Author Interviews, Cancer Research, Microbiome / 07.03.2024

MedicalResearch.com Interview with: Dr Ashray Gunjur MBBS (Hons), B. Med Sci, MPHTM FRACP Clinical Research Training Fellow Melbourne, Australia   MedicalResearch.com: What is the background for this study? Response: As background, the last ~5 years have seen a surge of interest in the relationship between gut microbiota and cancer response to immune checkpoint blockade (ICB). We know that though a fraction of many different cancer types will respond to these therapies, it is currently very hard to predict who that will be- so ‘microbiome’ based biomarkers to select patients, or even strategies to change a patient’s microbiome to enhance their chance of responding, are very attractive. A key challenge, however, has been a lack of consistency in the microbes associated with response or non-response across different studies from different regions. While geographic, methodological, and technical variation likely contribute to this, most studies examined the gut microbiome at a genus- or species- taxonomic rank level, while we know there is significant intra-species (strain-level) diversity. As such, one of our key research questions was whether we could improve the reproducibility of microbial ‘signatures’ of response across cohorts using higher resolution approaches- with our hypothesis being that strain-resolution signatures would outperform species- or lower resolution signatures. We obtained our signature by analysing baseline faecal samples from the CA209-538 clinical trial, a wonderful investigator-initiated study sponsored by the Olivia Newton-John Cancer Research Institute (Melbourne, Australia). I was fortunate enough to work on this trial as a clinical investigator while training to be a medical oncologist. (more…)
ASCO, Author Interviews, Cancer Research, Lung Cancer, University of Pennsylvania / 05.06.2023

MedicalResearch.com Interview with: Lova L. Sun, MD, MSCE Medical Oncology Assistant Professor of Medicine Hospital of the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: An common clinical question for patients with metastatic non-small cell lung cancer with long-term response to immunotherapy-based treatment is how long to continue treatment. The major clinical trials stopped immunotherapy at a maximum of 2 years, but in clinical practice many patients and clinicians continue treatment beyond this time point. We conducted a retrospective study of lung cancer patients across the US with long-term response to immunotherapy, to compare survival between those who stopped treatment at 2 years vs those who continued beyond 2 years. We found that there was no statistically significant difference in survival between the two groups. (more…)
Author Interviews, Cancer Research, Immunotherapy, Melanoma, Science, UT Southwestern / 22.03.2023

MedicalResearch.com Interview with: Andrew Y. Koh, M.D. Associate Professor, Pediatrics and Microbiology University of Texas Southwestern Medical Center Director of Pediatric Cellular and ImmunoTherapeutics Program University of Texas Southwestern Medical Center and Children's Health MedicalResearch.com: What is the background for this study? Response: We asked the basic question how does a bacteria in your gut help your immune system fight a cancer outside the gut (extraintestinal tumor).  Based on work that our group and others have published in the infectious diseases, microbiology, and inflammation fields, we knew that certain conditions (e.g. inflammation, infection) promote gut microbiota to move from the gut to the mesenteric lymph nodes.  So we hypothesized that immune checkpoint therapy (which essentially induces inflammation to promote tumor killing) might induce gut microbiota translocation to the mesenteric lymph nodes and that this might be the first step by which gut bacteria can engage with host immune cells.  (more…)
Author Interviews, Cancer Research, Immunotherapy / 17.12.2020

MedicalResearch.com Interview with: Joshua Brody MD Director, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine New York, New York 10029 MedicalResearch.com: What is the background for this study?   Response: Cancer Immunotherapies target "antigens" on the surface of cells. -CAR-T cells targets antigens e.g. CD19 -Bispecific antibodies target antigens e.g. CD20 -Anti-PD1 antibodies awaken T cells that target antigens on e.g. MHC-I Cancer Immunotherapies frequently fail because a small percent of tumor cells simply lack the antigen and cause cancer relapse ('Antigen Escape') (more…)
Author Interviews, Cancer Research, Immunotherapy / 05.12.2020

