On June 29, 2017 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for Vectibix (panitumumab) for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC) as first-line therapy in combination with FOLFOX and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy (Press release, Amgen, JUN 29, 2017, View Source [SID1234519732]). Vectibix is the first-and-only fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the FDA for this patient population.

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As part of this new indication, the FDA approved the first multigene, next-generation sequencing-based test to identify the RAS mutation status of a patient’s tumor. Next-generation sequencing is a novel diagnostics test technique that makes a more personalized medicine approach possible. This companion diagnostic helps physicians identify patients that are more likely to benefit from treatment with Vectibix.

"Of the few biomarkers in colorectal cancer, RAS mutation status provides actionable information when deciding on a first-line treatment option in mCRC patients," said Marwan G. Fakih, M.D., co-director of the Gastrointestinal Cancer Program at City of Hope, Duarte, Calif. "Panitumumab has demonstrated a significant overall survival benefit to patients whose mCRC does not have mutations in RAS, providing physicians with a novel targeted treatment option and allowing us to develop a personalized approach as we help patients fight this devastating disease."

The full approval for Vectibix as a treatment for patients with wild-type KRAS mCRC was based on results from the Phase 3 PRIME and ASPECCT trials. The approval of a refined indication for the treatment of patients with wild-type RAS mCRC was based on a retrospective analysis from the PRIME study and prospective, pre-defined analyses from the Phase 3 ‘0007 study. The ‘0007 study evaluated the efficacy of Vectibix plus best supportive care (BSC) versus BSC alone in patients with chemorefractory, wild-type KRAS mCRC. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC treated with Vectibix plus BSC resulted in a statistically significant improvement in overall survival (OS) of 10 months compared to 6.9 months for patients treated with BSC alone (HR=0.70; 95 percent CI: 0.53, 0.93, p=0.0135). The safety profile of Vectibix in patients with wild-type RAS mCRC is consistent with that seen previously in patients with wild-type KRAS mCRC.

"Every patient with cancer is unique, and we are committed to utilizing cutting-edge science and technology to target treatments to the patients more likely to benefit," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This approval for Vectibix reinforces the significance of biomarker testing as a treatment planning tool in metastatic colorectal cancer and further validates the potential for precision medicine to optimize patient outcomes."

Most common adverse reactions (≥ 20 percent) of Vectibix as monotherapy are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. Most common adverse reactions (≥ 20 percent) with Vectibix plus FOLFOX are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus and dry skin. The most common serious adverse reactions (≥ 2 percent difference between treatment arms) were diarrhea and dehydration.

About Colorectal Cancer
Colorectal cancer is the third most common cancer found in both men and women in the U.S., with approximately 135,000 new cases estimated to be diagnosed in 2017.1 Approximately 20 percent of colon cancers are diagnosed at the metastatic stage when the disease has already spread to distant organs, a diagnosis associated with only a 12 percent five-year survival rate.2 Using molecular approaches to identify unique genetic signatures in mCRC has the potential to help improve treatment outcomes.3

About the ‘0007 Study (NCT01412957)
This Phase 3 global, multicenter, randomized, open-label study was designed to evaluate OS with Vectibix and BSC compared to BSC alone in patients with chemorefractory wild-type KRAS (exon 2) mCRC.

The key efficacy analysis of the study showed that Vectibix plus BSC (n=189) was statistically significant to BSC alone (n=188). Patients with wild-type KRAS (exon 2) mCRC treated with Vectibix plus BSC achieved a median OS of 10 months compared to 7.4 months for patients treated with BSC alone (HR=0.73; 95 percent CI: 0.57, 0.93, p=0.0096).

In patients with mutant RAS mCRC, no differences in OS or progression-free survival (PFS) were observed between the treatment arms [OS HR=0.99 (95 percent CI: 0.49, 2.00); PFS HR=1.03 (95 percent CI: 0.56, 1.90)].

