Clinical Trial Evaluates New Targeted Therapy for KRAS G12c-mutant Lung Cancer and Other Malignancies

A phase 1/1b, open-label clinical trial underway at Roswell Park Comprehensive Cancer Center is taking a new approach to targeting KRAS G12C, the most common mutation in non-small cell lung cancer (NSCLC) and one that is sometimes present in colorectal cancer, pancreatic ductal adenocarcinoma and other solid tumors. The prognosis for patients with KRAS G12C-mutated tumors is typically very poor.

Although in recent years FDA approval of two KRAS G12C inhibitors (sotorasib/Lumakras and adagrasib/Krazati) made oral targeted therapies a viable treatment option for those cancers, the effectiveness of the drugs has been limited, according to Edwin Yau, MD, PhD, Assistant Professor of Oncology in the departments of Medicine and Cancer Genetics & Genomics at Roswell Park. Dr. Yau serves as the site principal investigator of “Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects with Advanced KRASG12C Mutant Solid Tumors” (NCT05462727).

“Building on what we have learned with the first generation of these medicines, which work only on the inactive form of KRAS, we are evaluating newer medications, such as RMC-6291, that target the active form of KRAS, with the hope that there will be a much-stronger anti-tumor effect,” he explains.

The clinical trial will evaluate the safety, tolerability and pharmacokinetics of escalating doses of RMC-2691, an oral KRAS inhibitor monotherapy, with the goal of identifying the maximum tolerated dose and recommended phase 2 dose. It is open to patients with advanced NSCLC, colorectal cancer, pancreatic ductal adenocarcinoma or other solid tumors with the KRAS G12C mutation whose disease has progressed despite previous treatment with chemotherapy or immunotherapy.

Sponsored by Revolution Medicines Inc., the clinical trial will enroll a total of 117 patients at Roswell Park and other centers in the U.S. and abroad.

“At Roswell Park, we are dedicated to remaining at the forefront of targeting KRAS-mutant cancers and in making these novel therapies available to our patients,” says Dr. Yau.