Epizyme Announces the U.S. Food and Drug Administration Lifts Partial Clinical Hold on Tazemetostat Clinical Program

On September 24, 2018 Epizyme, Inc. (NASDAQ: EPZM), a clinical-stage company developing novel epigenetic therapies, reported the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold that had paused U.S.-based enrollment of new patients in its tazemetostat clinical trials (Press release, Epizyme, SEP 24, 2018, View Source [SID1234529538]). Epizyme is now in the process of reopening enrollment in all of its company-sponsored trials in the U.S., including the follicular lymphoma (FL) EZH2 activating mutation cohort of its Phase 2 non-Hodgkin lymphoma trial.

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Epizyme’s formal response to the FDA included a comprehensive assessment of the risk of secondary malignancies, including T-cell lymphoblastic lymphoma (T-LBL) potentially associated with tazemetostat, which took into account both published literature and the company’s clinical experience to date. This followed a report of a single case of T-LBL in its tazemetostat pediatric study. Epizyme provided a thorough assessment of efficacy and safety data across all of its trials in hematological malignancies and solid tumors, in both adults and children, and convened a panel of external scientific and medical experts who reviewed and validated the findings.

"The Epizyme team has worked diligently to provide a comprehensive response back to the FDA, and through constructive dialogue, we successfully resolved the partial clinical hold. This allows us to turn our full attention to our key priorities: preparing for our first NDA submission for tazemetostat in epithelioid sarcoma and defining our registration path in FL," said Robert Bazemore, president and chief executive officer of Epizyme. "We, along with our investigators and the global experts we consulted to support our complete response, continue to believe in the positive benefit/risk of tazemetostat as we move forward in our clinical development program. We remain steadfast in our commitment to bringing this potential therapeutic option to cancer patients in need of safe and effective new treatments."

Epizyme will now engage with regulators in France and Germany to resolve the partial clinical holds and resume enrollment in those countries. The company is also working closely with its study partners to reach a similar resolution for their respective trials in which tazemetostat is being studied in combination with other therapies.

Investor Conference Call Notice
Company management plans to host a conference call and webcast at 8:30 a.m. EDT today to discuss the resolution of the partial clinical hold. To participate, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 3499753. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast also will be archived on the website for 60 days.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a potent, selective, orally available, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing Phase 2 programs in certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; follicular lymphoma (FL); and combination studies in diffuse large B-cell lymphoma (DLBCL) and non–small cell lung cancer (NSCLC).

Spectrum Pharmaceuticals Announces Release of Updated Poziotinib Data From MD Anderson Phase 2 Study in Non-Small Cell Lung Cancer Patients

On September 24, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported preliminary poziotinib data from the University of Texas, MD Anderson Cancer Center Phase 2 non-small cell lung cancer (NSCLC) study which were released today during an oral presentation at the IASLC 19th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (Press release, Spectrum Pharmaceuticals, SEP 24, 2018, View Source [SID1234529537]). The MD Anderson study is the single largest data set of patients with an exon 20 mutation in EGFR or HER2.

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"There are currently no approved targeted therapies for this hard-to-treat population," said John Heymach, M.D., Ph.D., Chairman and Professor, Department of Thoracic/Head and Neck Medical Oncology, University of Texas, MD Anderson Cancer Center. "For this reason, it is especially exciting to observe that poziotinib is highly active, with a manageable safety profile, in these heavily pre-treated patients. The study is ongoing with nineteen EGFR patients remaining on treatment, six of which have been on drug for longer than a year. Poziotinib may offer a much needed option to NSCLC patients with exon 20 mutations in EGFR or HER2."

