Author Interviews, Cancer Research, Immunotherapy, NEJM, Transplantation / 19.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31344" align="alignleft" width="160"]Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021 Dr. Kenar Jhaveri,[/caption] Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy. In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject.
Author Interviews, Cancer Research, Immunotherapy, Nature, Technology, University of Michigan / 27.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30791" align="alignleft" width="168"]James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109 Dr. James Moon[/caption] James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109 MedicalResearch.com: What is the background for this study? Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach.
Author Interviews, Immunotherapy, Lancet, Lung Cancer / 23.12.2016

MedicalResearch.com Interview with: Dr Kiyotaka Yoh Department of Thoracic Oncology National Cancer Center Hospital East Kashiwa, Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: LURET is multicenter, single-arm, phase II study to evaluate the efficacy and safety of vandetanib as RET inhibitor in patients with advanced RET-rearranged non-small-cell lung cancer (NSCLC). In 2012, RET rearrangements were identified as rare oncogenic alterations for NSCLC. Among 17 eligible patients included in primary analysis, the objective response rate was 53% (95% CI 28–77), which met the primary endpoint. At the data cutoff, median progression-free survival was 4.7 months (95% CI 2.8–8.5). Overall, vandetanib was tolerated, with an adverse event profile similar to those seen in previous large population studies of vandetanib in patients with unselected NSCLC.
Author Interviews, Breast Cancer, Immunotherapy / 22.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30737" align="alignleft" width="125"]Joyce O'Shaughnessy, MD Co-Chair, Breast Cancer Research Texas Oncology-Baylor Charles A. Sammons Cancer Center Dr. Joyce O'Shaughnessy[/caption] Joyce O'Shaughnessy, MD Co-Chair, Breast Cancer Research Texas Oncology-Baylor Charles A. Sammons Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The MONALEESA-2 trial is a Phase III, randomized, double-blind, international study of LEE011 in combination with letrozole vs. letrozole alone, in postmenopausal women with HR+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease. Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experience recurrence of their initial breast cancer. We analyzed a pre-defined subgroup of women with de novo HR+/HER2- advanced breast cancer to better understand the response of LEE011 plus letrozole in this patient population. In the de novo advanced breast cancer patient sub-group, progression free survival was significantly prolonged; LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267–0.750]). The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone. Most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common all-grade adverse events (≥30% of patients with de novo advanced breast cancer) in the LEE011 plus letrozole arm were neutropenia (70.2%), nausea (48.2%), fatigue (42.1%), alopecia (39.5%), and leukopenia (31.6%).
Author Interviews, Cost of Health Care, Immunotherapy, Melanoma, Pharmacology / 22.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30744" align="alignleft" width="141"]Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR Dr. Herbert Loong[/caption] Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR MedicalResearch.com: What is the background for this study?  Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail. The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting.
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30711" align="alignleft" width="160"]Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030 Dr. Jerry Wolinsky,[/caption] Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030 MedicalResearch.com: What is the background for this study? Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses. However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval. The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016

MedicalResearch.com Interview with: Vince Giranda, M.D., PH.D. Project Director AbbVie Oncology Development MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate.
Author Interviews, Immunotherapy, Leukemia, Transplantation, University of Pennsylvania / 05.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30208" align="alignleft" width="132"]Dr. Alex Ganetsky Dr. Alex Ganetsky[/caption] Alex Ganetsky, PharmD, BCOP Clinical Pharmacy Specialist – Hematology/BMT Hospital of the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? • Allogeneic hematopoietic cell transplant (HCT) recipients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-GVHD) have poor outcomes. • There is no consensus for optimal treatment of these patients. • We retrospectively evaluated the efficacy of tocilizumab, an interleukin-6 receptor monoclonal antibody, for the treatment of steroid-refractory GI-GVHD. • 10/11 (91%) patients achieved a complete response after a median time of 11 days (range, 2 – 18) from tocilizumab initiation. • The median time to response onset, defined as improvement in GVHD stage by at least 1, was 1 day (range, 1 – 6). • At a median follow-up of 3 months (range, 1.1 – 12.8) from tocilizumab initiation, 8 of 11 patients are alive and free of the their underlying hematologic malignancy. • No associations between serum levels of IL-6 and tocilizumab response could be identified.
