Researchers from The College of Texas MD Anderson Most cancers Middle will current promising outcomes from medical trials in three minisymposia abstracts on the American Affiliation for Most cancers Analysis (AACR) Annual Assembly 2025. Findings embody a customized vaccine mixture remedy for colorectal most cancers, using radiotherapy to keep away from the toxicities of systemic therapies for kidney most cancers, and engineered exosomes to silence mutant KRAS in pancreatic most cancers.
Along with these trials, forthcoming press releases will characteristic notable oral and plenary session abstracts. Extra info on all MD Anderson AACR Annual Assembly content material may be discovered at MDAnderson.org/AACR.
Personalised vaccine with or with out immunotherapy is protected for sufferers with metastatic colorectal most cancers subtype (Summary CT012)
Sufferers with microsatellite-stable metastatic colorectal most cancers (MSS mCRC) have poor outcomes and restricted therapy choices after failure of normal chemotherapy, partially due to an immunologically “chilly” tumor microenvironment. Researchers led by Saurav Daniel Haldar, M.D., and Michael Overman, M.D., developed a customized vaccine platform referred to as NeoAg-VAX that makes use of bioinformatics and sequencing instruments to ship as much as 10 tumor-derived proteins focused to every affected person’s particular mixture of mutations. On this Part I feasibility examine, the researchers mixed the customized vaccine with and with out pembrolizumab immunotherapy in 28 sufferers with MSS mCRC. The customized vaccine was protected and possible to manage, resulting in robust immune responses in most sufferers vaccinated on this examine. The researchers additionally characterised immune cell composition inside sufferers’ tumors, offering molecular insights into the immune microenvironment that would inform future therapeutic approaches. Haldar will current the outcomes April 27.
Metastasis-directed radiation remedy avoids toxicities of systemic remedy in sufferers with clear cell renal cell carcinoma (Summary CT132)
Systemic therapies used for sufferers with metastatic clear cell renal cell carcinoma (ccRCC), corresponding to immunotherapy and tyrosine kinase inhibitors, are related to excessive toxicity charges. Metastasis-directed radiation remedy could restrict unintended effects, however there aren’t any established biomarkers to establish sufferers probably to reply. Due to this fact, researchers led by Chad Tang, M.D., and Pavlos Msaouel, M.D., Ph.D., performed a Part II potential trial investigating metastasis-directed remedy with out systemic remedy in 121 sufferers with oligometastatic ccRCC. The median progression-free survival (PFS) was 18 months, with a median of 34 months systemic therapy-free survival (STFS). Importantly, total survival (OS) was not compromised, with OS charges of 94% and 87% at two and three years, respectively. The researchers additionally examined a novel tumor-informed circulating tumor DNA (ctDNA) assay to detect molecular residual illness (MRD). Sufferers who have been MRD- versus MRD+ at baseline had median STFS of 54 months in comparison with 27 months. These findings present that metastasis-directed radiation remedy may help sufferers keep away from systemic therapies with out compromising outcomes and that the ctDNA assay is a helpful customized prognostic biomarker for response. Tang will current the outcomes April 28.
Exosomes ship gene silencers for KRAS G12D pancreatic most cancers (Summary CT265)
KRAS G12D mutations happen in over 40% of pancreatic most cancers instances, however KRAS inhibitors haven’t yielded sturdy responses for sufferers, partly resulting from an immunosuppressive tumor microenvironment. Exosomes are small extracellular vesicles that may be engineered to hold small interfering RNA (siRNA), which silence particular genes, into most cancers cells. In a first-in-human Part 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 using engineered exosomes derived from bone marrow cells to silence KRAS G12D in 12 sufferers with metastatic pancreatic most cancers. Six of the 12 sufferers receiving all exosome doses had steady illness in goal lesions, and there have been no dose-limiting toxicities. The researchers famous a discount in KRAS G12D circulating DNA post-treatment. Additional in vivo evaluation revealed that these exosomes would work nicely with immune checkpoint blockade to reprogram the tumor microenvironment and overcome therapy resistance, highlighting the mixture as a possible therapeutic technique being investigated in an upcoming Part II trial. LeBleu will current the outcomes April 29.
As well as, Summary CT267 options early medical trial knowledge from the ATR kinase inhibitor, ART0380, in superior stable tumors. This focused remedy was initially found and developed by MD Anderson’s Therapeutics Discovery division and licensed to Artios Pharma. Preclinical and translational research led by investigators at MD Anderson, revealed in Scientific Most cancers Analysis, demonstrated potent antitumor exercise and established an revolutionary strategy to optimize affected person choice primarily based on molecular tumor options.
