CEL-SCI REPORTS MONTHLY PATIENT ENROLLMENT IN JANUARY FOR ITS PHASE 3 HEAD AND NECK CANCER TRIAL

On February 1, 2016 CEL-SCI Corporation (NYSE MKT: CVM) ("CEL SCI" or the "Company") reported that during the month of January it has enrolled 29 patients in its ongoing Phase 3 trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary head and neck cancer (Press release, Cel-Sci, FEB 1, 2016, View Source [SID:1234508929]). Total patient enrollment for the trial is now 697 as of January 31, 2016 in the world’s largest Phase 3 study in head and neck cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Enrollment this month was impacted by the Christmas and Orthodox Christmas holidays. We expect enrollment to increase again in the coming months," stated CEL-SCI CEO Geert Kersten.

The current study goal is to enroll 880 patients through approximately 100 clinical centers in over 20 countries.

About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling patients with advanced primary squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that is given BEFORE surgery, radiation and chemotherapy because that is when the immune system is thought to be the strongest, one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, and at University of California, San Francisco (UCSF), as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. Dr. Joel Palefsky, a world-renowned scientist and Key Opinion Leader (KOL) in human papilloma virus (HPV) research and the prevention of anal cancer, is the Principal Investigator at UCSF, which was added to the study in July 2015.

CEL-SCI has also entered into two additional co-development agreements for up to $3 million each with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

MabVax Therapeutics Receives FDA Authorization for Phase I Clinical Trial with 89Zr-HuMab-5B1 as PET Imaging Agent for Pancreatic Cancer

On February 1, 2016 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage oncology drug-development company, reported receipt of notice from the U.S. Food and Drug Administration (FDA) authorizing initiation of a Phase I clinical trial with 89Zr-HuMab-5B1 as a new generation PET scan cancer imaging agent in patients with pancreatic cancer (Press release, MabVax, FEB 1, 2016, View Source [SID:1234508927]). The Company filed an Investigational New Drug (IND) application for this trial with the FDA on December 29, 2015. MabVax previously announced receipt of FDA authorization for a Phase I trial with HuMab-5B1 as a therapeutic treatment for patients with pancreatic cancer, and patient enrollment in both Phase I trials is expected to commence in the first quarter of 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase I clinical trial with 89Zr-HuMab-5B1 is designed to enroll up to 28 patients previously diagnosed with pancreatic cancer, who will be administered 89Zr-HuMab-5B1. Patients will return for additional visits on days 2, 4 and 7 for imaging and safety assessments. The trial will evaluate the safety, pharmacokinetics and biodistribution of 89Zr-HuMab-5B1, as well as determine the ideal dose and conditions for an optimal PET scan image. MabVax expects to report the initial set of images from this trial by mid-year 2016 and anticipates that patient enrollment will be completed before the end of 2016.

The 89Zr-HuMab-5B1 imaging agent is MabVax’s HuMab-5B1 fully human antibody conjugated to a radioactive label. It is being developed to take advantage of the antibody’s ability to target pancreatic cancer cells and attach to pancreatic tumors to improve their detection. 89Zr-HuMab-5B1 has demonstrated high-resolution images of tumors in xenograft animal models and results of advanced preclinical study were published in the peer-reviewed Journal of Nuclear Medicine on September 12, 2013. Additionally, MabVax has received $1.75 million from the National Institutes of Health (NIH) for the development of 89Zr-HuMab-5B1 as an imaging agent for pancreatic cancer. 89Zr-HuMab-5B1 also has the potential as a companion diagnostic for MabVax’s HuMab-5B1 therapeutic product.

"Our HuMab-5B1 products represent a novel approach to harnessing the immune system to diagnose and treat cancer, and we are delighted with the FDA’s expeditious response to our IND filings," said David Hansen, MabVax’s President and Chief Executive Officer. "We expect to report interim data from both Phase I trials by the middle of this year, which could have a positive impact on our future commercial and corporate development activities. We also plan to pursue additional programs with HuMab-5B1 as well as follow-on antibodies under development at MabVax that have the potential for dual-product applications for additional types of cancer."

About HuMab-5B1

MabVax’s antibody is fully human and was discovered from the immune response of cancer patients vaccinated with an antigen-specific vaccine during a Phase I trial at Memorial Sloan Kettering Cancer Center. In preclinical research, the HuMab-5B1 antibody has demonstrated high specificity and affinity, and has shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancers. The antigen the antibody targets is expressed on more than 90% of pancreatic cancers making the antibody potentially broadly applicable to most patients suffering from this type of cancer.