Author Interviews, Dermatology, Immunotherapy, Rheumatology / 28.11.2016

MedicalResearch.com Interview with: [caption id="attachment_30017" align="alignleft" width="96"]Atul Deodhar, M.D., M.R.C.P. Rheumatology Oregon Health and Science University Dr. Atul Deodhar[/caption] Atul Deodhar, M.D., M.R.C.P. Rheumatology Oregon Health and Science University  MedicalResearch.com: What is the background for this study? Response: Patients with psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS) are at an increased risk of developing inflammatory bowel disease (IBD) compared with the general population. It is important that we assess whether new therapies, including the recently approved interleukin-17A (IL-17A) inhibitor, secukinumab, have an acceptable profile in terms of the risk of IBD in patients with psoriasis, PsA, or AS.
Author Interviews, Immunotherapy, Multiple Sclerosis / 22.11.2016

MedicalResearch.com Interview with Ralph Kern, M.D. Senior vice president, Worldwide Medical Biogen MedicalResearch.com: What is the background for this study? Response: Previously reported clinical trials of daclizumab demonstrated significant efficacy across clinical and MRI measures, compared to placebo and interferon beta-1a 30 mcg intramuscular (IM) injection, and established the therapy’s safety profile for up to two to three years. These trials were the basis for approval by health authorities in the United States, European Union and Australia. Daclizumab is a once-monthly, self-administered, subcutaneous therapy for relapsing forms of MS (RMS). At ECTRIMS we presented the first interim results from EXTEND, a long-term extension study. EXTEND is an ongoing multicenter, open-label study to evaluate the safety and efficacy of daclizumab treatment in more than 1,500 patients with RMS. This interim ECTRIMS analysis includes up to five years of data from patients who were previously enrolled in DECIDE. DECIDE was a Phase 3 study evaluating the effects of daclizumab relative to interferon beta-1a IM. In the new analysis, patients who were treated with interferon beta-1a IM for two to three years in DECIDE switched to daclizumab when they enrolled in EXTEND, and were compared to daclizumab patients treated continuously in both DECIDE and EXTEND.
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 19.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29794" align="alignleft" width="200"]Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology Dr. Edith Perez[/caption] Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology MedicalResearch.com: What is the background for this study? What are the main findings? Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.
Author Interviews, Cancer Research, Immunotherapy / 17.11.2016

MEDICALRESEARCH.COM INTERVIEW WITH: [caption id="attachment_29733" align="alignleft" width="160"]THOMAS W. DUBENSKY, JR., PH.D.</strong> CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. DR. THOMAS W. DUBENSKY, Jr.[/caption] THOMAS W. DUBENSKY, JR., PH.D. CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: This presentation highlights findings from multiple preclinical models evaluating ADU-S100 (also known as MIW815), Aduro Biotech’s investigational STING (Stimulator of Interferon Genes) Pathway Activator immunotherapy. The company is developing ADU-S100 in partnership with Novartis. ADU-S100 is a synthetic ‘off-the-shelf’ small molecule immune modulator that is designed to generate a response against a patient’s own unique set of cancer antigens. It does this through the activation of human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T-cell adaptive immune response. We conducted preclinical studies in a variety of preclinical models to better understand the potential mechanism of action of ADU-S100 and its potential for treating a variety of cancer types, both within the immediate tumor environment, as well as throughout the body. Data from these preclinical studies suggest the following:
  • Intratumoral injection of ADU-S100 activates the STING Pathway and induces both a durable local and systemic anti-tumor immune response as evidenced by induction of type I interferons (IFNs) and a CD8+ T-cell response.
  • ADU-S100 is able to induce tumor-specific memory mediated by immune cells (e.g. T-cells and NK-cells) whereby the immune system is able to eliminate specific cancerous cells upon their reintroduction without further therapy.