MedicalResearch.com Interview with: Dr. Corina Dutcus MD Vice President of Clinical Research Oncology Business Group Eisai MedicalResearch.com: What is the background for this study? Would you briefly explain how lenvatinib works? Is it used for any other malignancies, ex. thyroid cancer? Dr. Corina Dutcus Response: LENVIMA (lenvatinib), discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. LENVIMA is approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. The approved starting dose for LENVIMA is 18 mg daily. The objective of Study 218, a randomized, open-label, Phase 2 trial, was to assess whether the lower starting dose of LENVIMA (14 mg daily) in combination with everolimus (5 mg daily) would provide similar efficacy with an improved safety profile compared to the FDA-approved starting dose of LENVIMA (18 mg daily) plus everolimus (5 mg daily) in patients with advanced renal cell carcinoma (RCC) following prior treatment with an antiangiogenic therapy. In the US, LENVIMA is also indicated for:
  • the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC);
  • for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC);
  • and in combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf. (more…)
Allergies, Author Interviews, Immunotherapy, Pediatrics / 04.12.2020

MedicalResearch.com Interview with: Lianne Soller, PhD Allergy Research Manager BC Children’s Hospital Allergy Clinic Vancouver, BC, Canada MedicalResearch.com: What is the background for this study? Response: Peanut oral immunotherapy (also known as OIT) has been studied for many years in clinical trials and has been found to be safe and effective in preschoolers. However, we know that clinical trials do not always reflect what happens in the real world. We wanted to see study whether peanut OIT would work as well in the real world. This is a follow up of our preschool peanut OIT safety study published in April 2019 which noted only 0.4% severe reactions and 4% epinephrine use during build-up. (more…)
Author Interviews, Cancer Research, Dermatology, Pediatrics / 16.09.2020

MedicalResearch.com Interview with: Irene Lara-Corrales, MD Associate Professor of Pediatrics at the University of Toronto Staff physician in Pediatric Dermatology at the Hospital for Sick Children in Toronto, Canada She is a member of the Society for Pediatric Dermatology.   Christina Boull, MD Assistant Professor of Dermatology at the University of Minnesota Program Director for the Advanced Dermatology Medical Student Rotation Fellowship Director for the Pediatric Dermatology Fellowship     MedicalResearch.com: What is the background for this study? Response: We got involved in this project a couple of years ago when many members of the Pediatric Dermatology Research Alliance's (PeDRA) Skin Tumors and Reactions to Cancer Therapies (STARC) group started seeing many patients with skin toxicities given by targeted therapies.  We recognized that this was a new and growing area of skin concerns that pediatric dermatologists were starting to see. Being such a new field, and with little known about these medications, we thought it would be important to put our cases together and describe what we were seeing.   (more…)
Author Interviews, ESMO, Immunotherapy, Melanoma, NEJM / 03.09.2020

MedicalResearch.com Interview with: Reinhard Dummer, Prof. Dr. med. Stv. Klinikdirektor Universitätsspital Zürich, Dermatologische Klinik Zürich MedicalResearch.com: What is the background for this study? Response: Based on molecular biology analysis, a substantial proportion of melanomas are driven by mutations of BRAF resulting in an ongoing growth activating signal. Based on the key role of BRAF several multiple kinase molecules have been developed in order to target this crucial pathway. These medications have shown to improve progression free survival and overall survival in advanced metastatic melanoma. Because there is a tendency for improved outcome in patients with low tumor burden, combined targeted therapy using Dabrafenib and Trametinib have been investigated in the adjuvant (after complete surgical resection) setting in stage III melanoma. And the 5 year data are now available in the New England Journal of Medicine. (more…)
Author Interviews, Biomarkers, Cancer Research / 20.08.2020