No new safety signals were seen in the ‘0007 study. The safety profile was comparable to the known safety profile of Vectibix when administered as a single agent.

About the PRIME Study
PRIME was a randomized, Phase 3, open-label study of Vectibix and FOLFOX combination therapy versus FOLFOX monotherapy in 1,183 adults with untreated mCRC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. The primary endpoints were PFS and OS.

The PRIME study showed that patients with wild-type KRAS tumors (exon 2) achieved statistically significant improvement in PFS with Vectibix and FOLFOX versus FOLFOX alone (9.6 versus 8.0 months [HR=0.80; 95 percent CI: 0.66, 0.97, p=0.02]) and a significant 4.4 month improvement in OS versus FOLFOX alone (23.8 versus 19.4 months [HR=0.82, 95 percent CI: 0.70, 0.98]).

Analyses from the PRIME study evaluated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone in the wild-type RAS subgroup and found that Vectibix plus FOLFOX extended the prespecified major efficacy measure of PFS versus FOLFOX alone, 10.1 months versus 7.9 months, respectively (HR=0.72; 95 percent CI: 0.58, 0.90). The study demonstrated that the median OS for patients treated with Vectibix plus FOLFOX was 25.8 months versus 20.2 months for those treated with FOLFOX alone (HR=0.77; 95 percent CI: 0.64, 0.94). There were no OS or PFS benefit in Vectibix-treated patients with mutant RAS mCRC.

About the ASPECCT Study
ASPECCT was a global, randomized, multicenter, open-label, Phase 3 non-inferiority trial designed to compare the effect of Vectibix versus Erbitux (cetuximab) on OS for monotherapy treatment of 1,010 patients with EGFR-expressing, chemorefractory wild-type KRAS (exon 2) mCRC.

The ASPECCT study met its primary endpoint of non-inferiority for improving OS in patients taking Vectibix (n=499) versus Erbitux (n=100) as a single agent for the treatment of mCRC in patients with wild-type KRAS tumors who have not responded to chemotherapy. Patients treated with Vectibix demonstrated an OS of 10.4 months versus 10 months for patients treated with Erbitux (HR=0.97; 95 percent CI: 0.84-1.11).

About Vectibix (panitumumab)
Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

In June 2017, the FDA approved a refined indication for Vectibix for use in in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.

Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):

As first-line therapy in combination with FOLFOX.
As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
Limitation of Use:
Vectibix is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.

WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 or higher) in 15% of patients receiving Vectibix monotherapy.

In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.

Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix concerning dermatologic toxicity are provided in the product labeling.

Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS."

Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone.

Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.

In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.

Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.

Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.

In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary complications must be carefully considered.

Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix.

Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix for acute or worsening keratitis.

In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).

NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.

Vectibix can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix.

In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.

The most commonly reported adverse reactions (≥ 20%) with Vectibix + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.

To see the Vectibix Prescribing Information, including Boxed Warning visit www.vectibix.com.

On June 29, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported the initiation of the Phase 2 clinical study designed to evaluate the tolerability, safety and efficacy of CRS-207, Aduro’s lead listeria-based immunotherapy construct (LADD), in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the United States and Canada), for the treatment of patients with gastroesophageal adenocarcinoma who have failed two prior chemotherapy treatments (Press release, Aduro Biotech, JUN 29, 2017, View Source [SID1234519730]).