  • Combination of STING activation in the tumor microenvironment and an anti-PD-1 checkpoint inhibitor enhances antitumor efficacy activation of the STING pathway, resulting in the complete eradication of local and distal tumors.
Author Interviews, Cancer Research, Immunotherapy, Pediatrics, Rheumatology / 16.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29722" align="alignleft" width="170"]Timothy Beukelman, MD, MSCE Associate Professor of Pediatrics Division of Rheumatology and Division of Clinical Immunology & Rheumatology University of Alabama at Birmingham Dr. Timothy Beukelman[/caption] Timothy Beukelman, MD, MSCE Associate Professor of Pediatrics Division of Rheumatology and Division of Clinical Immunology & Rheumatology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? Response: In 2009 the US FDA issued a boxed warning about malignancies reported in children treated with TNF inhibitors but their analysis did not account for a possible malignancy risk from other medications of from the Juvenile idiopathic arthritis (JIA) disease process itself.
Author Interviews, Immunotherapy, JAMA, Melanoma / 15.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29273" align="alignleft" width="150"]Feng Xie, Ph.D.</strong> Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University Dr. Feng Xie[/caption] Feng Xie, Ph.D. Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences McMaster University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cutaneous melanoma, an aggressive and deadly form of skin cancer, in early stages is often cured with surgery alone. Most patients presenting with advanced-stage disease, however, are not candidates for surgery and drug therapy is the main course of treatment. Around 40-60% of melanomas have a mutation in the BRAF protein. Multiple effective first-line treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two established classes of drug therapies: targeted therapy and immunotherapy. Presently, it remains uncertain which is the optimal first-line treatment. In our network meta-analysis we evaluated 15 randomized controlled trials published between 2011 and 2015 assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6662 treatment naïve patients with lymph node metastasis not amenable to surgery or distant metastatic melanoma. We found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival. PD-1 inhibition was associated with the lowest risk of serious adverse events.
Annals Internal Medicine, Author Interviews, Dermatology, Immunotherapy / 15.11.2016

MedicalResearch.com Interview with: Dr. Morton Scheinberg, MD, PhD From Hospital Israelita Albert Einstein and Hospital AACD, São Paulo, and Clinica Dermatosineida, Maringa, Parana, Brazil. MedicalResearch.com: What is the background for this study? What are the main findings? Response: That universal hair loss associated with a localized autoimmune reaction on the cells involved with the hair follicles can be halted with tofacitinib.
Author Interviews, Cancer Research, Immunotherapy / 11.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29564" align="alignleft" width="75"]Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 Dr. Lotze[/caption] Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Adoptive cell therapy (ACT) with Tumor-infiltrating Lymphocytes (TIL) has shown promise in mediating cancer regression which rely on activation in vivo compared to other immunotherapies that utilize genetically modified T-cells. In TIL therapy, autologous administration of TIL expanded outside the body elicits a highly individualized, specific and potent attack against the tumor. Clinical trials conducted at the National Cancer Institute evaluating TIL therapy for the treatment of metastatic melanoma reported overall response rates of up to 56%. The durable responses observed in these metastatic melanoma patients as well as other patients with cervical cancer, cholangiocarcinoma, and head and neck cancer signal the potential for broader application of TIL therapy to treat patients with other solid tumors, currently an area of substantial unmet clinical need. Lion’s study, recently presented at the Society for Immunotherapy of Cancer, sought to demonstrate the feasibility of culturing and expanding TIL isolated from non-melanoma tumors. We were successful in culturing TIL from tumors obtained from bladder, cervical, head and neck, lung and triple negative breast cancer.
