On September 1, 2016 Array BioPharma (Nasdaq: ARRY) reported that the FDA has accepted its New Drug Application (NDA) for binimetinib with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017 (Press release, Array BioPharma, SEP 1, 2016, View Source [SID:1234514864]). Array completed its NDA submission of binimetinib in late June 2016 based on findings from the pivotal Phase 3 NEMO (NRAS MELANOMA AND MEK INHIBITOR) trial in patients with NRAS-mutant melanoma. The FDA also indicated that it plans to hold an advisory committee meeting (ODAC) as part of the review process. As previously reported, Array is currently preparing for an Application Orientation Meeting (AOM) with the FDA in September 2016, which it expects will include a discussion of the NDA package including clinical risk / benefit.

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"There are very few treatment advances beyond immunotherapy for this devastating disease, which impacts one out of five advanced melanoma patients," said Victor Sandor, M.D., Chief Medical Officer, Array BioPharma. "Binimetinib is the first and only MEK inhibitor to demonstrate improvement on progression free survival in a Phase 3 trial for NRAS mutant melanoma patients."

About the Phase 3 NEMO Study

The NEMO trial, (NCT01763164), is an international, randomized Phase 3 study evaluating the safety and efficacy of 45 mg BID binimetinib, compared to 1,000 mg/m2 dacarbazine dosed every three weeks. Prior immunotherapy treatment was allowed, and patients underwent radiographic assessment of disease status every six weeks. Assessment of progression was determined by blinded central review. Over 100 sites across North America, Europe, South America, Asia and Australia participated in the study.

Results from the NEMO trial were presented at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting. The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. The median PFS on the binimetinib arm was 2.8 months, versus 1.5 months on the dacarbazine arm. In the pre-specified subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab or pembrolizumab, patients who received binimetinib experienced 5.5 months of median PFS, compared with 1.6 months for those receiving treatment with dacarbazine. While the results in the pre-specified sub-group of patients who had received prior treatment with immunotherapy are of interest, interpretation beyond overall consistency with the primary result should be made with care. Array anticipates that the primary consideration for marketing approval will be the results for the primary endpoint of the trial. In addition to improving PFS, binimetinib also demonstrated improvement in overall response rate (ORR) and disease control rate. While there was no statistically significant difference demonstrated in overall survival (OS), the median overall survival (mOS) favored the binimetinib arm. Under the NEMO protocol, and in accordance with accepted statistical practice, the subgroup analyses of OS are formally conducted only if the key secondary endpoint of OS reached statistical significance. Binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS-mutant melanoma patients.

Binimetinib is an investigational medicine and is not currently approved in any country.

About NRAS-Mutant Melanoma
Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with more than 76,000 new cases and nearly 10,000 deaths from the disease projected in 2016. Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and is a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and patients face poor clinical outcomes and high mortality.

About Binimetinib
MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor, which targets key enzymes in this pathway.

Binimetinib is currently being studied in several other oncology trials, including the Phase 3 COLUMBUS trial studying encorafenib in combination with binimetinib in patients with BRAF-mutant melanoma and the recently initiated BEACON trial that will study encorafenib in combination with binimetinib and cetuximab in patients with BRAF V600E-mutant colorectal cancer. Array projects COLUMBUS top-line results availability during the third quarter of 2016.

On September 1, 2016 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results for TECENTRIQ from the Phase III study, OAK (Press release, Genentech, SEP 1, 2016, View Source [SID:1234514850]). The study met its co-primary endpoints and showed a statistically significant and clinically meaningful improvement in overall survival (OS) compared with docetaxel chemotherapy in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease progressed on or after treatment with platinum-based chemotherapy. Adverse events were consistent with what has been previously observed for TECENTRIQ. Genentech looks forward to presenting full results at an upcoming medical meeting in 2016.

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"These results add to the growing body of evidence that supports the role of TECENTRIQ as a potential new treatment for specific types of advanced NSCLC," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "This is very encouraging news for people living with this disease because lung cancer is the leading cause of cancer deaths around the world. We hope to bring this treatment option to patients as soon as possible."

