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Aduro Biotech Announces Initiation of Phase 2 Clinical Trial of CRS-207 in Combination with KEYTRUDA® (pembrolizumab) for the Treatment of Previously-Treated Gastroesophageal Adenocarcinoma

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.

Celltrion and Teva Announce U.S. FDA Acceptance of Biologics License Application for Proposed Biosimilar to Rituxan® (rituximab)

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]).

"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.

Sorrento Therapeutics Announced FDA Authorization of IND to Commence Clinical Trial of RTX in Intractable Cancer Pain

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.

"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.

Novartis receives EU approval for first-line use of Zykadia® in ALK-positive advanced non-small cell lung cancer (NSCLC)

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.

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.

CytomX Achieves Development Milestone in Strategic Oncology Collaboration with AbbVie for CD71-Targeting Probody Drug Conjugate

On June 29, 2017 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported that the company has advanced CX-2029, a Probody drug conjugate (PDC) targeting CD71 and being developed in collaboration with AbbVie, into GLP toxicology studies, a key step on the path to filing an Investigational New Drug (IND) application in 2018 (Press release, CytomX Therapeutics, JUN 29, 2017, View Source [SID1234519720]). Upon commencement of the GLP toxicology study, CytomX will receive a $15 million milestone payment from AbbVie as part of the 2016 strategic oncology collaboration between the companies.

"CD71 is highly attractive for delivery of cytotoxic payloads to cancer cells, but its presence on normal cells has precluded the development of antibody drug conjugates using this high-potential target. We have used our Probody platform to design and optimize CX-2029, a CD71-targeting Probody drug conjugate with the potential to safely and effectively treat a wide range of cancers," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "Rapid progression of the CX-2029 program to this important milestone has been enabled by our close collaboration with AbbVie, and we look forward to advancing this first-in-class molecule into the clinic."

About CD71 and the CytomX/AbbVie 2016 Strategic Oncology Collaboration
CytomX and AbbVie are co-developing a PDC against CD71, with CytomX leading pre-clinical and early clinical development. CD71 is also known as the transferrin receptor 1 (TfR1), the biological function of which is to internalize iron-complexed transferrin into dividing cells. CD71 is highly and homogeneously expressed on many solid and hematologic tumor types. These properties render CD71 an ideal target for antibody drug conjugate strategies except for the fact that the target is present on most normal cells. CX-2029 has been designed to target CD71 on tumor cells and spare normal cells by localizing the drug candidate’s activity primarily to cancer tissue. AbbVie will lead later development and commercialization with global late-stage development costs shared between the two companies. CytomX received an upfront payment of $30 million and is eligible to receive up to $470 million in development, regulatory and commercial milestones, pending the achievement of pre-determined outcomes. AbbVie will lead global commercial activities with CytomX eligible to receive a profit share in the U.S. and tiered double-digit royalties on net product sales outside of the U.S. CytomX retains an option to co-promote in the U.S.

AbbVie also receives exclusive worldwide rights to develop and commercialize Probody drug conjugates against up to two additional, undisclosed targets. Should AbbVie ultimately pursue these targets, CytomX is eligible to receive additional milestone and royalty payments per target on any resulting products.