On December 18, 2024 Break Through Cancer reported to have launched a collaborative cohort for a Phase 1 study of RMC-6236, a compound developed by Revolution Medicines that is designed to suppress multiple RAS proteins that drive human cancers, including pancreatic cancer, non-small cell lung cancer and colorectal cancer (Press release, Break Through Cancer, DEC 18, 2024, View Source;utm_medium=rss&utm_campaign=collaboration-with-revolution-medicines-to-study-biomarkers-for-rason-multi-selective-inhibitor-in-pancreatic-cancer [SID1234649193]).
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The ongoing phase 1 trial of RMC-6236 (NCT05379985) is exploring the safety, tolerability and antitumor activity of RMC-6236 in patients with common KRAS mutations (including G12D, G12V and G12R) in metastatic pancreatic ductal adenocarcinoma (PDAC)— the most common and highly aggressive type of pancreatic cancer, with an average 5-year survival rate of only 3% for metastatic cases. Patient blood and tumor tissue samples from a dedicated collaboration cohort within this trial will be analyzed by The Conquering KRAS in Pancreatic Cancer TeamLab, funded jointly by Break Through Cancer and the Lustgarten Foundation, using advanced multi-omic and spatial profiling approaches to search for biomarkers able to predict tumor response and how cancer cells adapt to the therapy. Such biomarkers are being studied to help doctors quickly know if a patient is or is not responding to a therapy, and whether they would benefit from combination therapies.
Beyond assessing patient outcomes, the trial is uniquely designed to deepen the understanding of the biology of KRAS-mutant pancreatic cancers. By studying patient samples and biopsies in the lab, researchers will use advanced technologies to explore how PDAC evolves under treatment, the biological impact of RAS inhibition, and the mechanisms underlying resistance. This comprehensive approach will provide critical insights into the complex interplay of tumor biology and drug response.
Cancer-causing RAS proteins drive a significant number of all human cancers, including over 90% of PDAC, and many KRAS G12 mutations in particular are prevalent in human cancers. Many KRAS-targeted cancer therapies target only single KRAS mutations, while RMC-6236 was designed to inhibit the full spectrum of cancer-causing KRAS mutations, as well as other cancer-causing RAS family member mutations as well.
"We’re delighted to have the opportunity to work with Break Through Cancer and the Lustgarten Foundation on this unique cohort within our Phase 1 study for RMC-6236," said Wei Lin, M.D., Chief Medical Officer at Revolution Medicines. "The funded investigators at Break Through Cancer will use the latest scientific techniques to examine the biological effects of RMC-6236 on pancreatic tumors in patients in our clinical trial. We hope to glean insights into the mechanisms of response and resistance to RMC-6236, which will guide us to develop potential combination therapies based on our RAS(ON) inhibitors to improve patient outcomes."
The multi-center trial is being conducted by Revolution Medicines with clinical investigators at Break Through Cancer participating institutions, including Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, The University of Texas MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center. The work is powered by Break Through Cancer’s TeamLab model of "radical collaboration," which enables real-time data and discovery sharing in laboratories across these clinical sites and in MIT’s Koch Institute for Integrative Cancer Research. Alongside this trial, TeamLab members are also investigating mechanisms of resistance to RMC-6236 and are searching for additional signaling pathways that could be promising targets for future therapeutics.
"Our mission is to drive innovation through collaboration, and this trial represents an extraordinary opportunity to do just that," said Tyler Jacks, president of Break Through Cancer; founding director of MIT’s Koch Institute for Integrative Cancer Research; David H. Koch (1962) Professor of Biology. "Together with Revolution Medicines and our TeamLab investigators, we’re applying advanced technologies and multi-institutional expertise to tackle one of the toughest challenges in oncology – pancreatic cancer.