MedicalResearch.com Interview with: Dr. Alexey Aleshin, M.D., MBA Senior Medical Director Natera MedicalResearch.com: What is the background for this study? Response: Checkpoint inhibitor-based immunotherapies (ICI)  have changed the management of a range of cancers of diverse histologies. While these therapies are well tolerated and efficacious, only a minority (<20%) of patients respond to treatment or derive durable clinical benefit from them, highlighting the need for a pan-cancer biomarker that can predict response prior to, or shortly after, treatment initiation. With immune checkpoint inhibitors (ICIs) rapidly becoming a cornerstone of cancer therapy, early determination of response to ICI treatment can optimize patient benefit and minimize the risk of toxicities, while potentially reducing unnecessary treatment and costs to patients and payers. Additionally, due to the nature of immune checkpoint inhibition, atypical patterns of response have emerged. For instance, tumor pseudoprogression — a transient increase in tumor size due to the infiltration of immune cells, followed by delayed shrinkage — has been reported in as much as 10% of patients receiving ICI therapy. Distinguishing pseudoprogression from true progression is clinically important to avoid premature discontinuation of a treatment that may have future benefit, or delay the initiation of an alternative line of therapy. However, they are hard to differentiate using current imaging techniques. Our study published in Nature Cancer earlier this month, demonstrates that bespoke circulating tumor DNA (ctDNA) testing may be a valuable tool that sheds light on both of these issues. (more…)
Author Interviews, Cancer Research, COVID -19 Coronavirus / 14.05.2020

MedicalResearch.com Interview with: AVM BiotechologyTheresa A. Deisher, Ph.D Founder and CEO Chariman of Board AVM Biotechnology Dr. Deisher discusses AVM Biotechnology’s plan to study the immune stimulator AVM0703, developed for it’s anti-tumor effects,  as a potential agent to combat COVID-19.  MedicalResearch.com: What is the background for this study? What is AVM0703 currently being studied to treat?   Response: Our lead small molecule, AVM0703, is a novel, patent-pending repurposed formulation of an active pharmaceutical ingredient that has been U.S. Food and Drug Administration (FDA)-approved since 1961. AVM0703 works by supercharging and mobilizing immune cells, including a novel natural killer T-cell (NKT), novel cytotoxic T lymphocytes and a CD11b very high dendritic cell, which invade and destroy tumors more effectively than untreated immune cells. AVM Biotechnology has received clinical trial approval from the FDA to begin Phase I/II trials to characterize the safety, tolerability, pharmacokinetics, and antitumor activity of AVM0703 administered as a single intravenous infusion to pediatric and adult patients (≥12 years old) with terminal, no-option lymphoid malignancies. In addition, we are planning to study AVM0703 in Phase I/II trials in patients with severe or life-threatening COVID-19 infection. The proposed study is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous infusion. The study’s objective is to evaluate the safety and efficacy of AVM0703 in patients with COVID-19, as well as assess pharmacokinetics and dosing, including the maximum tolerated dose and the recommended Phase II dose. We hope to begin recruiting patients next month (June 2020). (more…)
ASCO, Author Interviews, Cancer Research, Journal Clinical Oncology / 10.04.2020

MedicalResearch.com Interview with: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Would you explain what is meant by switch maintenance immunotherapy? Response: For decades, platinum-based chemotherapy has been standard first-line treatment for metastatic urothelial (bladder) cancer. The standard approach to first-line chemotherapy is to administered approximately 6 cycles of treatment (in the absence of disease progression or prohibitive side effects), and then to stop treatment and monitor. Unfortunately, virtually all patients with metastatic disease will experience disease progression after stopping chemotherapy. However, we know that if we just continue the same platinum-based chemotherapy until progression of cancer (rather than stopping after ~6 cycles), the side effects continue to accumulate but the benefits plateau. Approximately 5 years ago, the first new systemic therapies were approved to treatment metastatic urothelial cancer in decades, immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors). In fact, 5 PD-1/PD-L1 inhibitors have been approved by the FDA for the treatment of patients with metastatic urothelial cancer progressing despite prior platinum-based chemotherapy. Given that these drugs are non-cross resistant with chemotherapy in at least a subset of patients (i.e., they can provide benefit even when chemotherapy is no longer working), and because they are well tolerated by a large proportion of patients, a logical question is rather than waiting until cancer progresses after stopping first-line chemotherapy, what if we started immunotherapy immediately. Switch maintenance refers to switching from chemotherapy to a different class of drug (e.g., immunotherapy) and maintenance refers to trying to "maintain" the response achieved with initial chemotherapy. (more…)
Author Interviews, Nature / 22.11.2019