Bristol-Myers Squibb Foundation Awards Eight Grants Totaling Nearly $11.5M to Make Lung and Skin Cancer Screening, Care More Accessible in High-Risk U.S. Communities

On February 1, 2016, Bristol-Myers Squibb Foundation reported eight grants totaling nearly $11.5 million that will help make lung and skin cancer screening programs, care and patient support more accessible to underserved populations (Press release, Bristol-Myers Squibb, FEB 1, 2016, View Source [SID:1234508926]). The goal is to develop, validate and sustain models that deliver equitable and optimal outcomes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The grants were awarded through the Foundation’s Bridging Cancer Care and Specialty Care for Vulnerable Populations initiatives. Bridging Cancer Care focuses on pilot projects in select southeastern U.S. states with the highest lung cancer burden to advance evidence-based strategies to improve lung cancer screening and assist patients diagnosed with lung cancer access and navigate cancer care and community-based supportive services. Specialty Care for Vulnerable Populations supports care collaborations among primary care and specialty care providers and patient engagement and social support in order to improve the quality of specialty care services for underserved populations living with lung cancer, skin cancer or HIV.

Lung cancer is the leading cause of cancer death in the U.S., with a mortality rate higher than any other cancer, primarily because the cancer is not detected or treated at an early stage.

"Obstacles to screening, especially for minority and underserved populations, often result in patients receiving a late-stage diagnosis, which dramatically reduces their chances for survival," says John Damonti, president, Bristol-Myers Squibb Foundation. "We are pleased to engage our partners to develop innovative programs that will improve the health outcomes of underserved patient populations facing lung cancer, to help prevent skin cancer among migrant worker populations and to advocate for system-wide change to remove barriers to specialty care."

The Association of Community Cancer Centers (ACCC) received a three-year, $4.1 million grant to develop a collaborative approach to improving lung cancer care for Medicaid patients. ACCC will develop and validate an Optimal Care Coordination Model and engage ACCC’s member cancer programs and practices which includes more than 20,000 multidisciplinary providers, community health centers, patient advocacy organizations, health system leadership, payers and policymakers, to strengthen and complete lung cancer systems of care and improve outcomes for Medicaid patients.

"Lung cancer is the deadliest cancer facing our nation today, and tackling this disease requires a fully integrated approach that treats the full patient," says Steven L. D’Amato, BSPharm, BCOP, president, ACCC. "With this collaboration, ACCC looks forward to bringing our unmatched expertise in multidisciplinary cancer care to improve cancer coordination across the country so that vulnerable populations living with lung cancer have access to the treatment they need."

Anne Arundel Medical Center received a three-year, $1.25 million grant to replicate and expand the medical center’s successful Rapid Access Chest and Lung Assessment Program, which reduced the time from lung cancer screening to diagnosis from as much as four months for outpatients to an average of 16 days by quickly identifying, engaging and managing patients through an increased centralization of care and a thoracic nurse navigator. The program will focus on low-income and racial minority patients who are at risk for or diagnosed with lung cancer in Maryland’s Anne Arundel, Calvert and Prince George counties.

"While Anne Arundel Medical Center’s DeCesaris Cancer Institute’s lung screening and thoracic oncology programs have continued to expand over the past five years, our successes have been more limited among vulnerable, lower-income and minority populations," says Stephen Cattaneo, MD, medical director of Thoracic Oncology at Anne Arundel Medical Center. "The grant from the Bristol-Myers Squibb Foundation will allow us the opportunity to better reach and inform these at-risk patients in our area and surrounding Maryland counties about the need for lung cancer screening while providing desperately needed education and resources for smoking cessation."

The American Cancer Society received a three-year, $1.25 million grant to partner with three federally qualified heath centers (FQHCs) – Valley Health in Huntington, West Virginia; Christ Community Health Services in Memphis, Tennessee; and a third to be identified – to introduce patient education and clinic-based navigation services to support patients from lung cancer screening through diagnosis.

Screening for lung cancer in high-risk current or former smokers is one of the most important emerging cancer control opportunities. The FQHCs will work with primary and specialty care providers to ensure they are prepared to assess patient risk for lung cancer, support a shared decision about screening and provide referrals for those with a positive screening result.

"Implementing lung cancer screening demands an integrated system involving primary care, radiology, pulmonary physicians, screening facilities, as well as a cancer treatment team," says Richard Wender, MD, chief cancer control officer for the Society. "This new grant will allow Society staff to work with the FQHCs to learn how to build capacity to provide high-quality lung cancer screening for low-income communities."

