Sotorasib Significantly Improves Progression-Free Survival for KRAS G12C-Mutated Non-Small Cell Lung Cancer in Phase 3 Trial

Sotorasib (Lumakras; Amgen), a once-daily oral treatment for KRAS G12C-mutated non-small cell lung cancer (NSCLC), met the primary endpoint of a phase 3 trial showing superior progression-free survival (PFS) against the intravenous chemotherapy, docetaxel, according to findings presented at the European Society for Medical Oncology (ESMO) Congress 2022.

Sotorasib also met the key secondary endpoint of higher objective response rate (ORR).

"The totality of evidence from this study supports Lumakras as an important targeted treatment option for patients with non-small cell lung cancer who harbor the KRAS G12C mutation and reinforces the critical need for comprehensive biomarker testing for all patients with advanced disease," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release.

The randomized, active-controlled phase 3 CodeBreak 200 is part of the CodeBreak clinical development program evaluating sotorasib on advanced solid tumors in patients with KRAS G12C-mutated NSCLC. CodeBreak 200 compared sotorasib to docetaxel in 345 patients who were previously treated for locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC.

The Blinded Independent Central Review (BICR) determined that sotorasib increased PFS to 1 year in 25% of patients administered sotorasib compared with 10% of patients administered docetaxel. Further, 28% of patients in the sotorasib cohort achieved the higher ORR endpoint, showing an improved disease control rate of 83%; however, neither treatment had a significantly higher overall survival rate (OS).

Presenting study author Melissa L. Johnson, MD, director of Lung Cancer Research at the Sarah Cannon Research Institute at Tennessee Oncology, said that the CodeBreak 200 trial was the first to show benefits for heavily pretreated KRAS patients who have limited treatment options.

"It is encouraging that progression-free survival benefits were consistent across all clinically relevant subgroups, and that sotorasib response rates were more than double compared to docetaxel response rates,” Johnson said in the press release. “[These] data represent a major advance for the treatment of patients with KRAS G12C-mutated non-small cell lung cancer."

Sotorasib also had fewer grade 3 and serious treatment-related adverse effects (TRAEs) than docetaxel. The most common TRAEs were diarrhea, fatigue, alopecia, nausea, and anemia.

Sotorasib is the only KRAS inhibitor approved in worldwide markets. New studies are looking at its efficacy for other types of solid tumors.

"We plan to submit this data to health authorities around the world where Lumakras/Lumykras is conditionally approved, and we look forward to our discussions with regulators," Reese said in the press release.

Lung cancer accounts for more deaths than colon cancer, breast cancer, and prostate cancer combined, and is the top cause of cancer-related deaths. For NSCLC patients with metastatic disease, the 5-year survival rate is only 8%.

The KRAS G12C mutation is the most common KRAS mutation for this type of cancer but has few secondary treatment options—among secondary treatments, the average PFS rate is 4 months.

Reference

Amgen. LUMAKRAS®/LUMYKRAS® (SOTORASIB) DEMONSTRATES SUPERIOR PROGRESSION-FREE SURVIVAL OVER DOCETAXEL IN FIRST POSITIVE PHASE 3 TRIAL OF A KRAS G12C INHIBITOR IN NON-SMALL CELL LUNG CANCER. Amgen website. September 11, 2022. Accessed on September 12, 2022. https://www.amgen.com/newsroom/press-releases/2022/09/lumakraslumykras-sotorasib-demonstrates-superior-progressionfree-survival-over-docetaxel-in-first-positive-phase-3-trial-of-a-kras-g12c-inhibitor-in-nonsmall-cell-lung-cancer