Highlights from AACR 2024
Early-stage cancer research companies from all over the globe gathered in San Diego during the AACR Annual Meeting. More than 23,200 registrants (including more than 22,000 in-person registrants) from 78 countries and territories participated in the meeting. With 630 speakers and 450 exhibitors covering topics from population science and prevention to cancer biology, translational studies, spatial biology, clinical research, survivorship, and advocacy, the latest advances from some of the best minds in cancer research shared insights and data.
More than 240 clinical trials were presented, which includes the largest-ever clinical program at AACR with 24 featured Phase III trials and several practice-changing studies. Additionally, we saw multiple areas of advancing technologies highlighted such as immunotherapy, precision medicine, AI, and big data, as well as combination therapies.
Watching the transition from a fledgling technology to robust, validate-able assays, I am confident that the evolving spatial biology technologies will drive more robust patient stratification and deeper knowledge of mechanism of action. The result being faster and more accurate enrollment which can drive timelines to be decreased.
Accelerated approvals
Accelerated approvals were a hot topic during the meeting with Richard Pazdur, M.D., Director, Oncology Center of Excellence (OCE), U.S. Food and Drug Administration (FDA), who discussed the need to “level the playing field.” The agency recently gained the authority to require companies to have a confirmatory trial underway at the time of an accelerated approval—and to reject a drug if that prerequisite is not met—thanks to the Food and Drug Omnibus Reform Act of 2022. The rejection of Regeneron’s submission caused a stir around the FDA’s definition of “well underway” for a confirmatory trial, perhaps because they had only begun the safety lead-in. The FDA these days wants drug companies to have early discussions with the agency about their “comprehensive development plans,” including the confirmatory trial design and timing, Pazdur said. One program Pazdur would like to see more advancement on is Project Pragmatica, which explores ways to simplify clinical trials in terms of patient eligibility criteria and trial endpoints.
Cancer vaccines
Cancer vaccines are showing their potential with BioNTech, Gritstone, Geneos, and Merck/Moderna presenting data this year. This included a late stage personalized vaccine in development. While the consensus is that vaccines are not ready to be standard of care, they can be helpful in certain populations. The primary goal is to tackle minimal residual disease, which is when cancer is not detectable on radiographical images, but malignant cells can be found via a blood test. This is particularly common in blood cancers but can also occur with solid tumors.
New modalities like mRNA are helping to drive more effective T-cell activation and ideally steering more effective studies. Moderna is developing vaccine mRNA-4157 with Merck. The partners revealed plans for a Phase III trial for July 2024 to test the vaccine in combination with Keytruda for post-surgery treatment of patients with resected melanoma at high risk of recurrence.
Additionally, Geneos presented data for a DNA personalized cancer vaccine for patients with unresectable, advanced metastatic hepatocellular carcinoma (HCC), where 10-year survival is only about 5%. The trial featured 36 patients who received the vaccine and Merck & Co.’s which showed a 30.6% objective response rate. The response rate in this type of cancer is typically about 11% to 18%. Three patients have had complete responses and one patient achieved secondary resectability.
Big data and AI in oncology studies
AI and big data made a big splash starting with the plenary session focused on cutting-edge technologies with a focus on spatial biology as a tool to study the tumor microenvironment in unprecedented detail and decipher many of its complexities. Deeper understanding of cancer biology and mechanisms requires a deep understanding of the intricate relationships that exist between cancers and their microenvironments. Coupling high-plex and low-plex validation will help to ensure data provides robust support for biomarker driven patient selection.
In addition to all the sessions mentioned above, I was thrilled to attend “Methods Workshop: Choosing and Using Antibodies for Spatial Informed Protein Expression” presented by Arutha Kulasinghe, Ph.D., Scientific Director (QSBC) and Group Leader of the Clinical-oMx Lab at the University of Queensland, David Rimm, M.D., Professor of Pathology, Yale University, and Anja Roden, M.D., Pathologist, Mayo Clinic. The discussion centered on antibodies in quantitative applications, including in a CAP/CLIA setting.
“It’s a super exciting time for spatial transcriptomics and proteomics evolving rapidly in front of us. AACR showed us maturity in spatial studies from large clinical cohort studies and new data analytics giving us deeper functional insights into the tumor and immune cell biology,” Kulasinghe said. “It’s no longer only about cell phenotypes but all the functional flavors of cells and their locations. Understanding these cellular subsets is likely to provide a deeper understanding of the cells which may play a role in improving responses to therapy.”
While these are just a few of the highlights from AACR 2024, these show that as an industry we are making significant progress. With the recent increase in biologics, cell and gene therapy, along with antibody drug conjugates (ADCs) and vaccines, the future of oncology drug development is moving at a rapid clip towards safer more effective treatments.
