Officials with GenFleet Therapeutics announced phase 2 data from the KROCUS study, fulzerasib (GFH925, KRAS G12C inhibitor) in combination with cetuximab for first-line non–small cell lung cancer (NSCLC) treatment in a late-breaking abstract at the mini oral presentation of the 2025 European Lung Cancer Congress.1
The KROCUS study is a European multicenter phase 1b/2 trial initiated in March 2023. As of the data cutoff date of January 14, 2025, 47 patients were enrolled and 45 of them received at least 1 posttreatment tumor assessment: the objective response rate (ORR) reached 80% and the disease control rate reached 100%. Median progression-free survival was 21.5 months. The posttreatment evaluation noted that 3 patients achieved complete response; 33 others reached partial response, including 1 with 100% tumor shrinkage; 57.8% of patients had >50% tumor shrinkage.
The researchers noted that 34% of enrolled patients had baseline brain metastasis, and the ORR was 71.4% per RECIST v1.1 among brain-metastatic patients who received at least 1 posttreatment tumor assessment; all nontarget lesions of brain-metastatic patients disappeared or remained stable in the course, and brain target lesions of 5 patients exhibited shrinkage.
Consistent response rates were observed in the KROCUS study across subgroups with varied PD-L1 expressions; since STK11 and KEAP1 have been identified as associated with a lower response to immunotherapy and with poor prognosis for first-line NSCLC standard of care, it’s noteworthy that similar responses were discovered in the KROCUS study between STK11 and KEAP1 wild-type patients and those with STK11 or KEAP1 co-mutations.
Grade ≥3 treatment-related adverse events (TRAEs) occurred at a considerably lower rate than that of fulzerasib monotherapy (no grade 4 or 5 TRAEs in the KROCUS study).
“I am delighted to participate in this innovative study on first-line NSCLC treatment. The encouraging efficacy data from the phase 2 trial validated investigators’ initial understanding of the study design. The trial findings also underscored the potential of this regimen, designed according to the KRAS-EGFR synergistic mechanism of the RAS pathway, to become a novel SOC [standard of care] for first-line NSCLC treatment. We are pleased that most brain-metastatic patients, without receiving anti-tumor radiotherapy prior to enrollment, were observed with notable tumor response in the trial. Moreover, the impressive safety/tolerability data bolstered our confidence in exploring KRAS-targeted therapies in first-line lung cancer treatment,” Rafael Rossell, MD, PhD, said in a press release about the findings.
“Two therapies combining KRAS inhibitors with anti-EGFR antibodies have been approved for late-line colorectal cancer treatment. We have integrated the validated mechanism of dual-target synergy with an innovative first-line setting to treat NSCLC, the tumor type with the highest prevalence of G12C mutation. This regimen is well-positioned to mitigate overlapped toxicities while effectively postponing the onset of potential resistance through the mechanistic synergy. This chemo- and immune-free combination represents a potential novel first-line SOC and leaves space for later-line immunotherapy to extend patients’ overall survival. Fulzerasib is the first KRAS G12C inhibitor launched in China and the third globally; we hope the KROCUS study will move fulzerasib forward to front-line treatment, bringing this promising combo therapy to global patients,” Yu Wang, MD, PhD, Chief Medical Officer of GenFleet, said in a release about the study.
Reference
- Majem M. First-line (1L) fulzerasib + cetuximab in KRAS G12Cm advanced NSCLC: updated efficacy and safety from KROCUS study. Presented at: 2025 European Lung Cancer Congress. March 26-29, 2025; Paris, France. Abstract LBA1.