On June 1, 2018 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported the National Institute for Health and Care Excellence (NICE) will make ZEJULA (niraparib), the first PARP inhibitor shown to be effective in patients with a BRCA mutation as well as those without a BRCA mutation, available to women in England and Wales with recurrent platinum-sensitive ovarian cancer via the Cancer Drugs Fund (CDF)1 (Press release, TESARO, JUN 1, 2018, View Source [SID1234527048]). NICE has recommended ZEJULA via the CDF for women with a BRCA mutation who have received two lines of chemotherapy and in women without a BRCA mutation who have received two or more lines of chemotherapy.

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"At TESARO, we continue to globalize our mission and bring transformative therapies to patients. We are pleased that NICE will now provide more women with recurrent ovarian cancer in England and Wales access to ZEJULA through the CDF," said Orlando Oliveira, Senior Vice President and General Manager, TESARO International. "Through close partnership with both NICE and NHS, TESARO can now offer ZEJULA as an option for second-line maintenance treatment, regardless of a patient’s BRCA status."

The CDF is a source of funding for cancer drugs in England, providing patients access to promising new oncology treatments while NHS England and NICE analyze any additionally requested data to inform a final reimbursement decision on a new treatment or indication. Overall survival data for ZEJULA are not yet available, and as a result NICE has recommended ZEJULA for use within the CDF while further data are collected2. Interim funding is provided via the CDF, giving patients access to the treatment through a managed access arrangement.

"Recurrent ovarian cancer is an aggressive form of cancer where a key goal of treatment is to keep women in remission and off chemotherapy for as long as possible – allowing them the best chance for a good quality of life," said Jonathan Ledermann, Professor of Medical Oncology at the University College London Cancer Institute. "ZEJULA offers the chance to delay this cancer from returning or progressing for months, and possibly years in some cases. It is a significant step forward. Crucially, this decision opens the door for many women who, until now, have not had the option of maintenance treatment with a PARP inhibitor."

About Ovarian Cancer
In the UK, ovarian cancer has the highest mortality rate of all gynecological cancers3. It has one of the highest incidence rates in Europe4 with survival rates among the lowest5. The rate of newly diagnosed cases of ovarian cancer in the UK is 16 per 100,000 of the population compared to the European average of 12.6 per 100,0005. Every year 4,100 women lose their lives to ovarian cancer – 11 women every day6.

The most common symptoms of ovarian cancer include abdominal or pelvic pain, bloating, difficulty eating, and urinary urgency, all of which are commonly associated with less serious conditions. 60% of women with ovarian cancer are diagnosed in an advanced stage7, when prognosis is poor. Although significant progress has been made in treatment of ovarian cancer, the disease recurs in approximately 85% of women with advanced ovarian cancer8, at which point it may be incurable9,10. Recurrent ovarian cancer is the sixth most common cause of cancer death among women and has the highest mortality rate of all gynecological cancers.

About ZEJULA (niraparib)
Niraparib is marketed in the United States and Europe under trade name ZEJULA. ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated 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. 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.

ZEJULA is approved in Europe as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response (CR) or partial response (PR) to platinum-based chemotherapy. The approval was based on data from the clinically rigorous ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. ZEJULA is the first once-daily, oral poly (ADP-ribose) polymerase (PARP)1/2 inhibitor to be approved in Europe that does not require BRCA mutation or other biomarker testing.

The primary endpoint of the trial was progression free survival (PFS). Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by a robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with or without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (hazard ration (HR) 0.27) 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 approved starting dose of ZEJULA is 300 milligrams once per day. According to the European summary of product characteristics (SmPC), in patients below 58 kilograms, a starting dose of 200 milligrams once per day may be considered. The most commonly administered dose of ZEJULA over the course of the Phase 3 NOVA clinical trial was 200 milligrams once per day, following dose modification. Further exploratory analyses of the NOVA study indicated that individual dose modification maintained efficacy and reduced the rate of new adverse events.11

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some 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.

On June 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported the first data from the ongoing Phase 1 study evaluating single agent AG-881 in advanced glioma and other solid tumors (Press release, Agios Pharmaceuticals, JUN 1, 2018, View Source [SID1234527032]). The data were featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. AG-881 is an investigational, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes, which was designed for enhanced brain penetrance for development in IDH-mutant glioma.

