On September 24, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion to expand the indication for Xtandi (enzalutamide) to include adult men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Astellas, SEP 24, 2018, View Source [SID1234529658]).2 If approved by the European Commission (EC), enzalutamide will be one of the first treatments approved for this critical stage of disease, currently associated with a significant unmet medical need. Enzalutamide was first approved by the EC in June 2013 and is currently indicated in the treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT) in whom chemotherapy is not yet clinically indicated or whose disease has progressed on or after docetaxel therapy.3

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"In nmCRPC, the high risk patient is at a stage where his cancer is growing even though it’s not visible yet despite hormone therapy and will manifest itself given time. The objective of early access to enzalutamide in these patients is to delay the emergence of metastasis with the hope of improving quantity and quality of life," said Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, United States, and lead study investigator. "The potential of an effective treatment option for this stage of disease signifies an important therapeutic advancement."

The CHMP opinion is based on the results from the pivotal phase 3 PROSPER trial which evaluated enzalutamide plus ADT vs placebo plus ADT in patients with nmCRPC and rapidly rising prostate-specific antigen (PSA) levels.1 The trial met its primary endpoint of metastasis-free survival (MFS). The median MFS was 36.6 months for men who received enzalutamide plus ADT, compared to 14.7 months with placebo plus ADT (n=1401; HR=0.29 [95% CI: 0.24–0.35]; p<0.001).1

The PROSPER trial results indicated a 71% reduction in the risk of radiographic progression or death in men with nmCRPC and rapidly rising PSA levels, compared to placebo plus ADT (HR=0.29 [95% CI: 0.24–0.35]; p<0.001).1 The most common adverse events of any grade for patients ≥10% and higher for enzalutamide plus ADT vs placebo plus ADT were: fatigue (33% vs 14%), hot flush (13% vs 8%), hypertension (12% vs 5%), nausea (11% vs 9%), fall (11% vs 4%), dizziness (10% vs 4%) and decreased appetite (10% vs 4%).1 These results were published in the June 2018 edition of the New England Journal of Medicine.1

"This positive CHMP opinion represents an important step towards providing specialist health care professionals with a new treatment option for patients with nmCRPC and rapidly rising levels of prostate specific antigen. These patients are at higher risk of developing metastasis and death. Subject to EMA approval, we have the potential to expand the use of enzalutamide in a patient population where there is a clear unmet medical need," said Steven Benner, M.D, Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas.

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for the 28 European Union member countries plus Iceland, Norway and Liechtenstein. The EC, which generally follows the recommendation of the CHMP, is expected to make its final decision in the final quarter of 2018.

PROSPER Trial Results
PROSPER is a double-blind, placebo-controlled, pivotal phase 3 trial conducted at 300 sites in 32 countries that randomised 1,401 patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and a prostate-specific antigen (PSA) doubling time of 10 months or less, 2:1 to either receive once-daily enzalutamide plus androgen deprivation hormone therapy (ADT) (n=933) or placebo plus ADT (ADT alone [n=468]), respectively.1

Secondary outcomes included a statistically significant delay in the median time to first use of new antineoplastic therapy (TTA) of 39.6 vs 17.7 months; HR=0.21 [95% CI: 0.17–0.26]; p<0.001 for patients who received enzalutamide plus ADT compared to those who received placebo plus ADT.1

About Prostate Cancer
Prostate cancer is the most common cancer diagnosis for men in the European Union (EU).4 There are 375,842 men in the EU currently diagnosed with prostate cancer, accounting for an estimated 23.2% of all cancers in men in 2018.4 Some studies estimate that, within five years of diagnosis,10–20% of men with prostate cancer will develop CRPC.5

CRPC refers to the subset of men whose prostate cancer progresses despite castrate levels of testosterone (i.e., less than 50 ng/dL).6 Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising PSA level.6 Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.7,8

About Enzalutamide
Enzalutamide is an oral, once-daily androgen receptor signaling inhibitor. Enzalutamide directly targets the androgen receptors (AR) and exerts its effects on three steps of the AR signaling pathway:3

Inhibits androgen binding: Androgen binding induces a conformational change that triggers activation of the receptor3
Prevents nuclear translocation: Translocation of the AR to the nucleus is an essential step in AR-mediated gene regulation3
Impairs DNA binding: Binding of the AR to the DNA is essential for modulation of gene expression3
Enzalutamide is currently approved in Japan for castration-resistant prostate cancer9 and in July 2018 the United States Food and Drug Administration (FDA) broadened the approved indication for enzalutamide to include men with nmCRPC.10

Important Safety Information for Enzalutamide in the EU
For important Safety Information for enzalutamide please see the full Summary of Product Characteristics at: View Source

About XTANDI (enzalutamide) capsules in the U.S.

