Where the Rubber Meets the Road
BY DARRELL E. WARD
Clinical trials culminate years of laboratory and preclinical research. They determine whether promising experimental agents will benefit people and prevent, treat or perhaps even cure a form of cancer.
Pelotonia funds support two clinical trials at the OSUCCC – James: an early-phase study of a novel anticancer vaccine to prevent several types of solid tumors, and a safety and efficacy trial of a promising agent for treating chronic lymphocytic leukemia (CLL).
A Novel Anticancer Vaccine
Pravin Kaumaya, PhD, professor and director of the Vaccine Research Division in the Department of Obstetrics and Gynecology, led development of this experimental vaccine, which targets two cell-surface receptors that help sustain many types of cancer.
The vaccine targets two specific regions of the human epidermal growth factor receptor 2 (HER-2), a molecule that occurs at abnormally high levels in up to 30 percent of breast cancers. In addition, the vaccine targets HER-1 (also called epidermal growth factor receptor, or EGFR), a molecule overexpressed in many other solid tumors, including ovarian, renal, colon, lung and gastrointestinal cancers.
The phase I trial will determine the safety and optimal dose of the vaccine, evaluate whether it shows therapeutic benefit by stimulating the immune system to respond to the patient’s tumor, and document any clinical responses that may occur. The study also includes an innovative efficacy arm that was approved by the U.S. Food and Drug Administration. The trial (ClinicalTrials.gov identifier NCT01376505) was open to accrual in August 2011 and has completed cohort 1 (six patients, dose level 1). The second cohort opened March 1, 2012.
Kaumaya led development of the protocol for the trial and serves as the trial’s overall chair. Clinical principal investigator for the trial is Tanios Bekaii-Saab, MD, assistant professor of Medicine and of Pharmacology, and medical director of Gastrointestinal Oncology. Co-principal investigator is William Carson III, MD, professor of Surgery and associate director for clinical research at the OSUCCC
“Pelotonia funds are extremely important for this trial,” Kaumaya says. “They pay for needed pharmacy services, tests for patients and the purchase of vaccine adjuvants, and they help support correlative studies.”
A Promising Targeted Agent for Treatment of CLL
Chronic lymphocytic leukemia (CLL) is the most common leukemia diagnosed in the United States, with an annual incidence of about 15,000 and mortality of about 4,400. The treatment of CLL has greatly improved over the last three decades, but relapse is inevitable so new therapies are needed.
This safety and efficacy trial, which is led by John C. Byrd, MD, director of Hematology and professor of Medicine, of Medicinal Chemistry and of Veterinary Biosciences, evaluates a promising agent called ibrutinib (formerly PCI-32765) in combination with a monoclonal antibody called ofatumumab.
Ibrutinib is the first drug designed to target Bruton’s tyrosine kinase, a protein that is essential for CLL-cell survival and proliferation. Earlier trials evaluating ibrutinib as a single agent at the OSUCCC – James and elsewhere have shown promising results.
“This is an exciting agent,” says Byrd, who is a member of the OSUCCC – James Experimental Therapeutics and Innate Immunity programs and holds the D. Warren Brown Designated Chair of Leukemia Research. “It seems to be a highly active oral therapeutic that produces remissions that often last months on end in patients with relapsed and refractory CLL. These responses last for many months in part because patients are willing to remain on the drug since the side effects are very tolerable.”
Amy Johnson, PhD, assistant professor of medicine at the OSUCCC – James, co-led preclinical research on ibrutinib showing that the agent is selective for B lymphocytes.
The trial combining ibrutinib with ofatumumab (OSU-10053, PCYC-1109) is being performed only at Ohio State in people with relapsed or refractory CLL, small lymphocytic lymphoma or prolymphocytic leukemia. “The commitment of Pelotonia funds to this trial is important,” Byrd says. “Pelotonia dollars will support the patient-care costs associated with the trial.”