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"IDH mutant glioma is a distinct disease where patients are typically diagnosed in their thirties and forties and endure a deteriorating quality of life from the side effects associated with multiple rounds of surgery, radiation and chemotherapy and ultimately die of their disease," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "The AG-881 Phase 1 dose-escalation data are encouraging, as they demonstrate a favorable safety profile at lower dose levels and show signals of clinical activity that support further evaluation of the role of inhibiting mutant IDH in low-grade glioma."

"With no curative or approved targeted therapies for low-grade glioma and a poor long-term prognosis, we are committed to exploring the novel mechanism of action of our IDH inhibitors in this indication," said Chris Bowden, M.D., chief medical officer at Agios. "Data from our ivosidenib and AG-881 Phase 1 trials and the ongoing perioperative study, combined with feedback from regulators and the neurology community, will inform our pivotal development plan."

The ongoing Phase 1 dose-escalation trial is assessing the safety and tolerability of AG-881 in IDH1/2 mutant advanced solid tumors, including glioma. As of the March 29, 2018 data cut-off, 93 patients (52 with glioma and 41 with other solid tumors) have been treated with single agent AG-881. Enrollment is complete and 17 glioma patients and 1 non-glioma solid tumor patient remain on treatment. Study design, status and baseline characteristics for the 52 glioma patients are reported below.

Forty-eight percent of patients (n=25) had World Health Organization (WHO) classified Grade 2 tumors, 42% (n=22) had Grade 3 tumors, 8% (n=4) had Grade 4 tumors and 2% (n=1) was unknown.
Ninety-two percent of patients (n=48) had an IDH1 mutation and 6% (n=3) had an IDH2 mutation. One patient did not have a biopsy but was confirmed as IDH mutant positive due to 2-HG elevation by magnetic resonance spectroscopy (MRS).
The median age of these patients is 42.5 years (ranging from 16-73 years).
Patients received a median of two prior systemic therapies (ranging from one to six).
— Seventy-three percent of patients (n=38) had previously received temozolomide and 58% percent (n=30) had previously received radiotherapy.
Patients received daily doses of AG-881 ranging from 10 mg to 300 mg.
The median treatment duration was seven months (ranging from 0-27 months) for all glioma patients, 12 months (ranging from 1-27 months) for non-enhancing glioma and 3 months (ranging from 0- 27 months) for patients with enhancing disease.
Safety Data

The safety analysis conducted for all 93 treated patients as of the data cut-off demonstrated that AG-881 has a favorable safety profile at dose levels below 100 mg.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>33%) being fatigue, nausea, increases in alanine aminotransferase (ALT) and increases in aspartate aminotransferase (AST).
Grade 3 or higher AEs were observed in 33% of all patients (n=31).
Dose limiting toxicities (DLTs) of Grade 2 or higher elevated transaminases occurred in five glioma patients at the higher dose levels (≥100 mg) and resolved to Grade ≤1 with dose modification or discontinuation. There were no treatment-related on-treatment deaths.
A maximum tolerated dose (MTD) was not reached by Bayesian model; the doses chosen for further clinical development were based on safety, pharmacokinetics and pharmacodynamics data.

Efficacy Data

Efficacy data from the 52 glioma patients (23 with non-enhancing and 29 with enhancing disease) as of the data cut-off showed:

One patient with non-enhancing disease and a 1p19q co-deletion had a sustained minor response according to the investigator by Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG) and remains on treatment.
Seventy-five percent of patients (n=39) had a best response of stable disease, including 20 patients with non-enhancing disease.
Thirty-five percent of patients (n=18, including 13 patients with non-enhancing disease) remained on treatment for ≥1 year.
Efficacy data from the 41 patients with non-glioma solid tumors as of the data cut-off showed:

One patient with cholangiocarcinoma had a partial response, 37% of patients (n=15) had stable disease and 44% (n=18) had progressive disease.
The median treatment duration was 2 months (ranging from 0-18 months).
Ongoing Perioperative Study in Glioma
A perioperative ‘window’ trial with ivosidenib and AG-881 (10 mg and 50 mg) in up to 45 IDH1m non-enhancing low-grade glioma patients is ongoing. The goal of the trial is to confirm CNS penetrance and tumor 2-HG suppression of ivosidenib and AG-881 as part of the strategy to finalize pivotal development plans by year-end 2018.

