Ohio State-Developed Drug Receives FDA Approval for Treatment of Chronic Lymphocytic Leukemia and Small Cell Lymphoma
On Nov. 21, 2019, the U.S. Food and Drug Administration (FDA) approved the use of acalabrutinib for first-line therapy in chronic lymphocytic leukemia (CLL) and small cell lymphoma (SCL). This was the first full approval of the targeted drug therapy, which was developed and tested at the OSUCCC – James in collaboration with Acerta Pharma. Acalabrutinib is a second-generation Bruton tyrosine kinase (BTK) inhibitor, a newer class of drugs shown to improve the survival of patients with mantle cell lymphoma in addition to CLL and SCL. The foundational basic-science research, initial phase I clinical trial and numerous sequential phase II and III trials that led to FDA approval of acalabrutinib were performed by a team of researchers at the OSUCCC – James led by John C. Byrd, MD, Distinguished University Professor and co-leader of the Leukemia Research Program.
Acalabrutinib Shows Good Tolerability & Efficacy in CLL Patients Intolerant to Ibrutinib
Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who had to discontinue therapy with the drug ibrutinib because of adverse effects from treatment may benefit from a newer drug called acalabrutinib that showed promising results among patients in a multicenter clinical trial co-led by OSUCCC – James researchers. Published in the journal Blood Advances, the phase I/II study showed that acalabrutinb is tolerable and demonstrates clinical benefit for many patients with CLL who develop ibrutinib intolerance. Ibrutinib was the first drug designed to target the Bruton tyrosine kinase (BTK) protein that is essential to CLL cell survival and proliferation. This study was led by an Ohio State CLL team directed by Jennifer Woyach, MD, of the Leukemia Research Program.
Partial Breast Irradiation Effective, Convenient Treatment Option for Low-Risk Breast Cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early-stage breast cancer, according to new data from a national clinical trial involving researchers at the OSUCCC – James. This randomized phase III study compared whole breast irradiation with partial breast irradiation in a large group of women with stage 0, 1 or 2 breast cancer. More than 4,200 patients were enrolled in the study as part of an NRG Oncology cooperative group clinical trial. Julia White, MD, head of breast radiation oncology and member of the Translational Therapeutics Program at the OSUCCC – James, was co-principal investigator for the study.
Novel Anticancer Vaccine Shows Promise in Phase I Study
Promising results from an OSUCCC – James phase I clinical trial on a novel peptide vaccine suggest an important potential benefit of this vaccine and warrant its continuing development for treating patients with metastatic or recurrent solid tumors that overexpress the HER-2 protein. Led by principal investigator Pravin Kaumaya, PhD, a professor in the Department of Obstetrics and Gynecology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, the trial demonstrates that the vaccine, called B-Vaxx, is well tolerated and can generate sustained anti-HER-2 immune response compared to humanized monoclonal antibodies, to which most patients develop resistance. The present study shows preliminary indication that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies such as Herceptin® and Perjeta®.
Trial Analyses Suggest Only 2 of 3 Low-Grade Glioma Subgroups May Benefit From Adding PCV Chemotherapy to Radiotherapy
A recent updated predictive analysis of the three World Health Organization (WHO)-defined molecular glioma subgroups based on isocitrate dehydrogenase 1/2 (IDH) mutation status and 1p/19q co-deletion status represented in the high-risk low-grade glioma treatment arms of the NRG-RTOG 9802 clinical trial indicates that both IDH-mutant subgroups could benefit from the addition of PCV chemotherapy to radiotherapy treatment. This data, included in an abstract of which researchers at the OSUCCC – James were lead authors, was delivered during a Best of ASCO (American Society of Clinical Oncology) oral presentation at the ASCO Annual Meeting. Erica Bell, PhD, associate professor in the Department of Radiation Oncology at Ohio State, was first author. Department Chair Arnab Chakravarti, MD, was senior author. Both are in the OSUCCC – James Translational Therapeutics Program.
Findings Strengthen Link Between Vitamin E Acetate and Vaping-Associated Lung Injuries
Research reported in the New England Journal of Medicine by the Centers for Disease Control and Prevention (CDC) in collaboration with the OSUCCC – James strengthens prior findings on the link between vitamin E acetate and EVALI (E-cigarette or vaping product use-associated lung injury). In this study, the CDC analyzed bronchoalveolar lavage (BAL) fluid from 51 EVALI patients in 16 states and compared it to BAL fluid from 99 healthy individuals. Vitamin E acetate, also found in product samples tested by the U.S. Food and Drug Administration and state laboratories, was identified in BAL fluid from 48 of 51 EVALI patients but was not found in any BAL fluid from healthy people. OSUCCC deputy director Peter Shields, MD, says these findings support the conclusion that vitamin E acetate is a potential causative agent of EVALI.
Research Discovery Enters Phase I Clinical Testing
A new targeted oral therapy developed through research discoveries at the OSUCCC – James is being offered as an experimental treatment option for patients with certain advanced cancers, including lymphoma. The OSUCCC – James is one of four cancer centers participating in this national trial, sponsored by Prelude Therapeutics. Known only as PRT543 while in testing, this targeted treatment molecule is among the first in an emerging class of drugs called PRMT5 inhibitors. Led by Robert Baiocchi, MD, PhD, a professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James, the research team was the first to discover PRMT5 as a cancer driver and the first to develop and report a series of novel molecules to selectively inhibit PRMT5. With support from the Drug Development Institute (DDI), a translational accelerator embedded within the OSUCCC – James, this entire portfolio of molecules was licensed to Prelude.
