SOLTI Breast Cancer Research Group, and the Australia and New Zealand Breast Cancer Trials Group (ANZBCTG).

Information on the PATINA study can be found on the National Institutes of Health (NIH) registry of clinical trials, www.clinicaltrials.gov (Clinicaltrials.gov Identifier: NCT02947685), and on the PATINA website at www.patina-trial.com.

Funding and Sponsorship

Pfizer, the manufacturer of palbociclib (IBRANCE), is providing funding support for this trial. AFT is the global sponsor of this trial which will be conducted in the U.S., Germany, Italy, Spain, Australia, and New Zealand.