About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor with a five-year survival rate of 33 percent. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH1 mutation.

On June 1, 2018 Amgen (NASDAQ:AMGN) reported results from the Phase 3 A.R.R.O.W. trial of a once-weekly KYPROLIS (carfilzomib) dosing regimen in patients with relapsed and refractory multiple myeloma (Press release, Amgen, JUN 1, 2018, View Source;p=RssLanding&cat=news&id=2352822 [SID1234527033]). In the trial, KYPROLIS administered once-weekly at 70 mg/m2 with dexamethasone (once-weekly Kd) achieved superior progression-free survival (PFS) and overall response rates (ORR), with a comparable safety profile, versus twice-weekly KYPROLIS at 27 mg/m2 and dexamethasone (twice-weekly Kd). These data were presented during an oral session at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and simultaneously published in The Lancet Oncology.

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"Proteasome inhibitors, like KYPROLIS, are essential in treating patients with multiple myeloma and have helped improve patient outcomes," said Maria-Victoria Mateos, M.D., Ph.D., director of the myeloma unit, University Hospital of Salamanca-IBSAL in Salamanca, Spain. "The A.R.R.O.W. trial showed that when given once per week at the higher dose of 70 mg/m2 with dexamethasone, KYPROLIS achieved superior progression-free survival and overall response rates, with a comparable safety profile, versus the twice-weekly regimen."

The KYPROLIS clinical program continues to focus on providing solutions for physicians and patients in treating this frequently relapsing and difficult-to-treat cancer. A.R.R.O.W. is the first and only randomized Phase 3 head-to-head trial to compare two different dosing schedules of KYPROLIS.

"Through our patient-centric approach, we strive to improve outcomes and experience for patients with multiple myeloma," said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "Results from A.R.R.O.W. show patients can benefit from receiving KYPROLIS with a once-weekly dosing schedule. We have engaged with regulatory agencies and look forward to filing as soon as possible to potentially expand our label to include this option for patients with relapsed and refractory multiple myeloma."

A.R.R.O.W. included 478 patients with relapsed and refractory multiple myeloma who received two or three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent (IMiD). Patients in the trial treated with once-weekly Kd achieved a statistically significant 3.6 month improvement in PFS compared to the twice-weekly regimen (median PFS 11.2 months for once-weekly Kd versus 7.6 months for twice-weekly Kd; HR=0.69; 95 percent CI: 0.54-0.88; one-sided p=0.0014).The ORR in patients treated with once-weekly Kd was 62.9 percent versus 40.8 percent for those treated with the twice-weekly regimen (p<0.0001). In addition, 7.1 percent had complete responses or better in the once-weekly arm versus 1.7 percent in the twice-weekly arm in this refractory patient population.

The overall safety profiles of the two arms were comparable, with no new safety risks identified in the once-weekly arm. The most frequently reported treatment-emergent adverse events (greater than or equal to 20 percent) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia and pyrexia.

About A.R.R.O.W.
The A.R.R.O.W. (RAndomized, Open-label, Phase 3 Study in Subjects with Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination with Dexamethasone, Comparing Once-Weekly versus Twice-weekly Carfilzomib Dosing) trial evaluated 478 patients with relapsed and refractory multiple myeloma who have received at least two but no more than three prior therapies, including bortezomib and an immunomodulatory drug. Those included in the study were randomized to receive a 30-minute infusion of once-weekly KYPROLIS (20 mg/m2 on day 1 of cycle 1; 70 mg/m2 on days 8 and 15 of cycle 1; and 70 mg/m2 on days 1, 8 and 15 of subsequent cycles) with dexamethasone (40 mg) versus a 10-minute infusion of twice-weekly KYPROLIS (20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 on days 8, 9, 15 and 16 of cycle 1; and 27 mg/m2 on days 1, 2, 8, 9, 15 and 16 of subsequent cycles) with dexamethasone (40 mg). The primary endpoint of the trial was PFS, defined as the time from randomization to disease progression or death. Secondary endpoints included ORR, overall survival, and safety and tolerability. The trial was conducted in approximately 100 sites worldwide. For more information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT02412878.

