Author Interviews, Immunotherapy, Lancet, Lung Cancer / 23.12.2016 Interview with: Dr Kiyotaka Yoh Department of Thoracic Oncology National Cancer Center Hospital East Kashiwa, Japan 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. (more…)
Author Interviews, Breast Cancer, Immunotherapy / 22.12.2016 Interview with: Joyce O'Shaughnessy, MD Co-Chair, Breast Cancer Research Texas Oncology-Baylor Charles A. Sammons Cancer Center 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%). (more…)
Author Interviews, Boehringer Ingelheim, Cancer Research / 12.12.2016 Interview with: Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy What is the background for this study? What are the main findings? Response: LUME-Meso II is an international study designed to evaluate the safety and efficacy of nintedanib plus pemetrexed/cisplatin, followed by nintedanib versus placebo plus pemetrexed/cisplatin, followed by placebo, for the treatment of patients with unresectable malignant pleural mesothelioma (MPM). MPM is a rare cancer that affects the cells that make up the mesothelium of the pleura – the lining or membrane that covers and protects the lungs. It represents less than 1% of all cancers and is often related to long-term asbestos exposure with some suffering from malignant mesothelioma. A significant improvement in progression-free survival (PFS), the study’s primary endpoint, was observed for patients receiving nintedanib plus chemotherapy compared to patients receiving placebo plus chemotherapy. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016 Interview with: Vince Giranda, M.D., PH.D. Project Director AbbVie Oncology Development 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. (more…)
Author Interviews, Dermatology, Immunotherapy, Rheumatology / 28.11.2016 Interview with: Atul Deodhar, M.D., M.R.C.P. Rheumatology Oregon Health and Science University 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. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis / 22.11.2016 Interview with Ralph Kern, M.D. Senior vice president, Worldwide Medical Biogen 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. (more…)
Author Interviews, Cancer Research, Immunotherapy / 17.11.2016

MEDICALRESEARCH.COM INTERVIEW WITH: THOMAS W. DUBENSKY, JR., PH.D. CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. 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 Interview with: Timothy Beukelman, MD, MSCE Associate Professor of Pediatrics Division of Rheumatology and Division of Clinical Immunology & Rheumatology University of Alabama at Birmingham 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. (more…)
Author Interviews, Immunotherapy, JAMA, Melanoma / 15.11.2016 Interview with: Feng Xie, Ph.D. Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences McMaster University 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. (more…)
Author Interviews, Cancer Research, Immunotherapy / 11.11.2016 Interview with: Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 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. (more…)
Author Interviews, Cancer Research, Immunotherapy, Vaccine Studies / 09.11.2016 Interview with: Leslie Chong Imugene Chief Operating Officer Armadale, Australia Leslie Chong Imugene Chief Operating Officer Armadale, Australia 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. (more…)
Author Interviews, ESMO, Immunotherapy, Lung Cancer / 21.10.2016 Interview with: Shirish Gadgeel, MD Leader of the Thoracic Oncology Multidisciplinary team Professor at Karmanos Cancer Institute Detroit 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. (more…)
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 17.10.2016 Interview with: 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 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. (more…)
Author Interviews, Cancer Research, ESMO, Immunotherapy, NYU / 16.10.2016 Interview with: Arjun Balar, M.D. Assistant Professor of Medicine Director - Genitourinary Medical Oncology Program NYU Perlmutter Cancer Center New York, NY 10016 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. (more…)
Author Interviews, ESMO, Immunotherapy, Ovarian Cancer / 14.10.2016 Interview with: 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 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: (more…)
Author Interviews, Cancer Research, Immunotherapy / 11.10.2016 Interview with: Bernard Vanhove, Chief Operating Officer Director of R&D and International Scientific Collaborations Ose Immunotherapeutics 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. (more…)