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Clinical trial sites have been activated and the study is open for enrollment. "Gastroesophageal adenocarcinoma is an aggressive, difficult to treat cancer for which there is currently no FDA-approved therapy for those in need of a third-line treatment option," stated Natalie Sacks, M.D., chief medical officer of Aduro Biotech. "We are pleased to be evaluating the CRS-207/KEYTRUDA combination in this Phase 2 clinical trial for late-stage gastroesophageal cancer patients and hope to see similar synergistic anti-cancer activity as observed in preclinical studies with this investigational treatment regimen." The multicenter, single-arm, open-label Phase 2 study is designed to evaluate the safety and efficacy of CRS-207 with KEYTRUDA in adults with gastric, gastroesophageal junction, or esophageal adenocarcinoma who have received two prior systemic chemotherapy treatment regimens for advanced disease. The trial will be conducted at up to 15 sites and will enroll approximately 70 patients. The primary efficacy endpoint is objective response rate, defined as the proportion of patients with either complete or partial responses. For additional information about the study, please visit www.clinicaltrials.gov (search identifier NCT03122548). About Gastroesophageal Adenocarcinoma Gastroesophageal adenocarcinoma is an aggressive form of cancer effecting the esophagus and/or stomach. In 2015, the National Cancer Institute estimated 16,980 new diagnoses of esophageal cancer and 24,590 new diagnoses of gastric cancer will occur in the United States, with an overall five-year survival rate of 20 percent and 30 percent, respectively. Approximately 50 percent of patients present with unresectable or locally advanced disease at the time of diagnosis. Up to approximately 50 percent of these cancer tumor types are known to express mesothelin, a tumor-associated antigen with limited expression on the surface of normal tissues. Currently, there is no U.S. Food and Drug Administration-approved therapy for the third-line treatment of gastroesophageal adenocarcinoma. About LADD and CRS-207 LADD is Aduro’s proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to generate an innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. CRS-207, the company’s lead LADD product candidate, has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including gastric cancer and esophageal adenocarcinoma, as well as mesothelioma, pancreatic, non-small cell lung, ovarian and endometrial cancers.

On June 29, 2017 Celltrion, Inc., a global biopharmaceutical company, and Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for CT-P10, a proposed Monoclonal Antibody (mAb) biosimilar to Rituxan1 (rituximab), which is used to treat patients with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis (Press release, Teva, JUN 29, 2017, View Source [SID1234519725]).

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"As the global leader in biosimilars who brought Inflectra, the world’s first mAb biosimilar approved by the FDA, to the U.S., we are pleased and honored to have this opportunity to once again work with the FDA on CT-P10," said Woo Sung Kee, Chief Executive Officer of Celltrion. "CT-P10, which has been approved in the EU, is continuing to build a solid track record since its launch there earlier this year and has provided patients with access to a high quality treatment option and has offered great savings in healthcare costs. I am hopeful that CT-P10 will bring similar benefits to the U.S. when approved."

The BLA for CT-P10 includes data for CT-P10 and reference rituximab in terms of efficacy, safety, immunogenicity, pharmacodynamics (PD) and pharmacokinetics (PK). These trials were conducted in over 600 patients and include up to 104 weeks of data. CT-P10 was approved by the European Commission in February 20172 and has launched in the U.K., Germany, Netherlands, Spain and the Republic of Korea.

"Teva is pleased to announce this important milestone today, with our partner Celltrion, bringing us one step closer to making additional biosimilar treatment options available to patients in the U.S.," said Paul Rittman, Senior Vice President and General Manager, Teva Oncology. "We look forward to leveraging Teva’s unique cross-functional capabilities across both specialty and generic medicines to continue our commitment to serving those dealing with cancer, rheumatoid arthritis, and other serious diseases."

Celltrion and Teva entered into an exclusive partnership to commercialize CT-P10 and CT-P6, a biosimilar to Herceptin (trastuzumab), in the U.S. and Canada in October 2016. As part of the agreement, Teva is responsible for all commercial activities in the U.S. and Canada, pending regulatory approvals for both products. Celltrion has responsibility for completing all clinical development and regulatory activities.

The BLA for CT-P10 has been accepted for filing by the FDA for standard review, with FDA Regulatory Action expected during the first quarter of 2018.