Author Interviews, Cancer Research, Immunotherapy, Vaccine Studies / 09.11.2016

MedicalResearch.com Interview with: Leslie Chong Imugene Chief Operating Officer Armadale, Australia Leslie Chong Imugene Chief Operating Officer Armadale, Australia   MedicalResearch.com: What is the background for this study? How does HER-Vaxx work? • The technology originates from the Medical University of Vienna, one of Europe’s leading cancer institutes and was identified in 2012 by Dr Axel Hoos (Currently Sr. Vice President of Oncology R&D at GlaxoSmithKline, previous Clinical Lead on Ipilumimab at Bristol-Myers Squibb, a director at Imugene; his only Board seat worldwide) • HER-Vaxx is a peptide vaccine designed to treat tumours that over-express the HER2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. The vaccine is constructed from various B Cell epitopes of HER2/neu. It has been shown in pre-clinical work and in a Phase 1 study to stimulate a potent polyclonal antibody response to HER2/neu, a commercially and clinically validated cancer target. HER-Vaxx’s successful Phase 1 study was in patients with metastatic breast cancer and the next stage of development will be a Phase 1b/2 study in patients with gastric cancer initiating in 2016.
Author Interviews, Immunotherapy, Pulmonary Disease / 08.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29484" align="alignleft" width="200"]Dr. Luca Richeldi MD PhD Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton United Kingdom Dr. Luca Richeldi[/caption] Dr. Luca Richeldi MD PhD Professor of Respiratory Medicine Chair of Interstitial Lung Disease University of Southampton United Kingdom MedicalResearch.com: What is the background for this study? What are the main findings? Response: The data presented at CHEST 2016 were from two post-hoc pooled analyses of the Phase III INPULSIS® trials that evaluated Ofev in idiopathic pulmonary fibrosis, or IPF. Both analyses, using different measures, demonstrate Ofev efficacy in a range of people with IPF, regardless of disease severity at the start of the trials. One analyses investigated the efficacy of Ofev on disease progression in subgroups of patients defined by their GAP (gender, age, physiology) stage. Based on the index, patients were categorized as either GAP stage I or II/III. The analysis showed a similar reduction in disease progression with Ofev versus placebo regardless of GAP stage – meaning no significant difference between GAP stage I versus GAP stage II/III. Disease progression was defined as an absolute decline in forced vital capacity (FVC) ≥5% predicted or death over 52 weeks.
Author Interviews, Dermatology, Immunotherapy / 04.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29402" align="alignleft" width="133"]Brett A. King, MD, PhD Assistant Professoro Department of Dermatology School of Medicine Yale University New Haven, CT 06520 Dr. Brett King[/caption] Brett A. King, MD, PhD Assistant Professor Department of Dermatology School of Medicine Yale University New Haven, CT 06520 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recent advances in the understanding of the pathogenesis of alopecia areata (AA) have yielded Janus kinase (JAK) inhibitors as a promising therapy. Short-term treatment with the JAK inhibitor, tofacitinib, has shown efficacy for severe AA, alopecia totalis (AT), and alopecia universalis (AU), but long-term data are lacking. In this retrospective series of patients aged 18 years or older treated with tofacitinib, of 65 potential responders to therapy, defined as those with AT or AU with duration of current episode of disease of 10 years or less or AA, 77% achieved at least some hair regrowth, with 58% of patients achieving greater than 50% change in SALT score and 20% of patients achieving complete scalp hair regrowth over 4 to 18 months of treatment. Tofacitinib was well tolerated, and there were no serious adverse events.
Author Interviews, HIV, Immunotherapy / 02.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29241" align="alignleft" width="168"]Jacob Lalezari, MD Quest Clinical Research San Francisco, CA Dr. Jacob Lalezari[/caption] Jacob Lalezari, MD Quest Clinical Research San Francisco, CA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • Tremendous strides have been made since HIV-1 was first discovered 35 years ago. However, while many HIV patients can control the infection with currently-approved therapies, there is an urgent need for new treatments that can address viruses that are resistant to multiple antiretroviral treatment classes. With people starting treatments earlier and staying on them longer, some patients also face long-term safety and tolerability issues associated with current therapies.
  • Thousands of people are infected with HIV-1 with resistance to three classes of antiretroviral therapy (ART), and are in dire need of treatment. There are limited or no treatment options available for these patients.
