KROCUS Study Evaluates Fulzerasib Plus Cetuximab for NSCLC With KRAS Alteration

The combination of first-line fulzerasib plus cetuximab showed “deep and durable” responses in patients with advanced non–small cell lung cancer (NSCLC) who are harboring the KRAS G12C alteration, according to updated results from the KROCUS study.

Margarita Majem, MD, PhD, presented the results as a late-breaking abstract during the European Lung Cancer Congress 2025.

The international, single-arm, multicenter phase 2 study has been evaluating first-line fulzerasib plus cetuximab in patients with advanced NSCLC who are harboring the KRAS G12C alteration. The analysis included 47 patients who were receiving oral fulzerasib 600 mg twice daily and IV cetuximab 500 mg/m² once every 2 weeks, with a median follow-up of 12.8 months (range, 0.16-18.4 months).

The primary end point of the KROCUS study is the objective response rate. Other study end points include safety, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Researchers also investigated exploratory biomarkers.

The objective response rate was 80% among patients who were evaluable, with 57.8% showing tumor shrinkages of at least 50%. The systemic objective response rate was 71.4% in patients with brain metastases. The median PFS was 12.5 months (95% CI, 7.39-NA). The median DOR and median OS were not reached in the study. The investigators found that “responses were consistent” among patients with different PD-L1 tumor proportion scores, as well as in patients who had co-mutations in STK11 or KEAP1.

The “combination demonstrated good safety/tolerability,” investigators explained, noting that 6.4% of patients discontinued treatment and 29.8% had a reduction or interruption in treatment due to treatment-related adverse events (TRAEs). The most common TRAEs, occurring in at least 20% of patients, included rash (53.2%; grade 3 or higher, 2.1%), pruritus (31.9%; grade 3 or higher, 2.1%), asthenia (25.5%; grade 3 or higher, 2.1%), and nausea (25.5%; none grade 3 or higher).

Based on these results, the study investigators concluded that the combination treatment showed “showed deep and durable response with a favorable safety profile” and provides a chemotherapy-free treatment option for patients with advanced NSCLC who are harboring the KRAS G12C alteration.

The researchers explained that a phase 3 randomized trial with a control arm of pembrolizumab plus chemotherapy is being planned to “confirm the efficacy and safety of this novel combination” as a first-line treatment for patients with a PD-L1 tumor proportion score of less than 50%.

Reference

Tarruella MM, Gregorc V, Russo G, et al. First-line (1L) fulzerasib + cetuximab in KRAS G12Cm advanced NSCLC: updated efficacy and safety from KROCUS study. LBA1. Abstract 297MO presented at: European Lung Cancer Congress 2025; March 26-29, 2025; Paris, France.