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer.

Important Safety Information for XTANDI in the U.S.

Warnings and Precautions
Seizure occurred in 0.4% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. Patients in the study had one or more of the following pre-disposing factors: use of medications that may lower the seizure threshold; history of traumatic brain or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%). Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus 0.5% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures In the placebo-controlled clinical studies, falls occurred in 10% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 8% of patients treated with XTANDI and in 3% of patients treated with placebo. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

Embryo-Fetal Toxicity Safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI. XTANDI should not be handled by females who are or may become pregnant.

Adverse Reactions
The most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the XTANDI patients from the randomized placebo-controlled trials were asthenia/fatigue, decreased appetite, hot flush, arthralgia, dizziness/vertigo, hypertension, headache and weight decreased. In the bicalutamide-controlled study, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In the placebo-controlled study of metastatic CRPC (mCRPC) patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse reactions were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an adverse event as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients. In the bicalutamide-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials in patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In the placebo-controlled trial in patients with nmCRPC, Grade 1-4 neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4) and in 5% of patients receiving placebo (0.2% Grade 3-4).

Hypertension: In the two placebo-controlled trials in patients with mCRPC, hypertension was reported in 11% of XTANDI patients and 4% of placebo patients. Hypertension led to study discontinuation in <1% of patients in each arm. In the placebo-controlled trial in patients with nmCRPC, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo.

Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

On September 24, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the European Commission has granted marketing authorisation for Imfinzi (durvalumab) as monotherapy for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥1% of tumour cells and whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT) (Press release, AstraZeneca, SEP 24, 2018, View Source [SID1234529611]). The approval is based on results from the Phase III PACIFIC trial.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business, said: "Patients in Europe diagnosed with locally-advanced, unresectable non-small cell lung cancer now have a new treatment option. Imfinzi is the only immunotherapy to be approved in this curative-intent setting, and we are proud to bring a new standard of care for this difficult disease."

Dr. Luis Paz-Ares, co-principal investigator of the PACIFIC trial, from the Hospital Universitario Doce de Octubre, Madrid, Spain, said: "Lung cancer is the leading cause of cancer-related death in Europe and approximately a third of European patients with NSCLC present with locally-advanced disease. For decades, the standard of care for these patients has been chemotherapy and radiation therapy followed by active surveillance, after which the majority of patients progress to advanced disease. Imfinzi has demonstrated a compelling survival benefit for these patients in this area of significant unmet need."

The approval follows the positive opinion on 27 July 2018 from the CHMP of the European Medicines Agency.

The most common adverse reactions (greater than or equal to 20% of patients) of Imfinzi versus placebo were cough (40.2% vs. 30.3%), upper respiratory tract infections (26.1% vs 11.5%) and rash (21.7% vs 12.0%). 12.8% of patients experienced a grade 3 or 4 AE with Imfinzi vs 9.8% with placebo.

Imfinzi is approved for the treatment of patients with unresectable, Stage III (locally-advanced) NSCLC in the US, Canada, Switzerland, India, Japan and Brazil. Other global health authority reviews and submissions are ongoing.

About Stage III NSCLC

Stage III (locally-advanced) NSCLC is divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised) to distant organs, as Stage III is currently treated with curative intent.

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries (China, France, Germany, Italy, Japan, Spain, UK, US) in 2017. The majority of Stage III NSCLC patients are diagnosed with unresectable tumours. No new treatments beyond chemoradiation therapy, followed by active surveillance to monitor for progression, have been available to patients for decades.

About PACIFIC

The PACIFIC trial is a Phase III, randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in ‘all-comer’ patients (i.e. regardless of PD-L1 status) with unresectable, Stage III (locally-advanced) NSCLC whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT).

The trial is being conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate, and duration of response.

About Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved for unresectable, Stage III NSCLC in the US, Canada, Switzerland, India, Japan, and Brazil based on the Phase III PACIFIC trial. Imfinzi is also approved for the treatment of patients with locally-advanced or metastatic urothelial carcinoma in the US, Canada, Brazil, Israel, Hong Kong, and India.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with chemotherapy, radiation therapy, small molecules, and tremelimumab, an anti-CTLA4 monoclonal antibody, as a first or second-line treatment for patients with NSCLC, small-cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

On September 24, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that Angelos Stergiou, M.D., ScD h.c., President and Chief Executive Officer of SELLAS, will present a corporate overview at the 2018 Cantor Global Healthcare Conference on Monday, October 1, 2018 at 2:20 p.m. ET at the Intercontinental Barclay Hotel in New York, NY (Press release, Sellas Life Sciences, SEP 24, 2018, View Source [SID1234529564]).

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A live audio webcast of the presentation will be available under "Events & Presentations" in the Investors section of SELLAS’ website at www.sellaslifesciences.com/investors. A replay of the webcast will be available for up to 30 days on SELLAS’ website following the presentation.

On September 24, 2018 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative therapeutics for the treatment of cancer, reported a change in leadership with the appointment of James E. Dentzer as President and Chief Executive Officer effective immediately Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative therapeutics for the treatment of cancer, reported a change in leadership with the appointment of James E. Dentzer as President and Chief Executive Officer effective immediately. In addition, Mr. Dentzer will become a member of the Curis Board of Directors. He replaces Ali Fattaey, Ph.D., who is leaving the Company.

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Mr. Dentzer, who joined Curis in 2016, was promoted earlier this year to Chief Operating Officer to manage all functions outside of research and development, including business development, manufacturing, quality, human resources, finance, legal, IT, and investor and public relations. Mr. Dentzer is also leading the pre-commercial strategic planning for fimepinostat, which received Fast Track designation from the FDA earlier this year for the treatment of patients with Relapsed/Refractory DLBCL.

"The Curis board of directors appreciates the contributions of Dr. Fattaey in transforming Curis into a development-focused company with a pipeline of clinical-stage assets," said Martyn D. Greenacre, the Company’s Chairman. "We wish the best for Ali, who was key in the recruitment of Jim to Curis two years ago. As Chief Operating Officer, Jim has been a driver of the business operations of the Company, while bringing important perspective to the development of Curis’s strategic plan. Looking forward, we believe he is best positioned to lead Curis as we seek to progress our three high-value programs quickly and successfully through the clinic."

Mr. Dentzer brings more than 25 years of experience, including executive leadership roles at Dicerna Pharmaceuticals, Amicus Therapeutics, Valeritas, and Biogen. Mr. Dentzer earned a BA in philosophy from Boston College and MBA from the University of Chicago’s Booth School of Business.

. In addition, Mr. Dentzer will become a member of the Curis Board of Directors. He replaces Ali Fattaey, Ph.D., who is leaving the Company.

Mr. Dentzer, who joined Curis in 2016, was promoted earlier this year to Chief Operating Officer to manage all functions outside of research and development, including business development, manufacturing, quality, human resources, finance, legal, IT, and investor and public relations. Mr. Dentzer is also leading the pre-commercial strategic planning for fimepinostat, which received Fast Track designation from the FDA earlier this year for the treatment of patients with Relapsed/Refractory DLBCL.

"The Curis board of directors appreciates the contributions of Dr. Fattaey in transforming Curis into a development-focused company with a pipeline of clinical-stage assets," said Martyn D. Greenacre, the Company’s Chairman. "We wish the best for Ali, who was key in the recruitment of Jim to Curis two years ago. As Chief Operating Officer, Jim has been a driver of the business operations of the Company, while bringing important perspective to the development of Curis’s strategic plan. Looking forward, we believe he is best positioned to lead Curis as we seek to progress our three high-value programs quickly and successfully through the clinic."

Mr. Dentzer brings more than 25 years of experience, including executive leadership roles at Dicerna Pharmaceuticals, Amicus Therapeutics, Valeritas, and Biogen. Mr. Dentzer earned a BA in philosophy from Boston College and MBA from the University of Chicago’s Booth School of Business.