Author Interviews, Dermatology / 11.10.2016 Interview with: Dr. Kristian Reich Professor of Dermatology at the Georg-August-University Göttingen and inflammation specialist Dermatologikum Hamburg in Germany What is the background for this study? What are the main findings? Response: While there is ongoing research into the causes and triggers of psoriasis, recent studies have identified IL-23 as a main driver of the IL-23/IL-17 pathway which is now thought to be the predominant pathway in the psoriasis inflammatory cascade. Selective Inhibition of IL-23 may present a new targeted strategy for treating patients with the condition. The hope for molecules selectively targeting IL-23, specifically the p19 component of the cytokine, is that newer therapies, like tildrakizumab, can more selectively control the disease allowing more patients to achieve higher and even more durable clinical responses. The two pivotal Phase-3 studies (reSURFACE 1 and 2) evaluated the efficacy and safety of the IL-23 inhibitor tildrakizumab in adult patients with moderate-to-severe plaque psoriasis, and results through week 28 were presented for the first time as part of the Late Breaking News Session at EADV. In the reSURFACE 1 and 2 pivotal Phase-3 studies, tildrakizumab, a selective IL-23p19 inhibitor, was evaluated against placebo and etanercept to assess efficacy, safety and tolerability. The co-primary efficacy endpoint of the two placebo-controlled studies was a) the proportion of patients with Psoriasis Area Sensitivity Index 75 (PASI 75) response at week 12 compared to placebo and the proportion of participants with a Physician’s Global Assessment (PGA) score of clear or minimal with at least a 2 grade reduction from baseline at week 12 compared to placebo. The reSURFACE 2 also included an etanercept comparator arm, with a key secondary endpoint comparing tildrakizumab and etanercept on PASI 75 and PGA. Other co-secondary endpoints of both placebo controlled studies included PASI 90 and PASI 100 responses at week 12 and PASI 75, 90 and 100 and PGA responses from baseline at Week 28. (more…)
Author Interviews, Breast Cancer, ESMO, Immunotherapy / 10.10.2016 Interview with: 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 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. (more…)
Alzheimer's - Dementia, Author Interviews, Immunotherapy, Nature / 01.09.2016 Interview with: Roger M. Nitsch, MD Professor and Director Institute for Regenerative Medicine · IREM University of Zurich Campus Schlieren Switzerland What is the background for this study? What are the main findings? Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease.  The removal of amyloid from patients brains were both dose- and time-dependent.  We also observed initial hints for stabilized brain functions in patients receiving aducanumab.  In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease. The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously.  In one third of the ARIA cases, patients experienced transient headaches.  None of the patients had to hospitalized because of ARIA. (more…)
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016 Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons. (more…)
Author Interviews, Cancer Research, Immunotherapy / 26.08.2016 Interview with: Dr Charles Akle, Chairman and Linda Summerton, CEO Immodulon Therapeutics Short Hills, NJ 07078 and London, UKDr Charles Akle, Chairman and Dr. Linda Summerton, CEO Immodulon Therapeutics Short Hills, NJ 07078 and London, UK What is the background for Immodulon? Would you tell us a little about Dr. Charles Akle? Response: Immodulon was established in November 2007. The founder and Chairman, Dr Charles Akle, was a Harley Street surgeon and pioneer of keyhole surgery who established Immodulon with the financial support of a former patient. His interest in immunology led him to the potential of cancer immunotherapy long before the term “immuno-oncology” was coined and when skepticism, rather than optimism was the norm. His ambition from the start was to develop an affordable immunotherapy treatment that would transform the way that cancer is treated in the world today. Since then, Immodulon has become a leading, independent biopharmaceutical company with one of the longest running research projects into how to harness the power of the immune system in treating cancer. It also has its own R&D and manufacturing capability in Lyon, France. The wider Immodulon senior team has extensive experience of bringing drugs to market and includes Dr James Shannon and Dr Jean Pierre Bizzari. (more…)
Author Interviews, Immunotherapy, Lymphoma, Pharmacology / 14.08.2016 Interview with: Dirk Huebner, MD Senior Medical Director Oncology Therapeutic Area Unit Takeda Pharmaceutical Company What is the background for this study? What are the main findings? Response: Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. Cutaneous T-cell lymphoma, also known as CTCL, is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. ADCETRIS® (brentuximab vedotin) is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50 percent of patients with CTCL. The Phase 3 ALCANZA trial compared the use of single-agent ADCETRIS to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy. The study met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm. (more…)
Author Interviews, Immunotherapy, Leukemia, Stem Cells, Transplantation / 12.08.2016 Interview with: Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 What is the background for this study? What is goal of this Study? Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017. The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation . (more…)