In the interim analysis presented at the WCLC, the following observations were made:

This phase II study demonstrates high anti-tumor activity for poziotinib in metastatic, heavily pretreated EGFR exon 20 mutant NSCLC, a group for which no targeted agents have proven effective to date (other than patients bearing T790M or S768I mutations) with best response of PR in 55% of evaluable patients (43% confirmed ORR to date; 19 patients remain on treatment).
Median PFS 5.5m; durable responses observed with 6 treated for >1year thus far.
Compares favorably to historical ORR rates of <8% approved TKIs and <19% for standard of care 2L agents (docetaxel, PD-1/PD-L1 inhibitors).
Significant activity also observed in HER2 exon 20-mutant NSCLC with initial responses observed in 50% (6/12) evaluable patients and median PFS 5.1m.
EGFR-related toxicities (including rash, diarrhea, & paronychia) were manageable and required dose reductions in 60%. Discontinuation due to poor tolerance was rare (3%).
Encouraging activity has prompted a confirmatory, international, multicenter study in EGFR and HER2 exon 20 mutant NSCLC patients which is currently enrolling (NCT03318939), including a first-line cohort, and development of a separate pan-tumor basket study.
The poziotinib NSCLC clinical program for patients with EGFR or HER2 exon 20 insertion mutations currently consists of a Phase 2 investigator-initiated study at The University of Texas, MD Anderson Cancer Center and a Phase 2 pivotal, Spectrum-sponsored, multi-center, global study (ZENITH20) with active sites in the United States and future centers planned in Canada and Europe. The overall poziotinib clinical development program is focused on four pillars, including previously treated NSCLC, first-line treatment of NSCLC, combination therapy and treatment of other solid tumors.

Following the oral presentation of data, Spectrum Pharmaceuticals will be hosting a live webcast featuring Dr. John Heymach.

Conference Call Details:

Monday, September 24, 2018 @ 4:30 p.m. Eastern/1:30 p.m. Pacific

Domestic: (877) 837-3910, Conference ID# 1993267
International: (973) 796-5077, Conference ID# 1993267

The conference call will also be webcast live. To access the webcast and additional documents related to the call, please visit the Investor Relations page of the Spectrum Pharmaceuticals website at View Source

For interested individuals unable to join the call, a replay will be available from September 24, 2018 @ 7:00 p.m. ET/4:00 p.m. PT through October 1, 2018, until 7:30 p.m. ET/4:30 p.m. PT.

Domestic Replay Dial-In: (855) 859-2056, Conference ID# 1993267
International Replay Dial-In: (404) 537-3406, Conference ID# 1993267

About Poziotinib

Poziotinib is a novel, orally available Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.

Genentech’s TECENTRIQ in Combination With Pemetrexed and Platinum-Based Chemotherapy Reduced the Risk of Disease Worsening or Death in a Type of Previously Untreated Advanced Lung Cancer

On September 24, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported results from the Phase III IMpower132 study of TECENTRIQ (atezolizumab) plus pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) for the initial (first-line) treatment of people with non-squamous, non-small cell lung cancer (NSCLC) (Press release, Genentech, SEP 24, 2018, View Source [SID1234529536]). This interim analysis showed that TECENTRIQ and chemotherapy reduced the risk of disease worsening or death (progression-free survival, PFS) by 40 percent compared with chemotherapy alone (PFS=7.6 versus 5.2 months; hazard ratio [HR] = 0.60, 95 percent CI: 0.49-0.72; p<0.0001). While a numerical improvement of 4.5 months for the co-primary endpoint of overall survival (OS) was observed, at this interim analysis statistical significance has not yet been met (median OS=18.1 versus 13.6 months; HR=0.81, 95 percent CI: 0.64-1.03; p=0.0797). The study will continue as planned, with final OS results expected next year. Safety for the TECENTRIQ and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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"This is our third Phase III trial in non-squamous non-small cell lung cancer demonstrating that a TECENTRIQ-based regimen can help reduce the risk of disease progression for people living with this disease," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We will discuss these results with health authorities globally."

Data will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC) on Monday, September 24 at 2:35 – 2:45 p.m. EDT (Abstract OA05.07 Oral) and featured in the official WCLC press conference at 9:45 – 10:30 a.m. EDT.

