Ludwig Cancer Research and the Cancer Research Institute (CRI) have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer. The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center. […]Read more...
Ludwig Cancer Research and the Cancer Research Institute (CRI) have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer. The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center. The study is being conducted through the CVC Trials Network, which is jointly managed by Ludwig and CRI, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, and the biopharmaceutical company VentiRx Pharmaceuticals Inc.
“Ludwig has long supported the design and evaluation of new therapeutic strategies to improve the treatment options available to cancer patients,” said Jonathan Skipper, Ludwig’s executive vice president of Technology Development. “Employing immunotherapies in combination holds great promise in that endeavor. We are proud to be a part of this effort to bring investigational drugs being developed by different commercial partners to a single clinical trial and improve the standard of care for recurrent ovarian cancer, a disease for which patients today have few treatment options.”
The open-label trial is evaluating the combination of MedImmune’s investigational antibody cancer drug durvalumab, a PD-L1 inhibitor, and VentiRx’s investigational TLR8 agonist motolimod added to chemotherapy in locally advanced or recurrent ovarian cancers that have become resistant to platinum chemotherapy. Both of the investigational drugs have been found in other studies to have acceptable safety profiles when used alone.
The researchers expect that motolimod’s activation of TLR8 will create conditions within tumors that are optimal to enhancing the effects of durvalumab. Further, when given with chemotherapy, motolimod could boost immune responses against cancer cells that are not engaged by durvalumab by helping the immune system “see” cancer antigens. Since the two immunotherapies work in distinct ways, they could have additive effects, inducing more potent and durable anti-tumor immune responses.
“This study is a good example of what’s possible when researchers have access to new therapies and are permitted to test hypotheses supported by the most recent science,” said Ludwig Lausanne director George Coukos. “We are hopeful that the combined therapies we are testing in this trial will be of great benefit to ovarian cancer and other cancer patients.”
Patients enrolled in the trial will be treated with the chemotherapeutic drug pegylated liposomal doxorubicin (PLD), which is the current standard of care for ovarian cancer after the failure of platinum therapy. They will also receive durvalumab and motolimod, with the Phase 1 and 2 portions of the trial running successively. The primary objective of the Phase 1 cohort of the study is to evaluate the safety and optimal dosage of the combination. The Phase 2 cohort of the trial will measure the efficacy of the treatment by evaluating the number of patients whose tumors have not progressed at six months.
Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 expression enables tumours to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient’s immune system and attack the cancer. Durvalumab is being investigated in an extensive clinical trial program, as monotherapy or in combination with tremelimumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers.
Motolimod binds and activates Toll-like receptor 8 (TLR8), which is found in a variety of immune cells and serves as a key initiator of the innate immune response. Notably, it is expressed by myeloid dendritic cells, which help direct and boost T cell responses against infectious agents and cancers. Motolimod has been shown to be safe when combined with PLD in a previous study on ovarian cancer, with evidence of clinical benefit. The motolimod-PLD combination is currently under evaluation in a large, randomized, placebo-controlled phase 2 clinical study in patients with ovarian cancer.
“This clinical trial is part of a larger clinical research program supported by Ludwig and CRI to speed the evaluation of novel cancer immunotherapies, alone or in combination with other cancer drugs,” said Adam Kolom, managing director of CRI’s Clinical Accelerator, which funds the trials. “All of the studies have, as additional objectives, the collection of genetic and immunologic data derived from clinical samples that are obtained from patients. Such information will provide clues to the impact of the evaluated therapies and suggest refined or new strategies for treating cancer.”
Washington, D.C.—A team of scientists led by Carnegie’s Jacqueline Faherty has discovered the first evidence of water ice clouds on an object outside of our own Solar System. Water ice clouds exist on our own gas giant planets–Jupiter, Saturn, Uranus, and Neptune–but have not been seen outside of the planets orbiting our Sun until now. […]Read more...
Washington, D.C.—A team of scientists led by Carnegie’s Jacqueline Faherty has discovered the first evidence of water ice clouds on an object outside of our own Solar System. Water ice clouds exist on our own gas giant planets–Jupiter, Saturn, Uranus, and Neptune–but have not been seen outside of the planets orbiting our Sun until now. Their findings are published by The Astrophysical Journal Letters. At the Las Campanas Observatory in Chile, Faherty, along with a team including Carnegie’s Andrew Monson, used the FourStar near infrared camera to detect the coldest brown dwarf ever characterized. Their findings are the result of 151 images taken over three nights and combined. The object, named WISE J085510.83-071442.5, or W0855, was first seen by NASA’s Wide-Field Infrared Explorer mission and published earlier this year. But it was not known if it could be detected by Earth-based facilities.
“This was a battle at the telescope to get the detection,” said Faherty.
Chris Tinney, an Astronomer at the Australian Centre for Astrobiology, UNSW Australia and co-author on the result stated: “This is a great result. This object is so faint and it’s exciting to be the first people to detect it with a telescope on the ground.”
Brown dwarfs aren’t quite very small stars, but they aren’t quite giant planets either. They are too small to sustain the hydrogen fusion process that fuels stars. Their temperatures can range from nearly as hot as a star to as cool as a planet, and their masses also range between star-like and giant planet-like. They are of particular interest to scientists because they offer clues to star-formation processes. They also overlap with the temperatures of planets, but are much easier to study since they are commonly found in isolation.W0855 is the fourth-closest system to our own Sun, practically a next-door neighbor in astronomical distances. A comparison of the team’s near-infrared images of W0855 with models for predicting the atmospheric content of brown dwarfs showed evidence of frozen clouds of sulfide and water. “Ice clouds are predicted to be very important in the atmospheres of planets beyond our Solar System, but they’ve never been observed outside of it before now,” Faherty said. The paper’s other co-author is Andrew Skemer of the University of Arizona.