gemcitabine elaidate (CO 1.01) / Clovis, Karo Pharma - LARVOL DELTA

Gemcitabine elaidate and ONC201 combination therapy for inhibiting pancreatic cancer in a KRAS mutated syngeneic mouse model. (PubMed, Cell Death Discov) - "Simultaneous inhibition of the PI3K/AKT and MEK pathways with ONC201 is an attractive approach to potentiate the effect of GEM. Our findings provide insight into rational-directed precision chemo and immunotherapy therapy in PDAC."

Combination therapy • IO biomarker • Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • PDX1 • TNFRSF10B

Transforming Cancer-Associated Fibroblast Barrier into Drug Depots to Boost Chemo-Immunotherapy in "Shooting Fish in a Barrel" Pattern. (PubMed, ACS Nano) - "By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier."

Journal • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • IL12A

Palmitoyl Carnitine-Anchored Nanoliposomes for Neovasculature-Specific Delivery of Gemcitabine Elaidate to Treat Pancreatic Cancer. (PubMed, Cancers (Basel)) - "Our results demonstrate higher cellular uptake, inhibition in migration, as well as angiogenesis potential and significant apoptosis induced by PGPLs in 3D multicellular tumor spheroids of pancreatic cancer cells. Hence, PGPLs could be an effective and novel nanoformulation for the neovasculature-specific delivery of Gemcitabine Elaidate to treat PDAC."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy. (PubMed, Nanomedicine) - "Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Wirelessly Activated Nanotherapeutics for In Vivo Programmable Photodynamic-Chemotherapy of Orthotopic Bladder Cancer. (PubMed, Adv Sci (Weinh)) - "The device successfully delivers four weekly light doses to the bladder while the nanocarrier promoted the specific accumulation of drugs in tumors. This approach facilitates the combination of low-irradiance PDT (1 mW cm ) and low-dose chemotherapy (≈1500× lower than clinical dose) which significantly cures and controls orthotopic disease burden (90% treated vs control, 35%) in mice, demonstrating a potential new bladder cancer treatment option."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Phase I, Prospective, Open-Labeled Study to Evaluate the Safety and Immunogenicity of MVC-COV1901 (clinicaltrials.gov) - P1; N=45; Not yet recruiting; Sponsor: Medigen Vaccine Biologics Corp.

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Tivantinib-gemcitabine: Pharmacological rational for a new combination in pancreatic cancer (ESMO 2014) - Presentation time: 27.09.2014, 12:45 - 13:45; Abstract #474P; "Cells and tissues showed a variable expression of c-Met, and cells with the highest c-Met levels were more sensitive to tivantinib and tivantinib-gemcitabine combination. Median drug-effect analysis revealed strong synergistic interaction. However this synergism was not associated to the increase in the accumulation of gemcitabine-nucleotides, as observed for crizotinib-gemcitabine."

Preclinical • Oncology • Pancreatic Cancer

Study to Evaluate Efficacy of CO-1.01 as Second Line Therapy for Gemcitabine-Refractory Stage IV Pancreatic Adenocarcinoma (clinicaltrials.gov) - P2; N=19; Completed; Sponsor: Clovis Oncology, Inc.; N=35 -> 19

Enrollment change • Biosimilar • Oncology • Pancreatic Cancer

Chemotherapeutic Strategies for Peritoneal Dissemination of Gastric Cancer (PubMed) - Gan To Kagaku Ryoho - "...For those who have such complications, treatment via chemotherapy including S-1, capecitabine, or cisplatin is inappropriate. Therefore, methotrexate plus 5-fluorouracil(5-FU), 5-FU continuous infusion, 5- FU plus l-levofolinate, or paclitaxel are generally administered to such patients. To improve the efficacy of chemotherapy for such patients, an ongoing clinical trial(JCOG1108)is comparing triplet chemotherapy(FLTAX)including 5-FU plus l-levofolinate plus paclitaxel with chemotherapy including 5-FU plus l-levofolinate...Longer survival was observed in the IP paclitaxel group compared with the other groups; however, this difference did not reach statistical significance. We hope that the evaluation of data from clinical trials would result in the identification of the optimal treatment strategy for patients with gastric cancer with peritoneal dissemination."