MedicalResearch.com Interview with: Dr. Gary J. Nabel M.D., Ph.D. Chief Scientific Officer, Global Research and Development Sanofi MedicalResearch.com: What is the background for this study? Response: The power of T cell co-stimulation in the immune system became apparent to the immunology community from basic studies on T cell activation and T cell receptor function dating back to the 1980’s and 1990’s.  As a professor at the University of Michigan and investigator at its Howard Hughes Medical Institute in the 1990’s, I became aware of this pathway through collaborations with Carl June and Craig Thompson in the 1990s.  When we stimulated T cells by engaging CD3 (a T cell receptor activation signal e.g. signal 1) and CD28 (a survival signal e.g. signal 2), we found that the co-stimulatory effect led to exceptional T cell proliferation. After our Sanofi team developed the trispecific antibody technology, we realized that it might be possible to engage CD3 and CD28 while targeting T cells to tumors with a third arm, CD38, which is highly expressed on myelomas, all interactions mediated by this one protein.  (more…)
Allergies, Author Interviews, Pediatrics, Pharmaceutical Companies / 21.08.2019

MedicalResearch.com Interview with: Todd Green MD Vice President of Medical Affairs North America DBV Technologies https://www.dbv-technologies.com   Dr. Green discusses the recent announcement that DBV Technologies is submitting a BLA for Viaskin Peanut to the FDA.   MedicalResearch.com: What is the background for this announcement? How common is peanut allergy in children?  DBV Technologies is a global clinical-stage biopharmaceutical company whose mission is to improve the lives of patients with food allergies and other immunological diseases through our investigational epicutaneous immunotherapy technology platform. For more than 15 years, we’ve been striving to deliver transformative treatments for patients suffering with the burden and life-threatening risk of food allergies. On August 7, 2019 DBV announced the submission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration for Viaskin® Peanut for the treatment of peanut-allergic children ages 4 to 11 years. This submission addressed the additional data needed on manufacturing procedures and quality controls which were communicated by the FDA in December 2018, when DBV voluntarily withdrew its prior BLA submission for Viaskin Peanut. Peanut allergy is one of the most common food allergies and can cause severe, potentially fatal allergic reactions, including anaphylaxis. In the United States, nearly one million children suffer from a peanut allergy.[1] Fear of life-threatening reactions triggered by accidental peanut exposure during everyday activities may lead to significantly increased anxiety and decreased quality of life for patients and their families.[2,3,4] Currently, avoidance and readiness to manage accidental exposure reactions remain the standard of care. At DBV, we are committed to finding treatments that will help address the urgent unmet medical need of those suffering from food allergies, including peanut allergy, and our mission is to improve the lives of those patients and their families. (more…)
Allergies, Author Interviews, Immunotherapy, Pediatrics / 18.04.2019

MedicalResearch.com Interview with: Lianne Soller, PhD Allergy Research Manager University of British Columbia Vancouver, BC, Canada   MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2017, a clinical trial of 37 subjects demonstrated that preschool peanut oral immunotherapy was safe, with predominantly mild symptoms reported and only one moderate reaction requiring epinephrine. Our study aimed to examine whether these findings would be applicable in a real-world setting (i.e., outside of research). We found that peanut oral immunotherapy is safe in the vast majority of preschoolers, with only 0.4% of patients experiencing a severe reaction, and only 12 out of ~40,000 peanut doses needed epinephrine (0.03%).  (more…)
Allergies, Author Interviews, Immunotherapy, Lancet / 02.04.2019

