New collaborative study to investigate sequential combinations of targeted inhibitors and immunotherapies against cancer

Study to understand how to rationally sequence and combine mutation-targeted and immunotherapies for cutaneous melanoma receives $13.3M National Cancer Institute grant

The National Cancer Institute has awarded a five-year, $13.3 million grant to a collaborative study on sequential combinations of targeted inhibitors and immunotherapies against cancer.

Dr. Roger Lo, professor of medicine/dermatology and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center, is the lead UCLA investigator on the program – called Spatiotemporal Tumor Analytics for Guiding Sequential Targeted Inhibitor-Immunotherapy Combinations, or ST-Analytics. He said this research effort is designed to determine if recent advances in treatment can yield greater patient benefit when rationally administered in specific sequence before combination rather than as simultaneously administered combinations.

“The pace of developing individual cancer therapies has really accelerated over the past decade, so ST-Analytics is timely in aiming to accelerate progress by sequencing and combining these therapies, based on molecular-computational models, for maximal clinical benefit,” said Lo, who will also lead efforts on patient-like animal models that have already yielded early insights into the importance of sequencing these types of therapies to treat melanoma brain metastasis.

The research program is headed by the Institute for Systems Biology (ISB), a nonprofit biomedical research organization based in Seattle, which will work with researchers at UCLA and Yale University to provide a research environment that will bring together scientists with high levels of clinical, biological, computational and experimental expertise, removing barriers to the free flow of data, biospecimens and ideas. Collaborators from all three institutions will work to train and educate the next-generation of systems biologists focused on cancer, drawing especially from underserved communities.

Timing, not just dosage, is a major component of the NCI-funded program. Researchers will use state-of-the-art tools to study tumors at set points in treatment regimens with varying efficacies and will build computational models of how tumors respond. They will study mouse models, validate their findings with biobanked human tissues, and design clinical trial concepts.

Dr. Jim Heath, the president of ISB, who is leading the study, said there have been some recent clinical trials to combine targeted inhibitors with cancer immunotherapies, but combining the approaches has proved very challenging.

“This has been very frustrating for researchers and clinicians, but there is emerging evidence that starting these therapies in specific sequences before their combination might extract the most benefits for the patients. We aim to develop a working model of how to do sequential and combinatorial therapies that will inform the design of clinical trials,” he said. “The relationship between targeted inhibitors and immunotherapies in their multidimensional interactions is a systems biology problem that ISB and our collaborators are uniquely positioned and qualified to handle.”