On June 29 2017 Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento"), reported today that the U.S. Food and Drug Administration (FDA) has authorized the Company’s Investigational New Drug Application (IND) for Resiniferatoxin (RTX), a non-opioid, TRPV1 agonist that selectively targets afferent nerve activation involved in chronic pain states (Press release, Sorrento Therapeutics, JUN 29, 2017, View Source [SID1234519722]). Sorrento intends to promptly initiate a multicenter, Phase 1b clinical trial of RTX administered by epidural injection for the treatment of intractable pain associated with cancer. RTX has been granted FDA Orphan Drug Status for pain associated with end stage disease.

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"Given its unique mechanism of action, we view RTX as a franchise molecule, uniquely positioned to halt the neurogenic inflammation cycle in a number of clinical indications. Our intention is to commence our clinical path in cancer since more than 80% of cancer patients experience uncontrolled pain during their disease and 20% of these patients remain unresponsive or intolerant to mainstay, opioid therapy[i]. We are confident in RTX providing meaningful relief to these patients given previous pre-clinical and clinical findings demonstrating that a single injection of RTX could safely and effectively reduce severe pain as well as the use of concomitant analgesics. " said Dr. Henry Ji, President and Chief Executive Officer of Sorrento Therapeutics, Inc.

RTX has been extensively tested in animals and is currently the subject of a Phase I clinical trial at the National Institute of Health (NIH) under a Cooperative Research and Development Agreement (CRADA). To date, 12 patients with terminal cancer pain have been treated. When injected intrathecally, RTX has been shown to directly interact with nerve cells expressing TRPV1 receptors without affecting normal sensation (touch and vibration sense) or muscle function. Preliminary results from the NIH trial demonstrate that a single injection of RTX was well tolerated at the dose levels tested and provided clinically meaningful reductions in pain and a reduced dependence on opioids. In contrast to opioids, RTX treatment did not result in systemic adverse events such as cognitive impairment, sedation or respiratory depression, and enabled patients to increase their activity levels.

On June 29, 2017 Novartis reported the European Commission approved expanding the use of Zykadia (ceritinib) to include the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive (Press release, Novartis, JUN 29, 2017, View Source [SID1234519721]). Approval follows a positive opinion granted in May by the Committee for Medicinal Products for Human Use (CHMP), and is applicable to all 28 European Union member states plus Iceland, Lichtenstein, and Norway.

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The first-line approval of Zykadia is based on results from an open-label, randomized, multicenter, global, Phase III trial, ASCEND-4. The study met its primary endpoint, demonstrating a 45% reduction in the risk of disease progression in the Zykadia arm, compared to the chemotherapy arm (hazard ratio [HR] = 0.55 [95% confidence interval (CI): 0.42, 0.73; one-sided p value <0.0001])[1]. Patients treated with first-line Zykadia had a median progression-free survival (PFS) of 16.6 months (95% CI: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance[1].

Overall intracranial response rate (OIRR) in patients with measurable brain metastases at baseline and at least one post-baseline assessment was 72.7% (95% CI: 49.8, 89.3; n = 22) for patients treated with Zykadia, versus 27.3% (95% CI: 10.7, 50.2; n = 22) for patients treated with chemotherapy[1]. The whole body overall response rate (ORR) was 72.5% (95% CI: 65.5, 78.7; n = 189) in patients treated with Zykadia[1].

Further, patients without brain metastases at screening receiving Zykadia experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69])[1]. Among patients with brain metastases at screening, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group, versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12])[1].

"Today’s EC approval of Zykadia as a first-line treatment of ALK+ non-small cell lung cancer is an important step forward for patients with this type of serious disease," said Bruno Strigini, CEO, Novartis Oncology. "Our commitment to innovation in lung cancer will continue and we look forward to providing additional advancements for patients as the incidence of the disease grows around the world."

In May, US Food and Drug Administration (FDA) approved the expanded use of Zykadia to include the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test.

Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year[3],[4].

Over the past decade, Novartis Oncology’s research has supported the evolution of treatment approaches for patients living with mutation-driven types of lung cancer. The company continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genomic biomarkers in NSCLC.