The Patient Advocate Foundation received a three-year, $1.36 million grant for a program linking West Virginia’s lung cancer patients to case management support, which responds to a decision for the Centers for Medicaid and Medicare Services to provide coverage for annual low-dose CT lung cancer screening for at-risk patients. The project will identify barriers to care for vulnerable populations and develop strategies to link patients to providers, increase community awareness of lung cancer screening and make available the Lung Cancer CareLine, a system that provides hands-on comprehensive navigation of the health care system to increase access to emerging therapies and treatment.

The Ralph Lauren Center for Cancer Care and Prevention (RLC), in partnership with Memorial Sloan Kettering Cancer Center, received a two-year, $604,582 grant to pilot a lung cancer screening and continuum of care access program for patients in underserved and high-risk populations in the Harlem and northern Manhattan sections of New York City.

RLC will use new approaches, including community outreach and patient incentives, to encourage more people to get screened for lung cancer. Outreach workers and care navigators from RLC will partner with community-based organizations, houses of worship and primary health care centers to educate people about the importance of lung cancer screening and navigate them through care. Memorial Sloan Kettering will also help to identify high-risk patients through smoking cessation programs as well as assist with access to treatment and care.

"The Ralph Lauren Center for Cancer Care and Prevention has a strong history of pioneering new models, including a groundbreaking patient navigation program in East Harlem," says Gina Villani, MD, MPH, chief executive officer, RLC. "The patients we serve face numerous obstacles to medical screening and care, and often feel disenfranchised by the medical community. Our community-based and community-focused approach will engage those patients to be screened and, if needed, treated for lung cancer."

Farmworker Justice received a two-year, $750,000 grant to engage a diverse range of stakeholders to develop a demonstration project in California and Florida to promote community integration of skin cancer services and reduce the impact of skin cancer among farmworkers and their families. Although farmworkers in the U.S. are exposed to living and working conditions that double their risk of developing melanoma and other skin cancers, access to skin cancer prevention, screening and specialty care and services are difficult to obtain.

"In addition to providing access to skin cancer detection services, resulting in earlier detection of skin cancer and appropriate skin cancer treatment, this project will develop and share effective approaches and strategies to address the particular needs and wishes of farmworker communities and increase the ability to inform and influence national private and public sector decision-makers to better respond to this important public health issue," says Bruce Goldstein, president, Farmworker Justice.

In addition, two program support grants totaling nearly $2 million were awarded to FSG and The Center for Health Law and Policy Innovation at Harvard Law School to help translate successful models emerging from Specialty Care for Vulnerable Populations and Bridging Cancer Care into sustainable cancer and specialty care services through alternative funding, payment reform and institutional and public policy change.

Nektar Publishes Pre-clinical Results for NKTR-214, an Investigational CD122-Biased Immune-Stimulatory Cytokine for the Treatment of Cancer in Clinical Cancer Research

On February 1, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported the publication in Clinical Cancer Research of pre-clinical findings for NKTR-214 (Press release, Nektar Therapeutics, FEB 1, 2016, View Source [SID:1234508925]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The paper, titled "NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models," (Charych et al., Clin Cancer Res, doi:10.1158/1078-0432.CCR-15-1631) documents a broad set of pre-clinical data supporting the clinical advancement of NKTR-214. Among the findings reported, treatment with NKTR-214 led to durable and specific anti-tumor immunity in multiple syngeneic mouse models both as a single agent and as combination therapy with checkpoint inhibitors. In addition, treatment with single-agent NKTR-214 in tumor-bearing mice resulted in a controlled, sustained, and biased T-cell activation leading to a 450:1 mean ratio of CD8-positive effector T cells to T-regulatory cells in the tumor microenvironment, while maintaining more balanced ratios in non-tumor tissues and circulation.

"NKTR-214 allows us to capture and harness the power of the IL-2 biological pathway, which is known to promote T cell growth, to stimulate the body’s own immune system to target and fight cancer. The design of NKTR-214 gives it a combination of biophysical, biochemical, and pharmacological properties that translate into a desirable anti-tumor immune profile," said Stephen Doberstein, Ph.D., Senior Vice President and Chief Scientific Officer of Nektar Therapeutics.

The newly published data documented in the paper also support the favorable safety profile of NKTR-214. The compound was well-tolerated in rodents and in non-human primates (NHPs). Importantly, these pre-clinical safety studies showed that NKTR-214 did not lead to hypotension or vascular leak syndrome at predicted clinical therapeutic doses.

