Critical considerations for successful immunotherapy trials
There are no one-size-fits-all solutions in drug development—especially in oncology. As more research is done on the genetic drivers of diseases, and as diseases are treated using multiple modalities, the development of potentially life-saving medicines, like immunotherapies, is increasingly complex.
As new, more effective immunotherapies are developed, they provide improved benefits to patients suffering from life-threatening conditions. But, with these advances, additional questions are raised when considering how these treatments fit into overall patient treatment paradigms. When designing and executing clinical trials of cancer immunotherapies, a clear strategy for achievement of not only health authority approval but also market acceptance is critical.
More than 1,500 cancer immunotherapy drugs are in development. That number will shrink, as some will not achieve their clinical goals; and others will be withdrawn from development for strategic and/or commercial reasons. High expectations of success are set for those that do make it to market.
There are lessons that developers can learn from those agents that have cleared the hurdles and are commercially available. Foremost, clinical researchers need to have a clear vision of purpose.
“There has to be a compelling reason for bringing a new drug into the patient population,” says Bob Millham, Senior Vice President and General Manager of Hematology and Oncology at inVentiv Health, a global professional services organization that helps the biopharmaceutical industry accelerate the delivery of much-needed therapies to market. “It’s a crowded and competitive market. Therefore, clinical trial sponsors need to be aware of not only their own portfolios but also those of others, so they can see where potential challenges lie.”
Single-agent immunotherapies have been quite successful in helping patients’ immune systems fight certain cancers. Even with the significant improvements seen in overall survival, only about 25% of patients respond to single-agent treatment. Excited by the success these patients have seen, the industry is looking beyond single agents and developing dual-agent combinations for better results. One such example is PD1 with anti-PD1 antibody, or anti-PD1 with anti-PDL1 antibody, says Millham. These could be used to treat complex cancers like renal cell melanoma, blood cancer, or triple breast cancer, to name a few.
With more than 800 ongoing trials currently investigating immunotherapy agents, this is an active area of research that is producing valuable insights which can be brought forward to future trials. The challenge then becomes identifying which patient population is appropriate for which combination.
“You have to work with the characteristics of those patients, do a deeper analysis of the biology of those who have done well, and those who have not,” he says. “Data mining and running new experiments on tissue, looking at the characteristics of the targeted tumor — all are clues to better determining the right combination that will work on the right patient at the right time.”
“With immunotherapy, you’re not just finding and eradicating a tumor, you’re using the patient’s immune system to help fight the disease,” Millham explains. “There are extra unknown dimensions you have to wrestle with that make it challenging.”
“While there is a lot to still learn about agent combinations," he adds, “each new discovery provides the opportunity for more thoughtful intent of drug development and the ability to work with increased future clarity.”
Immunotherapies cannot achieve success without the help of patients willing to enroll in trials to uncover the right combinations. Recruiting the right patients for the right immunotherapy trial is an art form. But when successful, they have the capability to provide considerable survival benefits.
The obstacles to patient selection may be mitigated by the use of biomarkers to identify patients who may benefit from a trial, even while there is still a need to determine which biomarker will impact treatment outcomes. And when you factor in combination immunotherapies, the complexity of recruiting the right patients increases. When looking at two therapies that use two different biomarkers to determine therapy, which biomarker takes the lead in determining patient study?
“Sponsors must take a close look at the data generated from these trials,” says Millham, “and understand what happens with different patient selection, entry data, and biomarkers. Using that information, sponsors can better design future trials that have the needed protocol, vendors, and investigators, all of which allows for faster enrollment,” he adds.
New advances in immunotherapies are fueling more drug development and discovery. Designing a trial that recruits the right patient for the targeted therapy, or combination therapy, and that will benefit the patient most requires an in-depth look at the measures needed for the desired outcome.
“Simply understanding tumor response is not sufficient to develop an effective immunotherapy,” says Millham. “Trial sponsors must have in place endpoints, standard responses and protocols, and thorough observation and investigation to create trials that are successful and beneficial to patients.”
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