Combination EGFR + TNF Inhibition May Knock Out Most Lung Cancers

MedicalResearch.com Interview with:

Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center

Dr. Amyn Habib

Amyn Habib, M.D.
Associate Professor, Neurology & Neurotherapeutics
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study?

Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  Continue reading

Combination Axitinib + Pembrolizumab Active Against Renal Cell Carcinoma

MedicalResearch.com Interview with:

Prof. Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center William M. Scholl Professor and Vice-Chair Department of Oncology and  Professor of Medicine Georgetown University Medical Cente

Prof. Atkins

Prof. Michael B. Atkins, MD
Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center
William M. Scholl Professor and Vice-Chair Department of Oncology and
Professor of Medicine
Georgetown University Medical Center 

MedicalResearch.com: What is the background for this study?

Response: Prior studies combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF)-pathway have been characterized by excess toxicity precluding further development. We hypothesized that axitinib, a more selective VEGF inhibitor would combine safely with pembrolizumab (anti-PD-1) and yield antitumour activity in treatment-naïve patients with advanced renal cell carcinoma.

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Melanoma: New Combination Therapy Targets Resistant Tumors

MedicalResearch.com Interview with:

Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands

Dr. Peeper

Daniel S. Peeper, PhD
Professor of Functional Oncogenomics (VUmc)
Member of Oncode Institute
Head, Division of Molecular Oncology & Immunology
Chair, Scientific Faculty Council
Chair, Translational Research Board
The Netherlands Cancer Institute
Amsterdam The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting.

Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  Continue reading

Multiple Sclerosis: Rituximab Had Better Short and Medium Term Outcomes

MedicalResearch.com Interview with:
Fredrik Piehl MD PhD, prof. of Neurology

Neuroimmunology Unit. Dept Clinical Neuroscience
Neurology Dept.
Karolinska University Hospital (Solna)
Stockholm

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years we have seen a drastic increase in treatment options for relapsing-remitting multiple sclerosis (RRMS). However, it is difficult to deduce long term performance of different drugs based only on data from randomized controlled trials, since such trials are performed in selected patients without major co-morbidities and perhaps also enriched for those with a milder disease course. In addition, most trials only last for two years and lack relevant comparators. This lack of knowledge makes it difficult to predict if a drug will work or not for a given patient, in turn leading to frequent treatment switches but also different treatment practices across countries, regions or even between centers. This is also the case in Sweden, but with the additional aspect that some regions have opted to treat most newly diagnosed RRMS patients with rituximab (Rituxan/Mabthera), a drug not formally approved for RRMS, but with extensive safety data from other indications.

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Oral Immunotherapy With Omalizmuab Resulted in Faster Food Desensitization

MedicalResearch.com Interview with:

Sandra Andorf PhD Kim and Ping Li Director of Computational Biology Sean N. Parker Center for Allergy and Asthma Research at Stanford University Instructor, Nadeau Lab Department of Medicine, Division of Pulmonary & Critical Care Medicine Stanford University School of Medicine

Dr. Andorf

Sandra Andorf PhD
Kim and Ping Li Director of Computational Biology
Sean N. Parker Center for Allergy and Asthma Research at Stanford University
Instructor, Nadeau Lab
Department of Medicine, Division of Pulmonary & Critical Care Medicine
Stanford University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Food allergies are on the rise in the world. Approximately 15 million Americans have food allergies, which includes around 6 million children. Of people with food allergies, 30-40% are allergic to more than one food and therefore these people have a greater risk for an accidental ingestion resulting in an allergic reaction or anaphylaxis.

Currently there is no FDA approved treatment for food allergies but oral immunotherapy, a treatment in which the patient eats small but slowly increasing doses of their allergen until they can tolerate a specified dose, was shown in research settings to be safe in children and adults for up to 5 foods in parallel.

In this trial, we studied the efficacy and safety of Omalizmuab (an anti-IgE drug) treatment with oral immunotherapy in multifood allergic participants versus placebo with oral immunotherapy for a total of 9 months. We found that 83% of the participants who received Omalizumab could tolerate at least 2 g of at least two different food allergens at the end of the trial compared to 33% of those who received placebo. The participants that received Omalizumab were also desensitized faster, meaning they were on average able to eat 2 g of each of their allergic foods earlier in the treatment. Furthermore, we could show that the use of Omalizumab and the fast updosing is safe.

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Ovarian Cancer Trial: Disappointing Results of Paclitaxel With/Without Pazopanib

MedicalResearch.com Interview with:
Debra Richardson, MD, FACOG, FACS
Associate Professor, Section of Gynecologic Oncology,
Oklahoma TSET Phase I Program
Stephensen Cancer Center
The University of Oklahoma

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer.

This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype.