  • As multi-drug resistant (MDR) HIV can be transmitted, it is imperative that it be controlled in order to prevent it from becoming a larger problem. It is important to not only focus on the patient being treated but also consider those they could infect.
  • Ibalizumab is the first biologic long-acting investigational ART to show efficacy in patients in just seven days. The Phase III TMB-301 results showed that patients with MDR HIV-1 and with limited treatment options experienced a significant decrease in viral load after receiving a loading dose of ibalizumab (2,000 mg intravenously) in addition to their failing ART therapies.
    •  A total of 40 patients were enrolled in the study.
    • Seven days after the loading dose, 83% of patients achieved a ≥ 0.5 log10 decrease from baseline compared with 3% during the seven-day control period.
    • These results were statistically significant (p<0.0001). Moreover, during that same period, 60% achieved a decrease of ≥1.0 log10.
    • The average viral load decrease for the total population was 1.1 log10
    • There were no treatment-related serious adverse events or discontinuations reported during the initial seven-day treatment period. 
Author Interviews, ESMO, Immunotherapy, Lung Cancer / 21.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29030" align="alignleft" width="133"]Shirish Gadgeel, MD Leader of the Thoracic Oncology Multidisciplinary team Professor at Karmanos Cancer Institute Detroit Dr. Shirish Gadgeel[/caption] Shirish Gadgeel, MD Leader of the Thoracic Oncology Multidisciplinary team Professor at Karmanos Cancer Institute Detroit MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUX-Lung 7 is the first global, head-to-head trial comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib respectively) for patients with EGFR mutation-positiveNon-Small Cell Lung Cancer NSCLC who received no prior treatment. The Phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R). The trial's co-primary endpoints were progression-free survival (PFS) by independent review, time to treatment failure and overall survival (OS); and the secondary endpoints included ORR, disease control rate, tumor shrinkage, patient-reported outcomes and safety.
Author Interviews, Biomarkers, Immunotherapy, Pancreatic / 21.10.2016

MedicalResearch.com Interview with Dr. Ashton A. Connor, MD PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research Dr. Steven Gallinger MD, MSC Division of General Surgery Toronto General Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Response: The etiology of pancreatic ductal adenocarcinoma (i.e. "pancreatic cancer") and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood. Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer. With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours. Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge.
Author Interviews, Dermatology, Immunotherapy / 17.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28956" align="alignleft" width="200"]Dr. Alan Menter MD Texas Dermatology Associates Dr. Alan Menter[/caption] Dr. Alan Menter MD Texas Dermatology Associates MedicalResearch.com: What is the background for this study? Response: Psoriasis on the palms and soles of the feet—also known as palmoplantar psoriasis of which there are 2 variants, plaque type or pustular, —can significantly affect a person’s quality of life and is often difficult-to-treat with available treatments. Researchers in this study set out to determine the efficacy and safety of Taltz (ixekizumab) through 60 weeks among patients with moderate-to-severe plaque psoriasis with significant palmoplantar involvement. Plaque psoriasis is the most common form of psoriasis appearing as raised, red patches covered with a silvery white buildup of dead skin cells which are often painful or itchy. This study was an analysis of UNCOVER-3, a Phase 3, multicenter, double-blind, placebo-controlled trial. In the first 12 weeks of this study, patients were randomized to receive placebo, etanercept (50 mg, twice-weekly) or 80 mg of Taltz every two weeks or every four weeks, following an initial starting dose of 160 mg. At 12 weeks, all patients received open-label Taltz every four weeks through 60 weeks.