The FDA granted Breakthrough Therapy Designation (BTD) for TECENTRIQ for the treatment of people with PD-L1 (programmed death-ligand 1) positive NSCLC whose disease has progressed during or after platinum-based chemotherapy (and appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumor). Genentech’s Biologics License Application (BLA) for NSCLC was granted Priority Review with an action date of Oct. 19, 2016.

Genentech has eight Phase III lung studies underway evaluating TECENTRIQ alone or in combination with other treatments in people with early and advanced stages of lung cancer.

About the OAK study

OAK is a Phase III, global, multicenter, open-label, randomized, controlled study evaluating the efficacy and safety of TECENTRIQ compared with docetaxel in people with locally advanced or metastatic NSCLC whose disease progressed on or after treatment with platinum-containing chemotherapy.

The study’s co-primary endpoints were overall survival in:
All people randomized to treatment in the study (intention-to-treat or ITT population), and
a PD-L1 selected subgroup of people
PD-L1 expression was assessed on both tumor cells (TC) and tumor-infiltrating cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics, and was defined as people whose tumors were determined to express PD-L1 with an IHC score of TC1/2/3 or IC1/2/3.
Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), duration of response (DOR) and safety.
A total of 1,225 patients were enrolled and randomized 1:1 to receive either docetaxel (75 mg/m2 intravenous infusion) or TECENTRIQ (1200 mg intravenous infusion) every three weeks. Treatment on TECENTRIQ continued as long as patients experienced clinical benefit as assessed by the investigator or until unacceptable toxicity. The primary efficacy analysis was based on the first 850 randomized patients, and the secondary efficacy analysis will include all 1,225 randomized patients.

About non-small cell lung cancer

According to the American Cancer Society, it is estimated that more than 224,000 Americans will be diagnosed with lung cancer in 2016, 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 activation of T cells. TECENTRIQ may also affect normal cells.

TECENTRIQ is the first and only anti-PD-L1 cancer immunotherapy approved by the FDA, and is indicated for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). This indication for TECENTRIQ is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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

TECENTRIQ is a prescription medicine used to treat:

A type of bladder cancer called urothelial carcinoma. TECENTRIQ may be used when bladder cancer has spread or cannot be removed by surgery (advanced urothelial carcinoma) and,
The patient has tried chemotherapy that contains platinum, 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

Important Information About TECENTRIQ

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

Getting medical treatment right away may help keep these problems from becoming more serious. The healthcare provider may treat the patient with corticosteroid or hormone replacement medicines. The healthcare provider may delay or completely stop treatment with TECENTRIQ if severe side effects occur.

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 of pneumonitis may include: new or worsening cough, shortness of breath, or 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, 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 in the stools or dark, tarry, sticky stools, severe stomach area (abdomen) pain or tenderness
Hormone Gland Problems (especially the pituitary, thyroid, adrenal glands and pancreas) – 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, voice gets deeper, urinating more often than usual, nausea or vomiting, stomach area (abdomen) pain
Nervous System Problems (neuropathy, meningoencephalitis) – Signs of nervous system problems may include: severe muscle weakness, numbness or tingling in hands and feet, fever, confusion, changes in mood or behavior, extreme sensitivity to light, neck stiffness
Inflammation of the Eyes – Symptoms may include blurry vision, double vision, other vision problems, eye pain or redness
Severe Infections – Symptoms of infection may include: fever, cough, frequent urination, flu-like symptoms, pain when urinating
Severe Infusion Reactions – Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling like passing out, back or neck pain, facial swelling
The most common side effects of TECENTRIQ include:

feeling tired
decreased appetite
nausea
urinary tract infection
fever
constipation
These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information.

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.
If patients are able to become pregnant, they should use an effective method of birth control during 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 of the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the TECENTRIQ full Prescribing Information for additional Important Safety Information.