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 life-threatening disease that accounts for approximately one percent of all cancers.2,3 Worldwide, approximately 114,000 people are diagnosed with multiple myeloma each year and 80,000 patient deaths are reported on an annual basis.2

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 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.4,5

Since its first approval in 2012, approximately 80,000 patients worldwide have received KYPROLIS. 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 United States. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

Important U.S. KYPROLIS (carfilzomib) 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 control and fluid management) prior to starting treatment with KYPROLIS and remain under close follow‐up.
Acute Renal Failure

Cases of acute renal failure, including some fatal renal failure events, 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. It is recommended to control hypertension prior to starting KYPROLIS. 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

On June 1, 2018 SELLAS Life Sciences Group Inc., (Nasdaq:SLS) (SELLAS) reported that the sponsor-principal investigator, after taking into account that key clinical development objectives were met as well as other regulatory considerations, and in agreement with SELLAS, determined to terminate early the Phase 2b independent investigator-sponsored clinical trial (IST) of trastuzumab (Herceptin) +/- nelipepimut-S (NeuVax) in HER2 1+/2+ breast cancer patients (Press release, Sellas Life Sciences, JUN 1, 2018, View Source [SID1234527360]). In this Phase 2b study, Herceptin was provided under a Clinical Trial Supply Agreement by Genentech, Inc. The decision to early terminate this Phase 2b study was based in part on the previously announced recommendation of the independent Data Safety Monitoring Board (DSMB) to further advance the development of the NeuVax + Herceptin combination for the triple negative breast cancer (TNBC) patient population. Data from the Phase 2b has been submitted for presentation at a major medical conference that will take place during the second half of 2018.

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"We wish to thank our patients and their families for their participation in this trial. Based on data demonstrating that this combination therapy has the potential to become an important therapeutic option for TNBC patients facing a life-threatening disease and for whom current options in the adjuvant setting are extremely limited, we have determined, in consensus with SELLAS, to close out the current study," stated COL (ret) George E. Peoples, MD, FACS, Founder and Director of Cancer Insight, LLC and study Principal Investigator. "We look forward to supporting SELLAS’ interactions and discussions with regulatory bodies."

SELLAS conducted this week two advisory meetings with global experts in regulatory affairs and breast cancer clinical development in order to determine the optimal path for further development of the NeuVax + Herceptin combination in TNBC in a pivotal setting and engagement with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

As previously announced, a pre-specified interim analysis of safety and efficacy conducted by the DSMB, demonstrated a clinically meaningful and statistically significant difference between the TNBC cohort of patients and the control arm with a hazard ratio of 0.26, p-value = 0.023, in favor of the NeuVax + Herceptin combination compared to Herceptin alone. The analysis also showed an adverse event profile with no notable differences between treatment arms and no additional cardiotoxicity in the NeuVax + Herceptin arm. Based on these positive results, the DSMB recommended to expeditiously seek regulatory guidance from the FDA for further development of the combination of NeuVax + Herceptin in TNBC, a population with a large unmet medical need.

"We agree with Dr. Peoples’ decision to close this Phase 2b study earlier than planned and it is a priority to advance the development program for NeuVax + Herceptin in TNBC. Indeed, we have initiated the necessary steps for prompt engagement with the regulatory authorities for their guidance on the expeditious development of this combination therapy, as exemplified by the clinical and regulatory advisory board meetings we just conducted during this year’s ASCO (Free ASCO Whitepaper) meeting," said Nicholas J. Sarlis, MD, PhD, FACP, Executive Vice President and Chief Medical Officer of SELLAS.