On September 24, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated results from the ongoing ENCORE 601 cohort enrolling non-small cell lung cancer (NSCLC) patients previously treated with both chemotherapy and PD-(L)1 therapy (Press release, Syndax, SEP 24, 2018, View Source [SID1234529562]). The oral presentation titled, "Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy," was presented by Matthew D. Hellman, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center, at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada. A copy of the presentation is available via the Syndax website at View Source

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"The observation of durable responses seen with the entinostat-pembrolizumab combination in NSCLC patients previously treated with both chemotherapy and PD-(L)1 therapy is an important result, and we look forward to more fully characterizing patient selection tools to identify those who are most likely to respond," said Peter Ordentlich, Ph.D., Syndax co-founder and Chief Scientific Officer. "The exploratory finding that baseline peripheral classical monocytes may predict clinical benefit to the combination provides an opportunity to potentially correlate a readily measurable circulating biomarker with the state of the tumor microenvironment and supports the use of this approach for patient selection in future studies."

The Company previously presented a subset of data from the first 57 patients in the Phase 2 ENCORE 601 NSCLC cohort, which enrolled patients whose disease had progressed after prior chemotherapy and anti-PD-(L)1 treatment, at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting this past June. The updated data set presented today includes data from all 76 patients who enrolled in this cohort prior to the close of enrollment in December 2017, and highlights the durability of the observed responses independent of prior treatment history or PD-(L)1 status. At the time of data cut-off, there were 7 confirmed partial responses (PRs) among the overall population of 72 efficacy-evaluable patients, for a 10% objective response rate (ORR) (95% CI: 4-19%), a median duration of response of 5.3 months, and a median progression free survival (PFS) of 2.8 months. The results did not meet the prespecified ORR endpoint. Six of the 7 responders had low or negative PD-(L)1 expression at study entry. At the time of data cut-off, 6 patients remain on study. Updated data continue to demonstrate a manageable toxicity profile for the entinostat-pembrolizumab combination, with treatment emergent adverse events observed consistent with those previously reported.

Exploratory analysis of baseline biomarkers in the fully enrolled cohort supports the previous observation from the first 57 patients that elevated pre-treatment baseline levels of peripheral classical blood monocytes (CD14+CD16-HLA-DRhi) are associated with enhanced clinical benefit to the entinostat-pembrolizumab combination. Baseline peripheral classical monocyte data were available for 65 of the 72 NSCLC patients evaluable for efficacy and were divided into a group of high baseline monocytes ("monocyte high" n = 19) and low baseline monocytes ("monocyte low" n = 46). The monocyte high subset showed an improved median PFS (5.3 months vs 2.7 months), and an enhanced ORR (21% vs 7%), with 5 of 19 (26%) patients remaining on study compared to only 1 of 46 (2%) in the monocyte low group.

"We continue to remain encouraged by the consistent observation of enhanced clinical benefit in the subgroup of patients who failed prior PD-1 treatment and had high baseline levels of classical peripheral monocytes, a population for whom novel therapies are needed," said Briggs Morrison, M.D., Chief Executive Officer of Syndax. "We recognize the importance of identifying patients more likely to respond to treatment and believe that our updated classical monocyte dataset strengthens the rationale for further validation of this patient selection biomarker. We look forward to communicating our plans for entinostat in this indication in the fourth quarter."

E2112 Update

Syndax also announced today that ECOG-ACRIN Cancer Research Group has informed the Company that enrollment in the ongoing E2112 Phase 3 registration trial of entinostat plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer is now scheduled to close in late October. The Company will release the results of the PFS analysis following its review, and anticipates communicating this in the fourth quarter. The trial remains ongoing, with interim overall survival (OS) analyses scheduled to occur every May and November until either the appropriate number of events are achieved or definitive interim results are obtained.

About Entinostat

Entinostat is a selective, oral, once-weekly inhibitor of class 1 HDACs, currently being evaluated in a pivotal Phase 3 clinical trial (E2112) in combination with exemestane for advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the FDA. Entinostat has also been shown to block the function of immune suppressive cells in the tumor microenvironment, and is being evaluated in combination with several approved PD-1/PD-L1 antagonists, including in ongoing Phase 2 clinical trials combining entinostat with KEYTRUDA from Merck & Co., Inc. for non-small cell lung cancer, melanoma and colorectal cancer (ENCORE 601); with TECENTRIQ from Genentech, Inc. for triple negative breast cancer as well as advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer (ENCORE 602); and with BAVENCIO from Pfizer Inc. and Merck KGaA, Darmstadt, Germany, for ovarian cancer (ENCORE 603).