Oncology Highlights - June 2016
Reading our newsletter will only take a few minutes and allows you to keep up to date with last month’s news items on oncology drug development.
Kind regards, the SMS-oncology team
Simple aspirin as cancer treatment option?
Researchers at the Center for Molecular Medicine in Norway found that the use of aspirin by colorectal cancer (CRC) patients was significantly associated with both CRC-specific survival (CSS) and overall survival (OS). Patients who took aspirin had a 9 times higher chance to survive both the studies’ seven-year time frame and in general, suggesting aspirin as a possible second-line CRC therapy. The mechanisms that drive aspirin-induced survival are not yet fully understood by the researchers. In this observational, retrospective study the team looked at the database of the Cancer Registry of Norway as well as a second nation-wide medical registry, the Norwegian Prescription Database, to identify 23,162 patients diagnosed with CRC between 2004 and 2011, of which 26,3% had a prescription for aspirin. The results published in the Journal of Clinical Oncology indicates aspirin as an inexpensive, widely-available cancer treatment option, especially considering that most chemotherapy drugs cost thousands of dollars a year. Read more >
One-third more malignant ovarian cancer lesions resected by novel fluorescent agent guided surgery
A recent study published in the American Association for Cancer Research (AACR)’s journal Clinical Cancer Research, shows the added value of an innovative tumor-specific fluorescent agent in guided surgery to remove additional tumors. The completeness of surgical tumour removal is a key factor in determining survival of patients with solid tumors. However, complete removal of all tumor tissue during surgery may be problematic as surgical oncologists often reply only on visual inspection and/or physical examination (palpation). A gynecological surgical team from the Leiden University Medical Center (LUMC) has used a novel targeted Near Infra-Red (NIR)-based approach to detect “invisible” tumor cells. Even though not visible to the human eye, NIR fluorescence can penetrate a few centimeters into tissues thus allowing real time detection of targets underneath the surface. The imaging agent used, OTL38, comprises of a folate analogue conjugated to a NIR fluorescent dye and as such binds to the folate receptor; a receptor expressed in over 90% of epithelial ovarian cancers. Using OTL38 to image ovarian cancers during surgery, the team was able to resect an additional 29% of malignant lesions that were not identified previously with visual inspection and/ or palpation. Read more >
Biomarker strategy for patient selection improves efficacy outcomes
With an increasing trend towards precision or personalized medicine, patients are often selected to receive an investigational therapy based on a specific gene mutation, protein or genomic biomarker as they’re regarded to benefit (most) from the particular treatment. But does using a biomarker for patient selection improve efficacy outcomes? With this question in mind, a large meta-analysis on 346 published phase I trials including 13,203 patients was performed and presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. In the phase I studies a personalized biomarker-based selection strategy was found to be an independent predictor of improved response rates (median, 30.6% vs 4.9%) and progression-free survival (PFS, median, 5.7 vs 2.95 months). Targeted arms without biomarker use had median response rates comparable with cytotoxic agent arms. Response rates were especially higher when genomic biomarkers versus protein biomarkers were used. The current study seems to be the first to demonstrate that these benefits are apparent even at an early stage of clinical development, suggesting that validly proven tumor biomarkers should be increasingly used to select patients for phase I clinical trials. Read more >
Cancer prediction based on your internet searches?