Discovery Helps Scientists Understand Why Targeted Immuno-Oncology Drugs Sometimes Fail
OSUCCC – James researchers reported a discovery that helps scientists understand why some tumors lack immune cell infiltration and are thus unresponsive to newer PD-1 targeted therapies. PD-1 is a checkpoint protein on T cells, a type of immune cell that helps the body recognize abnormal cells in the body. PD-1 normally acts as an “off switch” to keep T cells from attacking other cells. PD-1 inhibitors are in a class of drugs called monoclonal antibodies that are used to selectively block this protein and boost immune response to attack cancer cells. Previously reported data showed that a primary reason some cancer patients do not respond to PD-1 therapy is the inability of the fighter T cells (known as CD8 T cells) to invade the tumor microenvironment. Writing in the Journal of Clinical Investigation, Yiping Yang, MD, PhD, director of the Division of Hematology at Ohio State, and colleagues report on cellular mechanisms that limit the ability of CD8 T cells to infiltrate the tumor microenvironment.
Ohio State, Nationwide Children’s Hospital Will Be First in Region to Offer ‘Flash’ Proton Therapy
A highly targeted form of proton therapy, known as “FLASH,” will be investigated in clinical trial participants with certain newly diagnosed, recurrent or advanced cancers as part of central Ohio’s first and only proton therapy center, a collaborative effort of the OSUCCC – James, Nationwide Children’s Hospital and the Ohio State Wexner Medical Center. According to preclinical data, FLASH therapy — the extremely fast application of very high radiation doses — could reduce what is typically 30 days of treatments into a single treatment that is delivered in less than a second. Scheduled to open in 2023 at an outpatient cancer center to be built on Ohio State’s west campus, the proton therapy center will offer comprehensive radiation oncology treatment options for adults and children at a single location. Proton therapy is an advanced radiation treatment that uses protons (positively charged particles) instead of X-rays to kill cancer cells.
Pilot Study Shows Even Short-Term Vaping Causes Inflammation in Non-Smokers
E-cigarette (e-cig) use is rising at concerning levels among both smokers and non-smokers, and new research data suggests that even short-term e-cig use can cause cellular inflammation in never-smoker adults. Researchers at the OSUCCC – James reported the first evidence of biological changes correlated with e-cig use in never-smokers in the journal Cancer Prevention Research. Using bronchoscopy to test for inflammation and smoking-related effects, the researchers reported a measurable increase in inflammation after four weeks of e-cig use (without nicotine or flavors). Although the change was small compared with a control group, the pilot data suggests that even short-term usage can result in inflammatory changes at a cellular level. Inflammation from smoking is an important driver of lung cancer and other respiratory diseases. Peter Shields, MD, deputy director of the OSUCCC, was senior author.
College of Pharmacy & OSUCCC – James Collaborate to Support Cancer Drug Discovery
The Ohio State University College of Pharmacy (COP) and the OSUCCC – James initiated a 10-year partnership to expand drug discovery and development in cancer and cancer-related diseases. Through this agreement, the OSUCCC – James will invest approximately $15 million for renovations of more than 19,300 square feet of the COP Division of Medicinal Chemistry and Pharmacognosy space. The OSUCCC – James also will allocate $3 million toward a Small Molecule Screening Facility that it will maintain as a shared resource with the COP. Blake Peterson, PhD, chair of the COP Division of Medicinal Chemistry and Pharmacognosy, and co-leader of the Translational Therapeutics Program at the OSUCCC – James, serves as director.
Study Suggests New Strategy for Treating Advanced, Progressing Bile Duct Cancer
A study led by OSUCCC – James researchers shows how resistance to a promising targeted drug develops in patients with a rare, lethal cancer of the bile ducts called cholangiocarcinoma. Reported in the journal Molecular Cancer Therapeutics, the study also suggests that adding another drug at the time of progression might re-sensitize tumor cells to the initial drug, called an FGFR inhibitor. While the majority of patients with FGFR-positive cholangiocarcinoma benefit from new FGFR inhibitors in clinical trials, most patients unfortunately develop cancers resistant to the drugs. Study leader Sameek Roychowdhury, MD, PhD, says researchers believe this work is an important step in understanding drug resistance and improving the treatment of this and other cancers caused by abnormal FGFR gene mutations.
Drivers of Immune Evasion, Cancer Progression Revealed by New Study
OSUCCC – James researchers led a study that has revealed how a clotting protein and blood platelets can promote cancer progression and suppress immune responses to cancer. The findings show how thrombin, a clotting protein in the blood, causes blood platelets to release transforming growth factor-beta 1 (TGF-b1), which is known for promoting disease progression in breast, prostate, colorectal and other cancers, and for suppressing immune-system responses to cancer. Also, TGF-b1 is a leading cause for the failure of immune therapies such as PD1 inhibitors in cancer patients. Principal investigator Zihai Li, MD, PhD, founding director of the Pelotonia Institute for Immuno-Oncology at the OSUCCC – James, says this study may help explain how tumors resist immune therapies and become sensitive to therapeutic agents.