About the IMpower132 study

IMpower132 is a Phase III, open-label, randomized study evaluating the efficacy and safety of TECENTRIQ plus chemotherapy (cisplatin or carboplatin and pemetrexed) versus chemotherapy alone in chemotherapy-naïve patients with NSCLC. The study enrolled 578 people who were randomized equally (1:1) to receive:

TECENTRIQ in combination with cisplatin or carboplatin and pemetrexed (Arm A), or
Cisplatin or carboplatin and pemetrexed (Arm B, control arm)
During the treatment-induction phase, people received TECENTRIQ, pemetrexed and investigator’s choice of either cisplatin or carboplatin on Day 1 of every three weeks for a dosing period of four or six cycles. People who experienced clinical benefit during the induction phase began maintenance therapy until disease progression.

Safety for the TECENTRIQ and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events (AEs) were reported in 53.6 percent of people receiving TECENTRIQ plus chemotherapy compared to 39.1 percent of people receiving chemotherapy alone.

About lung cancer

According to the American Cancer Society, it is estimated that more than 234,000 Americans will be diagnosed with lung cancer in 2018, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About TECENTRIQ (atezolizumab)

TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the re-activation of T cells. TECENTRIQ may also affect normal cells.

TECENTRIQ U.S. Indication (pronounced ‘tē-SEN-trik’)

TECENTRIQ is a prescription medicine used to treat:

A type of bladder and urinary tract cancer called urothelial carcinoma.

TECENTRIQ may be used when your bladder cancer:
has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, or
you are not able to take chemotherapy that contains any platinum regardless of PD-L1 status on your cancer, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
The approval of TECENTRIQ in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

TECENTRIQ may be used when your lung cancer:
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

It is not known if TECENTRIQ is safe and effective in children.

Important Safety Information

What is the most important information about TECENTRIQ?

TECENTRIQ can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

TECENTRIQ can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucous in the stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with TECENTRIQ if patients have severe side effects.

Before receiving TECENTRIQ, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. TECENTRIQ can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with TECENTRIQ. If patients are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with TECENTRIQ.
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of TECENTRIQ.
are breastfeeding or plan to breastfeed. It is not known if TECENTRIQ passes into the breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TECENTRIQ in people with urothelial carcinoma include:

feeling tired
decreased appetite
nausea
constipation
urinary tract infection
diarrhea
fever
The most common side effects of TECENTRIQ in people with non-small cell lung cancer include:

feeling tired
decreased appetite
muscle pain
cough
shortness of breath
TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

CymaBay Therapeutics to Participate in Upcoming Investor Conferences in October

On September 24, 2018 CymaBay Therapeutics, Inc. (Nasdaq: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that management will participate in upcoming investor conferences, including the 2018 Cantor Global Healthcare Conference, the LEERINK Partners Roundtable Series: Rare Disease & Oncology, and the ROTH Battle of the NASH Thrones Investor Conference (Press release, CymaBay Therapeutics, SEP 24, 2018, View Source [SID1234529535]).

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2018 Cantor Global Healthcare Conference
Date: Monday, October 1
Time: 8:55am Eastern Time
Location: Intercontinental Barclay New York Hotel
Webcast: View Source

LEERINK Partners Roundtable Series: Rare Disease & Oncology
Date: Tuesday, October 2
Time: 8:30am Eastern Time
Location: Lotte New York Palace Hotel
Webcast: View Source

ROTH Battle of the NASH Thrones Investor Conference
Date: Wednesday, October 17
Time: Panel discussions and 1-on-1 meetings
Location: Park Hyatt New York Hotel

ArQule to Present at the Leerink Partners Roundtable Series: Rare Disease & Oncology on October 2, 2018

On September 24, 2018 ArQule, Inc. (Nasdaq:ARQL) reported that Peter Lawrence, President and Chief Operating Officer, Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development, and Marc Schegerin, Senior Vice President, Strategy, Communication and Finance, will present at the Leerink Partners Roundtable Series on October 2, 2018, at 8:00am ET at the Lotte New York Palace in New York City (Press release, ArQule, SEP 24, 2018, View Source [SID1234529534]).

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The live webcast of the presentation will be available via the "Investors & Media" section of ArQule’s website, www.arqule.com, under "Events & Presentations." A replay of the webcast will be available shortly after the conclusion of the presentation.