Providing their impressions from the discussion of the Phase 2b study data during the Clinical Advisory Board meeting at the ASCO (Free ASCO Whitepaper) conference, Debu Tripathy, MD, Professor and Chairman, Department of Breast Medical Oncology, The University of Texas – MD Anderson Cancer Center, mentioned that "in early stage TNBC the benefit of chemotherapy in the adjuvant setting is incomplete and leaves room for improvement. Further, to date, targeted therapies have not proven effective for TNBC. Targeting HER2 as an immune therapy target with the Herceptin plus NeuVax combination in HER2 1+/2+ TNBC makes sense biologically, especially considering the baseline presence of activated cellular immunity components in most patients with this tumor type," while Prof. Dr. med. Volkmar Müller, MD, PhD, Professor and Deputy Director, Department of Gynecology, University Clinic of Hamburg-Eppendorf, Germany commented, "The data from the Phase 2b study of Herceptin + NeuVax are promising in the TNBC cohort. SELLAS’ decision to pursue clinical and regulatory strategies with this combination in TNBC based on the current findings is justified, due to the high unmet need, low number of competing trials in the maintenance/adjuvant setting and feasibility of a pivotal Phase 3 study design whereby a relapse-based endpoint could be reached with confidence." Neither Prof. Tripathy nor Prof. Dr. med. Müller participated in the NeuVax + Herceptin Phase 2b study.

SELLAS also announced that it has appointed Jeffrey S. Weber, MD, PhD, as Chairman of its SAB. In his new role, together with the other members of the Company’s SAB, Dr. Weber will strengthen the Company’s capacities to drive, position and prioritize pipeline development with key focus on two assets, galinpepimut-S and nelipepimut-S (NeuVaxTM).

"We are very proud to expand Jeff’s role on the Company’s SAB. Jeff is a leading expert in cancer immunotherapeutics, with broad advisory experience to biopharmaceutical companies in the immuno-oncology field and has a proven leadership track in academic centers. His insights and ability to coordinate and collaborate with our SAB members and our scientific and clinical leadership will help us to more efficiently develop our peptide immunotherapeutic vaccines candidates," said Dr. Sarlis. "Having worked with Jeff as a member of our SAB over the past 2 years, we are delighted to strengthen our collaboration," added Dr. Sarlis.

Dr. Weber currently serves as Co-Director of the Melanoma Program at the New York University (NYU)-Langone Perlmutter Cancer Center and Deputy Director of the Center. Prior to this position, he was Head of the Melanoma Center of Excellence at H. Lee Moffitt Cancer Center. Earlier in his career, Dr. Weber worked as a Senior Investigator in the Surgery Branch of the National Cancer Institute (NCI) at the National Institutes of Health (NIH) and before that served as Chief of Medical Oncology at the University of Southern California (USC)’s Keck School of Medicine. He is a member of the Editorial Boards at Journal of the National Cancer Institute, Clinical Cancer Research, Human Gene Therapy and Journal of Immunotherapy and has served on or chaired numerous NCI study sections. Dr. Weber has published more than 180 articles in the top peer-reviewed journals, including New England Journal of Medicine and Nature Medicine. Dr. Weber was the recipient of the Bob Chandler Courage Award from the USC, of a K24 Mid-Career Mentor Award from NIH, has been recognized as one of the "Best Doctors in America" for over a decade and was the OncLive Giants of Cancer in Melanoma for 2016. He was also the first investigator to demonstrate that PD-1 inhibitors had encouraging activity in resected melanoma patients.

"I am delighted to become the Chairman of the Scientific Advisory Board of SELLAS and honored to work together with my colleagues at the SAB to meaningfully support the company’s quest to change the field by innovative approaches to vaccinate patients using immunogenic peptides for the treatment of cancer," commented Dr. Weber.

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

On June 1, 2018 Cambrex Corporation (NYSE: CBM), a leading manufacturer of small molecule innovator and generic Active Pharmaceutical Ingredients (APIs), reported that Steven Klosk, President and Chief Executive Officer, will present at the Jefferies 2018 Global Healthcare Conference on June 7, 2018 at 9:30 a.m. EDT in New York City (Press release, Cambrex, JUN 1, 2018, View Source [SID1234527035]).

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The live audio webcast and slide presentation can be accessed from the Cambrex website at www.cambrex.com in the Investors section under "Webcasts & Presentations", and a replay will be available for 90 days after the live event concludes