MedicalResearch.com Interview with: Arnon Elizur MD Director, The Institute of Allergy, Immunology & Pediatric Pulmonology Yitzhak Shamir Medical Center Zerifin, Israel MedicalResearch.com: What is the background for this study?   Response: Tree nuts are among the most common food allergies and are a major cause of fatal and near fatal reactions. Patients with tree nut allergy are often allergic to several nuts, further increasing the risk of accidental exposures, dietary limitations, and the emotional burden and anxiety in affected patients. In the past 10 years, oral immunotherapy (OIT) has shown promise as a treatment modality for milk, egg and peanut allergies. However, limited data exists on oral immunotherapy for tree nuts and the treatment is complicated by the high prevalence of co-allergy to several nuts. (more…)
Abbvie, Author Interviews, Dermatology, Immunotherapy / 11.03.2019

MedicalResearch.com Interview with: Anne Robinson, Pharm D Executive Scientific Director AbbVie MedicalResearch.com: What is the background for the risankizumab data presented at the American Academy of Dermatology 2019 Annual Meeting? Response: Abstracts presented by AbbVie at the American Academy of Dermatology (AAD) 2019 Annual Meeting highlight additional data from the Phase 3 clinical trial program evaluating the safety and efficacy of risankizumab, an investigational interleukin-23 (IL-23) inhibitor. The registrational program for risankizumab evaluated more than 2,000 adult patients with moderate to severe plaque psoriasis across four pivotal studies. (more…)
Author Interviews, Immunotherapy / 04.03.2019

MedicalResearch.com Interview with: Edwin Kim, MD MS Assistant Professor of Medicine Division of Rheumatology, Allergy and Immunology Director, UNC Allergy and Immunology Clinic University of North Carolina at Chapel Hill Chapel Hill, NC  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background is that egg allergy remains one of the most common food allergies in childhood and although most patients will outgrow the allergy, it seems that many will carry into their teen years. As a result patients still have many years of risk of anaphylaxis, poor quality of life and potential nutritional deficits. The ability to introduce some amount of egg into the diet could have profound benefit to allergy patients. The main findings are that after completing up to 4 years of egg oral immunotherapy (OIT), most patients are able to introduce at least baked egg products into the diet. The subset of patients who showed a lasting benefit by passing a food challenge 4-6 weeks after stopping the OIT, generally did even better by being able to introduce lightly cooked egg like scrambled, boiled, or fried in addition to baked egg products. This benefit to the diet seemed to last up to 5 years after stopping egg oral immunotherapy. In addition to the safety, quality of life and nutrition benefits, recent data suggesting that bringing baked egg into the diet can speed up outgrowing the allergy provides a further benefit. (more…)
Allergies, Author Interviews, Immunotherapy / 25.02.2019

MedicalResearch.com Interview with: Dr Paul Turner FRACP PhD MRC Clinician Scientist and Clinical Senior Lecturer, Imperial College London Honorary Consultant in Paediatric Allergy & Immunology Imperial College Healthcare NHS Trust Hon Consultant, Royal Free Hospital / Royal Brompton & Harefield NHS Foundation Trust Clinical trials specialist (Paediatrics), Public Health England Clinical Associate Professor in Paediatrics, University of Sydney, Australia Dr. Nandinee Patel, MD Section of Paediatrics Imperial College London London, United Kingdom MRC & Asthma UK Centre in Allergic Mechanisms of Asthma London, United Kingdom MedicalResearch.com: What is the background for this study? Response: Current desensitisation protocols for peanut allergy use defatted roasted peanut flour, which can be difficult to accurately measure in very low doses needed for desensitisation (and thus has resulted in the development of AR101 by Aimmune which is likely cost many thousands of dollars for a course of treatment). We have previously observed that some children with food allergy to roasted peanut (such as peanut butter) are nonetheless able to tolerate boiled peanuts without reacting. We performed in vitro protein analysis studies which demonstrated that boiling peanuts resulted in around 50% of protein leaching out of the peanut into the cooking water. Furthermore, we found evidence for preferential leaching of allergen epitopes such as Ara h 2 as well aggregation of proteins resulting in a hypoallergenic peanut product. We therefore sought to assess whether boiled peanuts could be as effective and safe to induce desensitisation. (more…)
Author Interviews, HIV, Immunotherapy / 21.12.2018