As documented in the new publication, in a pre-clinical tumor re-challenge study in an EMT6 mouse breast cancer model, dosing of NKTR-214 in combination with anti-CTLA-4 antibody resulted in durable and complete responses lasting up to 170 days (5.5 months). When tumor-free animals were re-challenged with the same tumors with no additional treatment, the complete responders demonstrated sustained vaccine-like resistance. These results suggest that NKTR-214 provides a complementary mechanism of immune activation when used concurrently with approved antibody therapies.

"We are pleased that the unique mechanism, efficacy and safety of NKTR-214 are now described and published in a prestigious peer-reviewed journal that is widely read by oncologists, scientists and physician-scientists," said Dr. Doberstein. "We are continuing to advance NKTR-214 in an ongoing Phase 1/2 clinical trial in cancer patients and we expect to have preliminary top-line results from the first stage of this study in the second half of 2016."

About the NKTR-214 Phase 1/2 Clinical Study

NKTR-214 is currently being evaluated in a Phase 1/2 clinical study in patients with advanced solid tumors, including melanoma, renal cell carcinoma and non-small cell lung cancer. The ongoing study is being conducted at MD Anderson Cancer Center and Yale Cancer Center and is comprised of two stages. The first stage is an open-label, multi-dose, dose-escalation study evaluating single-agent NKTR-214 treatment in approximately 20 patients with solid tumors. The primary objective of the first stage of the study is to evaluate the safety and efficacy of NKTR-214, and to define the recommended Phase 2 dose. In addition, the study will assess preliminary anti-tumor activity, including objective response rate (ORR). The immunologic effect of NKTR-214 on tumor-infiltrating lymphocytes (TILs) and other immune cells in both blood and tumor tissue will also be assessed. Following the dose-escalation stage of the study, dose expansion cohorts are planned to evaluate NKTR-214 in specific tumor types, including melanoma, renal cell carcinoma and non-small cell lung cancer.

For more information on the ongoing NKTR-214 Study, please visit the "Clinical Trials" section of www.mdanderson.org using identifier 2015-0573 or visit View Source

About NKTR-214

NKTR-214 is a CD122-biased immune-stimulatory cytokine, which is designed to stimulate the patient’s own immune system to kill tumor cells. By biasing activation to the CD122 receptor, NKTR-214 enhances CD8+ effector T cells (tumor-killing cells) in the tumor. In pre-clinical studies, a single dose of NKTR-214 resulted in a 400-fold AUC exposure within the tumor compared with an equivalent dose of the existing IL-2 therapy, enabling, for the first time, an antibody-like dosing regimen for a cytokine.

Exelixis Announces Positive Overall Survival Results from METEOR, the Phase 3 Pivotal Trial of Cabozantinib in Advanced Renal Cell Carcinoma

On February 1, 2016 Exelixis, Inc. (NASDAQ:EXEL) reported positive overall survival (OS) results from METEOR, the phase 3 pivotal trial comparing cabozantinib to everolimus in 658 patients with advanced renal cell carcinoma (RCC) who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor (TKI) (Press release, Exelixis, FEB 1, 2016, View Source [SID:1234508924]). In a second interim analysis for OS, a secondary endpoint of the trial, the results showed a highly statistically significant and clinically meaningful increase in OS for patients randomized to cabozantinib as compared to everolimus. Ongoing study monitoring did not identify any new safety signals. Exelixis intends to present these data at a medical meeting later this year.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With these results, cabozantinib is now the first and only therapy evaluated in a large, pivotal study in previously treated patients with advanced renal cell carcinoma to demonstrate a benefit in all three key efficacy parameters – overall survival, progression-free survival and objective response rate," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "This is an important moment for the kidney cancer community, including the patients, clinical investigators, and Exelixis team members who made the METEOR trial possible. Exelixis will share these new results with regulators as part of ongoing review processes in the United States and European Union. Our highest priority is to bring this new option for advanced RCC to patients as quickly as possible."

In late December 2015, Exelixis announced that it completed the submission of its rolling New Drug Application (NDA) for cabozantinib as a treatment for patients with advanced RCC who have received one prior therapy; the U.S. Food and Drug Administration (FDA) recently granted Priority Review to the application and set a Prescription Drug User Fee Act action date of June 22, 2016. The FDA previously granted Breakthrough Therapy and Fast Track designations to cabozantinib for its potential advanced RCC indication.

On January 28, 2016, the European Medicines Agency (EMA) validated Exelixis’ Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced renal cell carcinoma who have received one prior therapy. The MAA has been granted accelerated assessment, making it eligible for a 150-day review, versus the standard 210 days (excluding clock stops when information is requested by the EMA’s Committee for Medicinal Products for Human Use).