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Multiple Myeloma: Phase 3 Study of DARZALEX + VMP Reduced Risk of Disease Progression and Mortality

MedicalResearch.com Interview with:

Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece

Dr. Dimopoulos

DrMeletios A. Dimopoulos MD
Professor and Chairman
Department of Clinical Therapeutics
University Athens School of Medicine
Athens, Greece

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone.

DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December.

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FDA Grants IND of ARTEMIS™ T cell Platform To Enhance CAR-T Cancer Therapies Without Cytokine Storm

MedicalResearch.com Interview with:
Dr. Cheng Liu PhD
President and Chief Executive Officer of Eureka Therapeutics.

MedicalResearch.com: What is the background for this study? What are the main findings?

 

    • Eureka Therapeutics, Inc. is a clinical stage biotechnology company focused on improving the safety profile of T cell therapies and developing novel T cell therapies for the treatment of solid tumors.
    • ET190L1-ARTEMISTM utilizes Eureka’s proprietary ARTEMISTM T cell receptor platform and proprietary human anti- CD19 binder to target CD19-positive malignancies. In preclinical studies, ET190L1-ARTEMISTM matched the cancer killing potency of current CAR-T therapies but with a dramatic reduction in the levels of inflammatory cytokines released, a main cause of cytokine release syndrome. In addition, these studies have shown that ET190L1-ARTEMISTM T cells are less exhausted and more naive and therefore, expected to have improved persistence in vivo. If confirmed in the clinic, this could result in a longer term therapeutic benefit to patients with an improved safety profile.
    • Eureka is also focused on developing the next evolution of T cell therapies against solid tumors which represent 90% of all cancers. While CAR-T therapies have been successful with liquid tumors such as leukemia and lymphoma, they have not been successful in solid tumors because of a lack of specific cell surface antigens. Eureka has pioneered the use of TCR mimic antibodies to target intracellular antigens in solid tumors that were once considered undruggable. Using its proprietary human E-ALPHA® phage display library, Eureka has discovered highly-specific, high affinity TCR mimic antibodies that can target intracellular antigens in solid tumors when processed into peptides and presented onto the cell surface by the MHCI complex. Pre-clinical studies have shown that when these TCR mimic antibodies were engineered onto the ARTEMISTM or CAR-T cell receptor platform against hepatocellular carcinoma (liver cancer) cells, the T cells launched a potent anti-tumor response.

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MedImmune’s MEDI9197 Activates Immune System To Fight Tumors

MedicalResearch.com Interview with:

Dr. Koustubh Ranade, Vice President of Research & Development Translational Medicine MedImmune

Dr. Ranade

Dr. Koustubh Ranade, PhD
Vice President of Research & Development Translational Medicine
MedImmune

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In a healthy person, abnormal cells including cancer cells are typically detected and destroyed by the immune system in response to danger signals activated by the abnormal cells. However, some solid tumors avoid triggering danger signals, and thus the immune system cannot recognize and destroy cancer cells, permitting tumor growth. To help activate the patient’s immune system to fight these “hidden” cancer cells, MedImmune scientists have developed MEDI9197, a TLR 7/8 agonist, to trigger the needed danger signals.

Our latest data from the Phase 1 study of MEDI9197 demonstrated that through intratumor injection, the therapy binds to TLR7 and TLR8 receptors and activates dendritic cells, which call in other immune cells to fight the tumor.

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Treatment With Tremfya® (Guselkumab) Improved Psoriatic Arthritis Symptoms Through One Year

MedicalResearch.com Interview with:

Atul A. Deodhar, MD, MRCP, FACP, FACR Professor of Medicine Division of Arthritis & Rheumatic Diseases Medical Director, Rheumatology Clinics Medical Director, Immunology Infusion Center Oregon Health & Science University (OHSU) 

Dr. Deodhar

Atul A. Deodhar, MD, MRCP, FACP, FACR
Professor of Medicine
Division of Arthritis & Rheumatic Diseases
Medical Director, Rheumatology Clinics
Medical Director, Immunology Infusion Center
Oregon Health & Science University (OHSU) 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Phase 2, randomized, double-blind, placebo–controlled, multicenter trial was designed to evaluate the efficacy and safety of guselkumab (Tremfya®) compared with placebo in adults with active psoriatic arthritis, despite having received treatment with standard-of-care therapies, including anti-tumor necrosis factor (TNF)-alpha agents.

In an observed analysis presented at ACR 2017, more than 70 percent of patients receiving guselkumab achieved at least a 20 percent improvement in signs and symptoms of disease (ACR 20) at week 56.  Findings also showed that improvements in tender and swollen joints, skin clearance, pain and physical function, and patient-reported quality of life outcomes reported at week 24, were maintained through week 56 in patients receiving guselkumab maintenance therapy (subcutaneous injections every eight weeks).  Continue reading