About ASCEND-4
ASCEND-4 is a Phase III randomized, open-label, multicenter, global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK-positive advanced NSCLC who received no prior therapy for their advanced disease. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed-based platinum doublet chemotherapy (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) for four cycles followed by pemetrexed maintenance.

Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and 187 (62 with brain metastases) to chemotherapy[1]. Approximately 59.5% of patients with measurable brain metastases at baseline did not have prior radiation therapy, the current standard of treatment for baseline brain metastases[1]. One hundred and five (105) patients out of the 145 patients (72.4%) that discontinued treatment in the chemotherapy arm received subsequent ALK inhibitor as first antineoplastic therapy. Of these patients 81 received Zykadia[1].

The most common adverse reactions in ASCEND-4 (incidence >=25% all grades) were diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), decreased appetite (34%) and cough (25%). Grade 3/4 adverse reactions (incidence >=2%) were fatigue (7%), vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss (3.7%), nausea (2.6%) and prolonged QT interval (2.6%). The most common laboratory abnormalities in ASCEND-4 (incidence >=25% all grades) were increased ALT/AST (91%/86%), increased GGT (84%), increased alkaline phosphatase (81%), creatinine increase (77%), anemia (67%), hyperglycemia (53%), decreased phosphate (38%), increased amylase (37%) and neutropenia (27%). Grade 3/4 laboratory abnormalities (incidence >=2%) were increased GGT (49%), ALT/AST (34%/21%), increased alkaline phosphatase (12%), hyperglycemia (10%), increased amylase (8%), increase lipase (6%), creatinine increase (4.2%), anemia (4.2%), decreased phosphate (3.7%) and neutropenia (2.1%).

About Zykadia
Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia is currently approved in over 70 countries worldwide. Please visit View Source for additional information.

Zykadia Important Safety Information
Zykadia may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting and stomach-area pain. These problems can be severe. Zykadia may also cause severe liver injury, abnormal heartbeats (slow, fast, or irregular), severe or life-threatening swelling (inflammation) of the lungs that can lead to death, pancreatitis, and high levels of pancreatic enzymes or glucose (sugar) in blood.

Zykadia may harm unborn babies. Women who are able to become pregnant must use a highly effective method of birth control (contraception) during treatment with Zykadia and up to 3 months after stopping Zykadia. Patients and their healthcare provider should decide whether to take Zykadia or breastfeed, but should not do both.

Some side effects can be serious and patients should call your healthcare provider immediately if experiencing changes in your heartbeat (fast, slow, or irregular), lightheadedness, fainting, dizziness, pain in the chest, cough, difficult or painful breathing, wheezing, pain in chest when inhaling, fever, yellow skin and eyes, nausea, loss of appetite, dark urine, and severe upper stomach pain.

Before taking Zykadia, patients should tell their healthcare provider about all medical conditions, including liver problems, diabetes or high blood sugar, heart problems, including a condition called long QT syndrome, if they are pregnant, if they think they may be pregnant, or if they plan to become pregnant, are breastfeeding or plan to breastfeed. Patients should also tell their healthcare provider about all medicines they take. Patients should not drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it may make the amount of Zykadia in their blood increase to a harmful level.

Patients should have blood tests before starting treatment with Zykadia to check their liver, pancreas, and the level of sugar in blood. While taking Zykadia, blood tests to check the liver should be performed monthly, while pancreas and the level of sugar in blood should be performed regularly.

The most common adverse reactions with an incidence of >=10% diarrhea, nausea, vomiting, liver laboratory test abnormalities, fatigue, abdominal pain, decreased appetite, weight decreased, constipation, blood creatinine increased, rash, anemia, and esophageal disorder. Grade 3-4 adverse reactions with an incidence of >=5% were liver laboratory test abnormalities, fatigue, vomiting, hyperglycemia, nausea, diarrhea.

Please see full Prescribing Information for Zykadia.