Detecting cancer as early as possible is critical for all types of diseases and new methods of predicting cancer development are paramount. But imagine if, based on your internet search history, you could receive a diagnosis and information on how to get treatment? Microsoft scientists recently explained this to be a possible scenario. Even before patients were diagnosed with cancer by a physician, the scientists were in some cases able to identify internet users who were suffering from pancreatic cancer only by evaluating their search engine queries. The full web search histories of 9.2 million Bing users were investigated in order to differentiate between experiential diagnostic queries and more general exploratory queries. The aim was to assess whether going backwards and examining previous queries would show that the searchers were experiencing symptoms before diagnosis, and ultimately use this approach to predict development of the disease. Microsoft’s researchers reported that 5 -15% of pancreatic cancer cases could be predicted, with false positive rates of as low as one in 100,000, hoping their work could lead to early detection of cancer in the future. This exiting method brings both enthusiasm and questions about what the use of online data means for the future of medical diagnoses. The study is published in the Journal of Oncology Practice of the American Society of Clinical Oncology (ASCO). Read more >
“Emerging Star of the Year Award” to mRNA immuno-oncology biotech
BioNTech AG has won the "Emerging Star of the Year Award" at the European Mediscience Awards 2016 in London. The award is given to young lifescience companies that show to have substantial market impact with their innovation or technologies. BioNTech’s novel technologies focus on mRNA cancer immunotherapy and the privately held company develops personalized potent mRNA based medicines such as Chimeric Antigen Receptors (CAR)/T cell Receptor (TCR)-based products and novel antibody checkpoint immunomodulators for cancer treatment. The decisive factors for being award included the signing of four collaborations with international well known pharmaceutical companies to further advance their immuno-oncology pipeline, in addition to having four products in the clinic, two more that are predicted to enter this year, and the launch of their first molecular cancer diagnostic test. In accordance with this award, the novelty of BioNTechs’ approach has been accredited by Nature with 2 published articles, including the recent article “Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy”. The results of this study show a clinically applicable and systemic nanoparticle mRNA vaccine (RNA-LPX) with body wide effects in targeting dendritic cells and eliciting a strong immune response, involving both the adaptive (T cell-mediated) and innate (type-I interferon (IFN)-mediated) immune system. Read more (Nature)>, Read more (Award)>
Much sooner than expected: first clinical trial with CRISPR gene editing technology
The most popular approaches for targeted genome editing is currently theClustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technique, while Cas9 stands for CRISPR-associated and is the name of the endonuclease9 used in this method. The CRISPR system is used to implement double-stranded DNA breaks (DSB) in a sequence specific manner in order to facilitate genome editing in DNA sequences wherever needed. The first practice of the CRISPR technology in human clinical trials was thought to be in 2017. Surprisingly, the National Institute for Health (NIH) Recombinant DNA Advisory Committee (RAC) recently unanimously approved a clinical trial protocol by the University of Pennsylvania involving the first-in-human use of gene editing via CRISPR/Cas9 technology. Here, CRISPR would be used to create genetically altered T cells expressing a chimeric antigen receptor (CAR) to be able to target three different kinds of cancers addressing the tumor associated antigens NY-ESO-1, and additionally edit PD-1 as well as the natural T cell receptor. The trial will recruit 15 patients and will be conducted at the MD Anderson Cancer Centre (Texas), the University of California (San Francisco) and the University of Pennsylvania. The latter will also manufacture the genetically modified T cells. Read more >
Strategies for a personalized cancer immunotherapies using mRNA approaches (Source: BioNTech)
EMA / FDA
EMA oncology drug recommendations for approval June 2016:
The Committee for Medicinal Products for Human Use (CHMP) adopted a position opinion for:
- Zalmoxis (allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2), MolMed SpA). Zalmoxis is indicated as adjunctive treatment in hematopoietic stem cell transplantation (HSCT) of adult patients with haematological malignancies. The advanced therapy medicinal product (ATMP) received orphan drug designation in 2003.
- Keytruda (pembrolizumab, Merck Sharp & Dohme Limited) indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received approved therapy for these mutations prior to receiving Keytruda.The humanized antibody is already approved for melanoma.
- Cervarix (human papillomavirus vaccine [types 16, 18], GlaxoSmithKline Biologicals),a vaccine used as preventive care against certain types of cancer caused by Human Papillomavirus (HPV) type 16 or 18, that now extended its indication for the prevention of ano-genital lesions and anal cancers, in addition to the already approved use for prevention of cervical, vulvar, and vaginal genital lesions and cervical cancer. Cervarix can be used from the age of 9 years.
- Cobas EGFR Mutation Test v2 (US-IVD, Roche Molecular Systems)using plasma specimens as a companion diagnostic test for the detection of exon 19 deletions or exon 21 (L858R) substitution mutations in the epidermal growth factor receptor (EGFR) gene to identify patients with metastatic non-small cell lung cancer (NSCLC) eligible for treatment with Tarceva (erlotinib). NSCLC accounts for about 85% of all lung cancers and the kind of treatment depends on the type of mutation within EGFR.
FDA simplifies guidelines on Compassionate Use Program
The FDA released this month the final and improved Individual Patient Expanded Access Investigational New Drug Application (Form FDA 3926), a form that can be used by physicians for requesting “expanded access" for individual patient. An expanded access program (EAP), or also referred to as compassionate use program (CUP), allow sponsors to broaden the access to their investigational new drug to individual patients with serious or life-threatening conditions who do not meet the enrollment criteria for the ongoing clinical trial, and for whom no equivalent drug alternative is available. The simplified form should now take only 45 minutes to be completed, thereby drastically reducing the amount of time spent filling out a request. In addition, the FDA released a separate guidance either for a question and answer format that explains what expand access is, and a second guidance on how to charge patients for investigational drugs. Read more >