Author Interviews, Immunotherapy, Pulmonary Disease / 20.07.2016 Interview with: Ganesh Raghu, M.D. FACP, FCCP Professor of Medicine Division of Pulmonary and Critical Care Medicine and Director of Center for Interstitial Lung Diseases Director, Interstitial Lung Disease/Sarcoid/Pulmonary Fibrosis Program University of Washington Medical Center Seattle, Washington What is the background for this study? Response: This is a new post-hoc analysis of the Phase III INPULSIS trials, including a total of 1,061 patients with idiopathic pulmonary fibrosis (IPF), which has been published in the American Journal of Respiratory and Critical Care Medicine. As background, achieving an accurate diagnosis of IPF in clinical practice is very complex and challenging. Physicians use an imaging technique called high resolution computed tomography (HRCT) to help them identify the presence of scarring (fibrosis) and, specifically, the presence of usual interstitial pneumonia (UIP) pattern in the lungs. The radiological changes called "honeycombing" are the key feature of the UIP pattern visible on HRCT and the pattern of UIP is the hallmark of the fibrosis in patients with IPF. In the absence of definitive UIP pattern on HRCT images of the lungs, the diagnosis of  idiopathic pulmonary fibrosis requires the microscopic features of UIP in the surgical lung biopsy (SLB) based on current guidelines for diagnosis of IPF. However, it can be challenging to confirm that scarring in the absence of honeycombing on HRCT meets the strict guideline criteria for a definitive diagnosis of IPF. For a large group of patients who do not receive a confirmed diagnosis of IPF according to guidelines, including those not eligible for surgical lung biopsy, the clinical course of their condition and the effectiveness of  idiopathic pulmonary fibrosis treatment remains unknown. Therefore, investigations into the behavior of the disease across diagnostic subgroups are important. (more…)
Author Interviews, Immunotherapy, Prostate Cancer / 16.07.2016 Interview with: Julie Graff, M.D. Oncologist specializing in prostate cancer Knight Cancer Institute Oregon Health & Science University What is the background for this study? What are the main findings? Response: Men with metastatic prostate cancer that is not responding to second-line androgen receptor blockade (such as enzalutamide) have a very limited life expectancy. We found that adding immunotherapy to enzalutamide in men whose prostate cancer is no longer responding to enzalutamide could exert a very strong anti-cancer effect. Previous experience with this type of immunotherapy in prostate cancer patients suggested this type immunotherapy does not work in patients with prostate cancer. What we have found will lead to more studies of this agent. (more…)
Author Interviews, BMJ, Immunotherapy, Johns Hopkins, Rheumatology / 27.06.2016 Interview with: Laura C. Cappelli, M.D Johns Hopkins University School of Medicine What is the background for this study? What are the main findings? Response: We had been referred several patients with inflammatory arthritis or dry mouth and dry eyes after being treated with immune checkpoint inhibitors. When searching the literature for information on how to evaluate and treat these patients, we realized that there was minimal information available. We wanted to describe our experience and inform the medical community about these events so that recognition could increase. (more…)
Author Interviews, Cancer Research, Chemotherapy, Immunotherapy / 15.06.2016 Interview with: Professor Frances Balkwill OBE, FMedSci Lead, Centre for Cancer and Inflammation Barts Cancer Institute Queen Mary University of London London What is the background for this study? Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors. We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation. (more…)
ASCO, Author Interviews, Cancer Research, Immunotherapy / 08.06.2016 Interview with: Dr. Arjun Balar MD Assistant Professor, Department of Medicine Co-Leader Genitourinary Cancers Program NYU Langone Medical Center Laura and Isaac Perlmutter Cancer Center What is the background for this study? Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to 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. Atezolizumab is a PD-L1 blocking antibody that reactivates the body¹s immune system to fight bladder cancer and has been recently FDA approved in the management of advanced urothelial cancer in the second-line setting after failure of platinum-based chemotherapy. (more…)
ASCO, Author Interviews, Cancer Research, Immunotherapy, University of Pittsburgh / 07.06.2016 Interview with: Robert L. Ferris, M.D., Ph.D. Robert L. Ferris, M.D., Ph.D. UPMC Endowed Professor and Vice-Chair Associate Director for Translational Research Co-Leader, Cancer Immunology Program What is the background for this study? What are the main findings? Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<> (UPCI) co-led CheckMate-141<> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed. Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group. Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug. (more…)