Journal • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

Phase IB trial of cisplatin (C), gemcitabine (G), and veliparib (V) in patients with known or potential BRCA or PALB2-mutated pancreas adenocarcinoma (PC) (ASCO 2014) - Presentation time: Sunday, Jun 1; 8:00 AM - 11:00 AM; Abstract #4023; P1b, N=17; NCT01585805; "The RP2D of veliparib is 80 mg PO BID day 1-12 q 3 weeks with fixed dose C + G. Main grade 3-4 toxicities are hematologic, fatigue. The combination of C, G + V shows high activity in BRCA mut PC. A randomized phase II trial evaluating C, G +/- V is underway in BRCA/PALB2 mut PC..."

P1 data • Oncology • Pancreatic Cancer

Q2 '11 Presentation (Clavis Pharma) - CP-4126(CO-101) / Clavis; Anticipated enrollment completion of LEAP study, pivotal study in pancreatic cancer in Q1 2012; Anticipated top line data of LEAP study, pivotal study in pancreatic cancer by end of 2012; Anticipated hENT1 biomarker study data in Q4 2011; Anticipated stage two decision of P2 study for second-line refractory pancreatic cancer in Q4 2011; Anticipated final data of P2 study for second-line refractory pancreatic cancer by year end 2012

Anticipated biomarker data • Anticipated enrollment completion • Anticipated P2 trial final data • Anticipated top-line data • None • Oncology • Pancreatic Cancer

End-tidal carbon dioxide variation after a 100- and a 500-ml fluid challenge to assess fluid responsiveness. (PubMed) - Ann Intensive Care - "During surgery, when alveolar ventilation and CO2 production are constant, ΔEtCO2500 is fairly reliable to assess FR. When the variation of EtCO2 is >5.8 %, all patients were responders, but no conclusion could be done when this variation was <5.8 %. ΔEtCO2100 failed to predict FR. Trial registration CPP Lyon Sud Est III ref: 2013-027 B, Number ID RCB: 2013-A00729-36 delivered by the ANSM)."

Journal • Biosimilar • Complement-mediated Rare Disorders

Q1 '12 Results (Clavis Pharma) - CO-101 / Clavis; Anticipated top-line data from P2 LEAP study in 1st line metastatic pancreatic cancer in Q4 2012; Anticipated European co-promotion decision in 2013; Anticipated NDA filing in 2013; Anticipated MAA filing in 2013

Anticipated MAA filing • Anticipated NDA filing • Anticipated P2 data • Anticipated partnership deal • Pancreatic Cancer

A study of CP-4126 in patients with advanced pancreatic cancer (clinicaltrials.gov) - P2, N=40 -> 21; Active, not recruiting -> Completed; Completion date: Mar 2011 -> Sep 2011

Trial completion • Pancreatic Cancer

Personality Dark Triad: Portuguese Validation of the Dirty Dozen (EPA 2017) - " A community sample composed of 286 university students (69.2% females; mean age=21.09±2.133; range: 17-33) answered the Portuguese preliminary versions of the Dirty Dozen and of the Altruism dimension from HEXACO-100 (Ashton & Lee, 2009). The Portuguese version of Dirty Dozen has good reliability and validity. It could be very useful both in clinical and research contexts, namely in an ongoing project on the relationship between dark triad and perfectionism traits."

Clinical • Biosimilar • CNS Disorders

Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204). (PubMed) - Dig Surg - "Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC."

Journal • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

First quarter report 2010 (Clavis Pharma) - Clovis Oncology agreement w/ Ventana Medical to develop companion diagnostic for hENT1 in pancreatic cancer, positive pilot P2 data, new randomized P2 to start in May in pancreatic cancer, data expected 1H ‘12, focus on intravenous use & halt development of oral formulation, no safety issues from P1, granted Orphan Drug Designation for TX  by FDA & EC, high interest expressed by potential partners in Japan & Asia Pacific

Clinical trial news • Regulatory update

Synthesis of Two-Dimensional CoS1.097/Nitrogen-doped Carbon Nanocomposites Using Metal-Organic Framework Nanosheets as Precursors for Supercapacitor Application. (PubMed) - J Am Chem Soc - "Moreover, the composite electrode also shows high rate capability. Its specific capacitance delivered at current density of 30.0 A g-1 retains 56.8% of the value at 1.5 A g-1."

Journal • Biosimilar

Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies. (PubMed, Clin Transl Oncol) - P2, P3; "Statin use seems to be associated with better overall survival among patients with metastatic pancreatic cancer treated with first-line chemotherapy. Prospective studies designed specifically to assess this potential effect of statins are needed."

Journal • P3 data • Retrospective data