MedicalResearch.com Interview with: Tatiana Garcia-Bates, Ph.D. Research Assistant Professor Department of Infectious Diseases and Microbiology Graduate School of Public Health University of Pittsburgh MedicalResearch.com: What is the background for this study? Response: Human immunodeficiency virus (HIV) infection is now a manageable disease with the advent and availability of highly effective, combination antiretroviral therapy (ART). Unfortunately, as soon as ART is interrupted, the virus quickly rebounds to high levels and again targets the immune system. Therefore, new immunotherapeutic treatments are sought to re-program the immune system to control the virus after ART interruption. In many ways, chronic HIV infection, even when controlled, resembles cancer in how it impacts the immune system. Both conditions for example are associated with immune dysfunction, where the immune cells (specifically T cells) that are supposed to protect our bodies against invading microorganisms or cancers become exhausted and fail to respond effectively. In cancer, effective immunotherapies have been developed to reverse this immune exhaustion to extend the fighting capacity of the T cells. An example of this is drugs that target immune checkpoints, or “shut down” proteins, expressed on activated T cells, such as the programmed death-1 (PD-1) receptor. When engaged, PD-1 sends a negative signal to deactivate the T cell, and this contributes to the immune exhaustion seen in both cancer and in chronic infections. Some cancers express the ligand or the “trigger” for this shut down receptor, called PD-1 ligand (PD-L1). When this interaction between PD-1 and PD-L1 is interrupted, for example by using a blocking antibody, T cells can regain their killing capacity and destroy infected cells or cancer cells. This anti-PD-1 therapy has demonstrated high success against a variety of tumors. Therefore, we tested this approach in the context of HIV infection using a well-characterized cohort of HIV-positive individuals to see if we could improve their T cell responses to HIV in a laboratory setting. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis / 27.11.2018

MedicalResearch.com Interview with: Dietmar P. Berger, MD, PhD Head of Global R&D Atara Biotherapeutic MedicalResearch.com: What is the background for this study? Response: Epstein-Barr virus (EBV) is present in B lymphocytes, plasma cells and epithelial cells of over 95% of individuals over the age of 40.  Multiple studies have shown that nearly all patients with Multiple Sclerosis (MS) are EBV positive, including a recent presentation at the 2018 ECTRIMS Congress in Berlin that showed 100% of MS patients are positive for EBV (Ruprecht et. al). Current B cell directed therapies such as anti-CD20 therapies have demonstrated an effect on  Multiple Sclerosis activity. These therapies work by depleting B cells including those infected by EBV. Our belief is that loss of EBV-specific T cell function (e.g., T cell exhaustion) occurs in patients who develop Multiple Sclerosis, which results in the accumulation of EBV infected B and plasma cells in the CNS leading to the autoreactive immune cycle seen in MS patients. The increasing evidence of a link between EBV infection and the development of MS led to the initiation of a Phase 1 study to investigate the use of an autologous T-cell immunotherapy (ATA190) to selectively target and deplete EBV infected cells in patients with progressive MS. As T cell immunotherapies (like ATA190) are designed to penetrate the central nervous system, this approach was felt to be particularly useful in  Multiple Sclerosis where the inflammatory response and infected B lymphocytes and plasma cells are inaccessible inside the CNS to the vast majority of classic targeted agents. (more…)
Author Interviews, Immunotherapy, Pancreatic / 14.11.2018