Both regulatory applications are based on the results of METEOR. In July 2015, Exelixis announced top-line results from METEOR demonstrating that the trial had met its primary endpoint of improving progression-free survival; compared with everolimus, a standard of care therapy for second line RCC, cabozantinib was associated with a 42% reduction in the rate of disease progression or death. Median PFS for cabozantinib was 7.4 months as compared to 3.8 months with everolimus (HR=0.58, 95% CI 0.45-0.75, p < 0.001). Cabozantinib also significantly improved the objective response rate as compared to everolimus. These data were later presented at the European Cancer Congress in September 2015 and concurrently published in The New England Journal of Medicine.

Cabozantinib is currently marketed in capsule form under the brand name COMETRIQ in the United States for the treatment of progressive, metastatic medullary thyroid cancer (MTC), and in the European Union for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. COMETRIQ is not indicated for patients with RCC. In the METEOR trial, and all other cancer trials currently underway, Exelixis is investigating a tablet formulation of cabozantinib distinct from the COMETRIQ capsule form. The tablet formulation of cabozantinib is the subject of the NDA and MAA for advanced RCC.

About the METEOR Phase 3 Pivotal Trial

METEOR is an open-label, event-driven trial with the primary endpoint of progression-free survival (PFS). The target enrollment for METEOR was 650 patients, and 658 patients were ultimately randomized. The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia. Patients were randomized 1:1 to receive 60 mg of cabozantinib daily or 10 mg of everolimus daily, and were stratified based on the number of prior VEGF receptor TKI therapies received, and on commonly applied RCC risk criteria developed by Motzer et al. No cross-over was allowed between the study arms.

Secondary endpoints for METEOR include OS and objective response rate. The secondary endpoint of OS assumed a median of 15 months for the everolimus arm and 20 months for the cabozantinib arm. The study was designed to observe 408 deaths in the entire intent-to-treat population of 650 planned patients, providing 80% power to detect a HR of 0.75. An interim analysis of OS at the 2-sided 0.0019 level employing a Lan-DeMets O’Brien-Fleming alpha-spending function was planned at the time of the primary analysis for PFS, if the trial met the primary PFS endpoint. This analysis showed a strong trend in OS favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005), although the p-value of 0.0019 to achieve statistical significance was not reached at that time. Based upon these results and after consulting with the FDA and EMA, a second interim analysis was undertaken; the results of this second interim analysis crossed the boundary for early declaration of statistical significance.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2015 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; however, the five-year survival rate for patients with advanced or late-stage metastatic RCC is under 10 percent, with no identified cure for the disease.3

Until the introduction of targeted therapies into the RCC setting a decade ago, treatments for metastatic RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon). In the second and later-line settings, which encompass approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two small-molecule therapies and an immune checkpoint inhibitor have been approved for the treatment of patients with advanced RCC who have received prior systemic therapy. The currently approved small-molecule agents have shown little differentiation in terms of efficacy and have demonstrated only modest progression-free survival benefit in patients refractory to sunitinib, a commonly-used first-line therapy.

The majority of clear cell RCC tumors exhibit down-regulation of von Hippel-Lindau protein function, either due to gene inactivation or epigenetic silencing, resulting in a stabilization of the hypoxia-inducible transcription factors and consequent up-regulation of VEGF, MET and AXL.5 The up-regulation of VEGF may contribute to the angiogenic nature of clear cell RCC, and expression of MET or AXL may be associated with tumor cell viability, a more invasive tumor phenotype and reduced overall survival. 6 Up-regulation of MET and AXL in clear cell RCC has also been shown to occur in response to treatment with VEGF receptor TKIs in preclinical models, indicating a potential role for MET and AXL in the development of resistance to these therapies.7

About Cabozantinib

Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGF receptors, AXL and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and maintenance of the tumor microenvironment.

Cabozantinib, marketed under the brand name COMETRIQ, is currently approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC).

The European Commission granted COMETRIQ conditional approval for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.

Important Safety Information, including Boxed WARNINGS

WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE

Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.

Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.

COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.

Wound complications have been reported with COMETRIQ.

COMETRIQ treatment results in an increase in hypertension.

Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients treated with COMETRIQ.

The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.

Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.

Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.

COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.

COMETRIQ can cause fetal harm when administered to a pregnant woman.

Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

Please see full U.S. prescribing information, including Boxed WARNINGS, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf

Please refer to the full European Summary of Product Characteristics for full European Union prescribing information, including contraindication, special warnings and precautions for use at www.sobi.com once posted