No uniform method has been established to predict the probability of success for individual clinical trials. To help identify clinical trials with a high likelihood of offering benefit to patients, the Society for Immunotherapy of Cancer (SITC) brought together a team of experts in immuno-oncology to create a conceptual framework for potential value in phase III studies evaluating immunotherapy combinations. The framework, put forth as a checklist for the oncology community, is published in a new manuscript, “Maximizing the value of phase III trials in immuno-oncology: A checklist from the Society for Immunotherapy of Cancer (SITC),” now available in the Journal for ImmunoTherapy of Cancer, the society’s open-access, peer-reviewed online journal.
“Immuno-oncology clinical trials are of the utmost importance to provide new effective drugs for cancer patients,” said SITC President Patrick Hwu, MD. “This checklist provides investigators, and other key stakeholders, a roadmap to identify and prioritize phase III clinical trials that are likely to offer the greatest benefit to patients.”
Phase III trials are how new treatments for cancer demonstrate benefit and establish their place in the treatment paradigm to offer improved outcomes for patients. These trials are time- and resource-intensive, involving hundreds of patients and spanning multiple years. As many as half of phase III trials in oncology are unsuccessful, representing substantial losses in terms of monetary investment and opportunity for patients to receive a more effective treatment for their disease.
Clinical trials evaluating immunotherapy combinations have proliferated in recent years as immunotherapy has become the standard of care for the treatment of many cancers, offering some patients long-term remissions and even cures. Despite many successes, several recent trials of immunotherapy combinations have failed to show improvement over current treatments.
“Immunotherapy is radically different from conventional cancer treatments such as chemotherapy, which are based on directly attacking the tumor itself” says Michael B. Atkins of Georgetown Lombardi Comprehensive Cancer Center, the checklist manuscript’s first author. “Because immunotherapy treats a patient’s immune system to enable it to eliminate the tumor, phase III trials for immunotherapy combinations should consider, among many factors, the impact of the combinations on antitumor immunity and be designed with immune endpoints in mind.”
SITC’s checklist provides a simple framework to evaluate the mechanism and biology, early clinical evidence, trial design, and potential for impact of planned phase III trials evaluating immunotherapy combinations. The checklist places the highest priority on clinical data, and in cases where this is lacking, evidence of anti-tumor activity in multiple pre-clinical models, a well-defined immune mechanism of action, and a predictive biomarker to allow for selection of patients are strongly encouraged.
The release of this checklist comes on the heels of additional action SITC has brought about to address an ongoing crisis in clinical research encompassing a multitude of factors, including clinical trial administrative staffing shortages, administrative burdens, and inadequacy of current business models. The checklist may be useful to investigators in prioritizing phase III trials in response to potential overall reductions in accrual and/or increases in the number of phase III trials relative to the institution’s capacity for accrual. SITC has been leading many efforts to address the crisis, along with the checklist, to create solutions to help resolve the challenges facing the issues around clinical trials. For more information on these efforts, visit the SITC Crisis in Clinical Research web page.