MedicalResearch.com Interview with: Dr James Kuo, MBBS Medical oncologist and Deputy Medical Director Scientia Clinical Research Sydney, Australia MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Immune checkpoint inhibitors (ICI) that have seen success in the treatment of patients with various tumour types have not been as effective in patients with metastatic pancreatic cancer and therefore immune-therapeutic agents of novel mechanism of action, in particular in combination with existing ICI, need to be investigated. This study set out to test the safety and efficacy of pixatimod, a novel immunomodulatory agent, in combination with nivolumab, firstly in the dose escalation cohorts in patients with any solid tumour for the maximal tolerable dose, and then using this dose to further treat an expansion cohort of patients with pancreatic cancer. Altogether 16 patients had received the combination and in 10 patients in whom treatment response was evaluable, 4 patients experienced a clinical benefit and continued treatment in the trial, with 1 patient having a significant partial response now treated for 48 weeks. Interestingly, all these 4 patients had metastatic colorectal cancer. Side effect profile has been consistent with other immunotherapeutic agent combination and in the patients who had clinical benefit, no treatment related side effects were observed.  (more…)
Asthma, Author Interviews, FDA, Regeneron / 31.10.2018

MedicalResearch.com Interview with: RegeneronNeil Graham,  M.B.B.S., M.D., M.P.H VP of Immunology & Inflammation Regeneron MedicalResearch.com: What is the background for this announcement?  Response: Patients with moderate-to-severe asthma often have uncontrolled, persistent symptoms despite standard-of-care therapy that may make them suitable for treatment with a biologic therapy. They live with coughing, wheezing and difficulty breathing, and are at risk of severe asthma attacks that may require emergency room visits or hospitalizations. [i],[ii] Oral corticosteroids can provide relief for severe, short-term symptoms. However, their chronic use is limited to the most severe patients due to the potential for serious side effects. [iii],[iv] A particular type of inflammation contributes to the cause of uncontrolled symptoms in multiple inflammatory diseases such as asthma and atopic dermatitis.[v] Dupixent is a medicine that inhibits the overactive signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that contribute to this type of inflammation. This inhibits cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE; however, the mechanism of action of Dupixent in asthma has not been definitively established. (more…)
Author Interviews, Cancer Research, Immunotherapy, JAMA, Vanderbilt / 13.09.2018

MedicalResearch.com Interview with: Douglas B. Johnson, M.D. Assistant Professor of Medicine Clinical Director, Melanoma Research Program Melanoma, clinical and translational studies Vanderbilt University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Immune checkpoint inhibitors produce long-lasting responses in patients with many different types of cancer. However, they may cause serious autoimmune-like side effects that may affect any organ. We used several large databases to determine how often these side effects were fatal, when they occurred, and which types of side effects were responsible. We found that overall, fatal side effects were uncommon, ranging from 0.3 – 1.3%. However, they tended to occur early on treatment (on average within the first 6 weeks), and affected a variety of organs, including the heart, lungs, colon, liver, and brain. There was a dramatic increase in reporting of fatal toxicities since 2017, likely reflecting the increased use of immune checkpoint inhibitors.  (more…)
Author Interviews, Leukemia / 11.09.2018

MedicalResearch.com Interview with: Hans van Eenennaam, Ph.D. Executive vice president antibody research and site head Aduro Biotech Europe MedicalResearch.com: What is the background for this study? Response: A PRoliferation Inducing Ligand (APRIL) is a member of the tumor necrosis factor superfamily and has been shown to stimulate the proliferation and survival of healthy B-lymphocytes. Malignant B-lymphocytes, such as multiple myeloma, use APRIL primarily in the bone marrow to support its proliferation and survival. Studies have shown that APRIL is overproduced in patients with multiple myeloma and mediates primarily via binding to B-cell maturation antigen (BCMA) to stimulate a wide variety of responses that promote multiple myeloma growth and survival, as well as suppressing the immune system so that the tumor cells are protected and sustained in the bone marrow and can escape current available treatments. (more…)
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, JAMA / 10.08.2018

MedicalResearch.com Interview with: Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years. Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice. There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy. (more…)
AACR, Author Interviews, Cancer Research, Pancreatic / 02.07.2018

