A phase 1 clinical trial underway at Roswell Park Comprehensive Cancer Center will evaluate the potential of a “molecular glue” to treat MAPK pathway-mutated advanced solid tumors in patients who have exhausted standard treatment options. Preclinical studies of NST-628 demonstrated that the drug resulted in significantly longer survival in RAS- or RAF-mutant patient-derived xenograft models. Investigators believe it also has the potential to overcome treatment resistance.
“This clinical trial is specifically for patients who harbor RAS mutations of all different histologies and also for melanoma patients who harbor the non-canonical BRAF mutations,” says Igor Puzanov, MD, MSCI, FACP, Senior Vice President of Clinical Investigation and Director of the Center for Early Phase Clinical Trials at Roswell Park. Dr. Puzanov serves as site principal investigator for the clinical trial, “A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects with Solid Tumors” (NCT06326411).
RAS mutations are present in about 20% of all human cancers, most pancreatic (95%) and colorectal (50%) tumors, and about 30% of lung tumors. RAF mutations are associated with approximately half of all melanomas and more than half of all papillary thyroid cancers, and are also present in breast, ovarian, colon and prostate tumors. Both are associated with treatment resistance.
The single-arm, non-randomized study is open to patients at least 18 years old who have a metastatic or locally advanced solid tumor and for whom no viable standard-of-care therapy is available. It comprises two parts — dose escalation and dose expansion — with each requiring different tumor characteristics. Part A will determine the maximum tolerated dose, while Part B will evaluate safety and the objective tumor response rate.
Sponsored by Nested Therapeutics Inc., the study expects to enroll 230 patients at 10 locations in the U.S. and Australia; Roswell Park is one of only six sites in the U.S.
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