Dr Strickler on the Efficacy of Sotorasib Plus Panitumumab/Chemo in KRAS G12C+ mCRC

"We [presented] mature data from this [mCRC cohort], looking at both PFS, OS, and updated response, safety, and tolerability data. What we found is that the ORR was quite robust for a heavily pretreated group of patients [with mCRC] at 57%, [with] a [median] progression-free survival that exceeded eight months and a [median] OS that's very competitive with the current standard of care. [This] looks like a promising combination."

John H. Strickler, MD, a professor of medicine at Duke Cancer Institute, discussed updated safety and efficacy findings from the phase 1b CodeBreaK 101 trial (NCT04185883) evaluating sotorasib (Lumakras) in combination with panitumumab (Vectibix) and FOLFIRI (leucovorin, fluorouracil, and irinotecan) in patients with previously treated, KRAS G12C–mutated metastatic colorectal cancer (mCRC).

CodeBreaK 101 is a multi-cohort basket trial assessing sotorasib in combination with various agents in patients with various advanced tumor types. The mCRC-specific cohort focused on patients who were chemotherapy-refractory and harbored confirmed KRAS G12C mutations. Strickler emphasized that prior data had shown this triplet combination to be tolerable and associated with promising antitumor activity. The current report builds on those initial findings with more mature data for progression-free survival (PFS), overall survival (OS), and updated safety outcomes.

In this heavily pretreated patient population, the combination of sotorasib, panitumumab, and FOLFIRI demonstrated a confirmed objective response rate (ORR) of 57%, Strickler said, noting that the median PFS exceeded 8 months and OS outcomes were described as favorable when compared with historical controls in similar patient populations.

Strickler concluded by noting that these updated findings support further evaluation of the sotorasib-based triplet therapy in patients with KRAS G12C-mutant mCRC. The durability of responses and the survival outcomes observed reinforced the potential of the combination strategy to address therapeutic resistance and improve outcomes in this molecular subset.