GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the phase II trial data of KROCUS Study, fulzerasib (GFH925, KRAS G12C inhibitor) in combination with cetuximab for first-line non-small cell lung cancer (NSCLC) treatment，at the 2024 American Society of Clinical Oncology (ASCO) annual meeting.
The preliminary result of the trial was accepted as a late-breaking abstract and selected for oral presentation at the clinical science symposium of lung cancer treatment, highlighting the combination therapy’s promising efficacy and its excellent safety/tolerability profile. Notably, this marks the first time that a KRAS G12C inhibitor is combined with an EGFR inhibitor as a first-line NSCLC treatment with its data presented at a global academic event.
The KROCUS Study, led by renowned lung cancer expert Dr. Rafael Rosell, is a European multi-center phase Ib/II study initiated in March 2023. As of April 19 this year, a total of 40 subjects were enrolled and 33 of them received at least one available post-treatment tumor assessment: the objective response rate (ORR) reached 81.8% and the disease control rate (DCR) reached 100%. The post-treatment evaluation revealed that most patients (27/33) exhibited tumor response: one patient achieved complete response; the other two achieved partial response with a shrinkage in their tumor size by 100%.
Additionally, the combination therapy demonstrated a favorable safety/tolerability profile, with both treatment-related adverse events (TRAEs) and TRAEs above grade 3 occurring at a lower rate than those in the fulzerasib monotherapy study in second line and above NSCLC. The data was presented by Dr. Vanesa Gregorc from Italy’s Candiolo Cancer Institute, Italy.
The new drug application for fulzerasib monotherapy in treating advanced KRAS G12C-mutant NSCLC has been accepted and granted priority review designation by China’s National Medical Products Administration (NMPA). Based on the data presented at 2023 ESMO Asia, the registrational phase II study of GFH925 monotherapy for NSCLC showed an ORR of 46.6% and a DCR of 90.5%; the median progression-free survival (mPFS) was 8.3 months. In addition, fulzerasib monotherapy received two breakthrough designations for advanced G12C-mutant NSCLC and metastatic colorectal cancer (CRC) patients.
Dr. Rafael Rosell
Principal Investigator of KROCUS study
“I am delighted that the preliminary data of this phase II trial was selected for oral presentation at ASCO, an acknowledgement of this innovative combination therapy's potential in treating NSCLC patient in a of first-line setting. Currently, there are multiple global trials exploring the combination of KRAS G12C and EGFR inhibitors for later-line CRC. However, GenFleet is propelling the validation of this synergistic mechanism further into first-line treatment for NSCLC, the cancer type with the largest G12C-mutant patient population. We eagerly anticipate the trial's continued progress, aiming to offer more frontline options for patients worldwide. ”
Yu Wang, M.D.,Ph.D.
Chief Medical Officer of GenFleet
“The design of the KROCUS Study is based on deep research into synergistic mechanisms, animal models validation, as well as clinical data generated from the fulzerasib monotherapy in the second-line setting. We are excited to see that the preliminary data from our first-line combination study exceeding our expectation. Furthermore, this chemo- and immuno-free combination could potentially mitigate overlapped toxicities and delay drug resistance, leaving space to allow later-line immunotherapy to extend the patients' overall survival.”
KROCUS: a Phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC
Presenter: Dr. Vanesa Gregorc
Abstract No. : LBA8511
A total of 40 treatment naïve advanced KRAS G12C positive NSCLC patients were treated with GFH925 in combination with cetuximab (fulzerasib 600mg BID + cetuximab 500 mg/m2 Q2W) as of April 19, 2024. Most patients (95%) were diagnosed with stage IV disease and 13 (32.5%) patients with brain metastases.
Efficacy: As of cutoff date, of the 33 patients who received at least one post-treatment tumor assessment, investigator-assessed ORR was 81.8% (95% CI: 64.5, 93.0) and DCR was 100% (95% CI: 89.4, 100); ORR among patients with brain metastasis was 70%. The median duration of response (DoR) was not reached yet and 88% of patients were still on treatment with a median follow-up of 5.1 months.
Safety: As of cutoff date, the combination therapy was well tolerated. Treatment-related adverse events (TRAEs) occurred in 87.5% of subjects and the majority of the TRAEs were grade 1-2. About 17.5% of subjects reported grade 3 TRAEs. There were no grade 4-5 TRAEs. No new safety signals were identified compared with fulzerasib or cetuximab as single agent.
About GenFleet Therapeutics
GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet’s proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP.
Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan), the United States, Europe and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with numerous publicly listed companies worldwide.
GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.
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