Researchers from The University of Texas MD Anderson Cancer Center will present promising results from clinical trials in three minisymposia abstracts at the American Association for Cancer Research (AACR) Annual Meeting 2025. Findings include a personalized vaccine combination therapy for colorectal cancer, the use of radiotherapy to avoid the toxicities of systemic treatments for kidney cancer, and engineered exosomes to silence mutant KRAS in pancreatic cancer.
In addition to these trials, forthcoming press releases will feature notable oral and plenary session abstracts. More information on all MD Anderson AACR Annual Meeting content can be found at MDAnderson.org/AACR.
Personalized vaccine with or without immunotherapy is safe for patients with metastatic colorectal cancer subtype (Abstract CT012)
Patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC) have poor outcomes and limited treatment options after failure of standard chemotherapy, in part because of an immunologically "cold" tumor microenvironment. Researchers led by Saurav Daniel Haldar, M.D., and Michael Overman, M.D., developed a personalized vaccine platform called NeoAg-VAX that uses bioinformatics and sequencing tools to deliver up to 10 tumor-derived proteins targeted to each patient's specific combination of mutations. In this Phase I feasibility study, the researchers combined the personalized vaccine with and without pembrolizumab immunotherapy in 28 patients with MSS mCRC. The personalized vaccine was safe and feasible to administer, leading to strong immune responses in most patients vaccinated on this study. The researchers also characterized immune cell composition within patients' tumors, providing molecular insights into the immune microenvironment that could inform future therapeutic approaches. Haldar will present the results April 27.
Metastasis-directed radiation therapy avoids toxicities of systemic therapy in patients with clear cell renal cell carcinoma (Abstract CT132)
Systemic therapies used for patients with metastatic clear cell renal cell carcinoma (ccRCC), such as immunotherapy and tyrosine kinase inhibitors, are associated with high toxicity rates. Metastasis-directed radiation therapy may limit side effects, but there are no established biomarkers to identify patients most likely to respond. Therefore, researchers led by Chad Tang, M.D., and Pavlos Msaouel, M.D., Ph.D., conducted a Phase II prospective trial investigating metastasis-directed therapy without systemic therapy in 121 patients with oligometastatic ccRCC. The median progression-free survival (PFS) was 18 months, with a median of 34 months systemic therapy-free survival (STFS). Importantly, overall survival (OS) was not compromised, with OS rates of 94% and 87% at two and three years, respectively. The researchers also tested a novel tumor-informed circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD). Patients who were MRD- versus MRD+ at baseline had median STFS of 54 months compared to 27 months. These findings show that metastasis-directed radiation therapy can help patients avoid systemic therapies without compromising outcomes and that the ctDNA assay is a useful personalized prognostic biomarker for response. Tang will present the results April 28.
Exosomes deliver gene silencers for KRAS G12D pancreatic cancer (Abstract CT265)
KRAS G12D mutations occur in over 40% of pancreatic cancer cases, but KRAS inhibitors have not yielded durable responses for patients, partly due to an immunosuppressive tumor microenvironment. Exosomes are small extracellular vesicles that can be engineered to carry small interfering RNA (siRNA), which silence specific genes, into cancer cells. In a first-in-human Phase I dose escalation trial, researchers led by Valerie LeBleu, M.D., Ph.D., Shubham Pant, M.D., Elizabeth Shpall, M.D., and Brandon Smaglo, M.D., examined the use of engineered exosomes derived from bone marrow cells to silence KRAS G12D in 12 patients with metastatic pancreatic cancer. Six of the 12 patients receiving all exosome doses had stable disease in target lesions, and there were no dose-limiting toxicities. The researchers noted a reduction in KRAS G12D circulating DNA post-treatment. Further in vivo analysis revealed that these exosomes would work well with immune checkpoint blockade to reprogram the tumor microenvironment and overcome treatment resistance, highlighting the combination as a potential therapeutic strategy being investigated in an upcoming Phase II trial. LeBleu will present the results April 29.
In addition, Abstract CT267 features early clinical trial data from the ATR kinase inhibitor, ART0380, in advanced solid tumors. This targeted therapy was initially discovered and developed by MD Anderson's Therapeutics Discovery division and licensed to Artios Pharma. Preclinical and translational studies led by investigators at MD Anderson, published in Clinical Cancer Research, demonstrated potent antitumor activity and established an innovative approach to optimize patient selection based on molecular tumor features.
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