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 17.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28949" align="alignleft" width="150"]Melanie Royce, MD, PhD Professor of Medicine University of New Mexico School of Medicine Director of the Breast Multidisciplinary Clinic and Program UNM Cancer Center. Albuquerque, NM Dr. Melanie Royce[/caption] Melanie Royce, MD, PhD Professor of Medicine University of New Mexico School of Medicine Director of the Breast Multidisciplinary Clinic and Program UNM Cancer Center. Albuquerque, NM MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/HER2-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the Phase II BOLERO-4 clinical trial, presented as an oral presentation at the 2016 European Society for Medical Oncology (ESMO) annual meeting, show preliminary evidence that everolimus in combination with letrozole is effective in treating women with HR-positive/HER2-negative advanced breast cancer in the first-line setting. With follow up of 17.5 months, the median progression-free survival (PFS) is not yet reached. At six months, 83.6% (95% CI: 77.3-88.2%) of women taking everolimus plus letrozole in the first-line setting were without disease progression, and 71.4% (95% CI: 64.0%-77.5%) did not have disease progression at twelve months. Safety findings from BOLERO-4 are consistent with previous studies of everolimus in advanced breast cancer, with the most common adverse events being stomatitis (67.8%), weight loss (42.6%) and diarrhea (36.1%). These adverse events were mostly grade 1 or 2 in severity1.
Author Interviews, Cancer Research, ESMO, Immunotherapy, NYU/NYMC / 16.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28911" align="alignleft" width="200"]Arjun Balar, M.D. Assistant Professor of Medicine Director - Genitourinary Medical Oncology Program NYU Perlmutter Cancer Center New York, NY 10016 Dr. Arjun Balar[/caption] Arjun Balar, M.D. Assistant Professor of Medicine Director - Genitourinary Medical Oncology Program NYU Perlmutter Cancer Center New York, NY 10016 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Standard treatment for advanced urothelial cancer includes cisplatin-based chemotherapy which has been shown to improve survival. But more than half of patients are not expected tolerate it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative to cisplatin. Pembrolizumab is a PD-1 blocking antibody that reactivates the body’s cancer-fighting T-cells (part of the immune system) to fight urothelial cancer. The trial overall enrolled 374 patients who had not yet received any treatment for advanced urothelial cancer, but were considered ineligible for cisplatin chemotherapy.
Author Interviews, ESMO, Immunotherapy, Ovarian Cancer / 14.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28888" align="alignleft" width="120"]Mansoor Raza Mirza, MD Medical Director: Nordic Society of Gynecologic Oncology (NSGO) Board of Directors: Gynecologic Cancer Inter-Group (GCIG) Faculty: European Society of Medical Oncology (ESMO) Faculty: International Gynecologic Cancer Society (IGCS) Chief Oncologist, Rigshospitalet Copenhagen University Hospital Copenhagen, Denmark Dr. Mansoor Raza Mirza[/caption] Dr. Mansoor Raza Mirza, MD Medical Director: Nordic Society of Gynecologic Oncology Board of Directors: Gynecologic Cancer Inter-Group (GCIG) Faculty: European Society of Medical Oncology (ESMO) Faculty: International Gynecologic Cancer Society (IGCS) Chief Oncologist, Rigshospitalet Copenhagen University Hospital Copenhagen, Denmark MedicalResearch.com: What is the background for this study? Response: Recurrent ovarian cancer is an area of significant unmet medical need, and there have been few therapeutic advances for these patients in the past few decades. Niraparib was studied to provide patients with recurrent ovarian cancer an option other than “watchful waiting,” potentially redefining the standard of care for the disease. The ENGOT-OV16/NOVA trial was a Phase 3 double-blind, randomized, placebo-controlled international study of maintenance treatment with niraparib compared with placebo. Niraparib successfully achieved the primary endpoint of prolonging progression-free survival versus placebo in all three prospectively defined primary efficacy populations:
Author Interviews, Cancer Research, ESMO, Immunotherapy / 13.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28855" align="alignleft" width="130"]Dr. Mathew Galsky MD Associate Professor, Medicine, Hematology and Medical Oncology Assistant Professor, Urology Director, Genitourinary Medical Oncology The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai Dr. Mathew Galesky[/caption] Dr. Mathew Galsky MD Associate Professor, Medicine, Hematology and Medical Oncology Assistant Professor, Urology Director, Genitourinary Medical Oncology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since the development of combination cisplatin-based chemotherapy for the treatment of metastatic bladder (urothelial) cancer several decades ago, there have been few advances in the treatment of this disease. Further, until recently, there had been no global standard treatment options for patients with metastatic urothelial cancer progressing despite platinum-based chemotherapy. Several lines of evidence suggest that urothelial cancer may be sensitive to immunotherapeutic treatment strategies. Recently, in a phase I/II study published by Sharma and colleagues in Lancet Oncology, the anti-PD-1 antibody Nivolumab demonstrated a durable objective response rate of 24% in patients with metastatic urothelial cancer progressing despite platinum-based chemotherapy. To confirm to antitumor effects of Nivolumab in this patient population, we conducted a large global multicenter single-arm phase II study
Author Interviews, Cancer Research, Immunotherapy / 11.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28818" align="alignleft" width="200"]Bernard Vanhove, Chief Operating Officer Director of R&D and International Scientific Collaborations Ose Immunotherapeutics Bernard Vanhove[/caption] Bernard Vanhove, Chief Operating Officer Director of R&D and International Scientific Collaborations Ose Immunotherapeutics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Myeloid suppressive cells, including tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), represent an abundant immune cell type in the microenvironment of solid tumors where they promote tumor growth, metastases, angiogenesis, inhibiting anti-tumor immune responses. Myeloid cells selectively express SIRPα, an immune tyrosine associated inhibitory receptor (also named CD172a), which controls myeloid functions. We investigated the role of Effi-DEM, new generation checkpoint inhibitor specifically targeting the SIRP- α receptor on the strategic SIRP-α/CD47 pathway in human macrophages polarization and MDSC differentiation. CD47 the ligand of SIRP alpha is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells with a poor prognosis established. Effi-DEM is a selective antagonist of these myeloid suppressive cells as its target SIRP-α is expressed on these cells. Based on this rationale, the preclinical studies conducted with Effi-DEM have demonstrated its potential to transform suppressor myeloid and tumor associated macrophage cells in non-suppressive cells, thereby inducing a reactivation of the immune response. Effi-DEM has also shown to be effective in various aggressive cancer models with encouraging preclinical results, both in monotherapy and in therapeutic combinations with anti-PD-L1 (checkpoint inhibitors) and anti-CD137 (4-1BB) mAbs, activators of the T-cell response. Significant efficacy and survival increase data were demonstrated in models of hepatocarcinoma, melanoma and triple negative breast cancer.
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 10.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28705" align="alignleft" width="170"]Gabriel N. Hortobagyi, MD, FACP, F.A.S.C.O. Professor of Medicine Nellie B. Connally Chair in Breast Cancer Department of Breast Oncology Co-Director, Multidisciplinary Breast Cancer Research Program University of Texas MD Anderson Cancer Center Houston, Texas Prof. Gabriel N. Hortobagyi[/caption] Gabriel N. Hortobagyi, MD, FACP, F.A.S.C.O. Professor of Medicine Nellie B. Connally Chair in Breast Cancer Department of Breast Oncology Co-Director, Multidisciplinary Breast Cancer Research Program University of Texas MD Anderson Cancer Center Houston, Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: MONALEESA-2 is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer. The primary efficacy results from the pivotal MONALEESA-2 study show LEE011 (ribociclib) plus letrozole significantly extended progression-free survival (PFS) compared to a standard of care, letrozole, as a first-line treatment in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (HR= 0.556; 95% CI: 0.429-0.720; p=0.00000329)1. The results demonstrate that LEE011 plus letrozole reduced the risk of death or progression by 44% over letrozole alone, significantly extending PFS across all patient subgroups. More than half of women with measurable disease taking LEE011 plus letrozole saw their tumor size shrink by at least 30% during treatment (overall response rate (ORR) in patients with measurable disease = 53% vs 37%, p=0.00028)1.
Author Interviews, Chemotherapy, Immunotherapy, Lung Cancer / 13.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27869" align="alignleft" width="95"]Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital Dr. Chih-Hsin Yang[/caption] Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy. A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).