MedicalResearch.com Interview with: Michael J. Pishvaian, MD, PhD Phase I Program Director Assistant Professor Lombardi Comprehensive Cancer Center Washington, DC 20007 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Pancreatic cancer is a deadly disease and will soon be the second leading cause of cancer-related death. We have made some progress in the last few years....but despite this, patients with advanced, inoperable pancreatic cancer (which represents about 80% of pancreatic cancer patients) still only live 12 months, on average. We desperately need new therapies, AND to think "outside the box" for the treatment of pancreatic cancer. In that context, we have been learning that there are subgroups of patients with cancer whose tumors are particularly susceptible to certain therapies - either new therapies, or in some cases, approved therapies that would have not normally been used for that disease.  These specific patient subgroups with "actionable" findings have been identified through extensive genetic and molecular characterization of a patient's tumor. In the past there was a cynical perspective that pancreatic cancer did not harbor any "actionable" molecular abnormalities. We have now demonstrated that: 1) There are clearly and undeniably patients with pancreatic cancer whose tumors do indeed harbor "actionable" findings.  This represents at least 27% of pancreatic cancer patients, but may represent up to 50% as new therapies evolve.  These percentages are also highly consistent with similar publications in the pancreatic cancer field over the last few years; and 2) Importantly, we have been following our patients longitudinally for outcomes, and while it is still early, there is a statistically significant improvement in progression-free survival when a patient with a specific actionable molecular abnormality is treated with the appropriately "targeted" therapy.  This finding is also consistent with findings that have been observed in other cancer types.   (more…)
Asthma, AstraZeneca, Author Interviews, Immunotherapy, Lancet, Pulmonary Disease / 27.06.2018

MedicalResearch.com Interview with: Reynold A. Panettieri, Jr., M.D. Professor of Medicine, Robert Wood Johnson Medical School Vice Chancellor, Clinical & Translational Science Director, Rutgers Institute for Translational Medicine & Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ  08901 MedicalResearch.com: What is the background for this study? Response: Severe asthma is characterized by Type 2 inflammation manifested by increases in IL-13, IL-4 and Il-5 levels in the airways that promotes airway hyperresponsiveness and in part irreversible airway obstruction.  These clinical manifestations profoundly increase asthma morbidity and mortality. To address an unmet therapeutic need, Tralokinumab was developed as a monoclonal antibody targeting soluble IL-13 with the goal of improving lung function and patient reported outcomes while decreasing annual exacerbation rates.  Stratus 1 and 2 represent two identical randomized, double-blind, placebo-controlled, phase 3 clinical trials in severe asthma.  These international trials enrolled approximately 2000 subjects with severe asthma and examined whether Tralokinumab decreased annualized exacerbation rates (AER) as compared with placebo (primary outcome). (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Duke, Immunotherapy, NEJM, Vaccine Studies / 26.06.2018

MedicalResearch.com Interview with: Annick Desjardins, M.D., F.R.C.P.C. Associate Professor of Neurology Associate Professor of Neurosurgery Director of Clinical Research The Preston Robert Tisch Brain Tumor Center at Duke Duke University School of Medicine Durham, NC 27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric). Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells. The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc. One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab. The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them. At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  (more…)
AACR, Aging, Author Interviews, Cancer Research, Immunotherapy, Melanoma / 21.06.2018

MedicalResearch.com Interview with: Ashani Weeraratna, Ph.D. The Ira Brind professor and Co-program leader of the Immunology, Microenvironment and Metastasis Program The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia  MedicalResearch.com: What is the background for this study? What are the main findings?  Response:  This study shows for the first time that older patients, especially those who have had prior MAPKi therapy fare better than younger patients when treated with anti-PD1. We found that tumors in younger patients and younger mice have higher levels of Tregulatory cells, the cells that regulate other immune cells. This is not true systemically, only within the tumor microenvironment. We were surprised because we expected that, as with targeted therapy, older patients would have a poorer response to immunotherapy, given what we perceive as a poorer immune system in older patients.  (more…)
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018

MedicalResearch.com Interview with: 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.  (more…)