GenFleet Therapeutics(2595.HK) announced the publication of phase II data from the KROCUS study in The Lancet Oncology (Impact Factor: 35.9), with KROCUS representing the world’s first KRAS+EGFR dual-targeting regimen for first-line treatment of KRAS G12C-mutated non-small cell lung cancer (NSCLC). The phase II data from this multi-center European trial were previously highlighted in a late-breaking abstract for mini oral presentation at the 2025 European Lung Cancer Conference. Preliminary data from the KROCUS study was already selected as a late-breaking research abstract and featured in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Fulzerasib, the first KRAS G12C inhibitor approved in China and the third globally, was launched in the Chinese mainland for advanced KRAS G12C-mutated NSCLC in August 2024 and was added to the National Reimbursement Drug List in December 2025 (effective from January 2026). As to global development, GenFleet initiated a European multi-center KROCUS study led by lung cancer expert Dr. Rafael Rosell in March 2023. As of the data cutoff date, the regimen achieved an objective response rate (ORR) of 80%, disease control rate (DCR) of 100%, and median progression-free survival (PFS) of 12.5 months among evaluable patients. The regimen also delivered notable activity in patients with brain metastases, maintained high dose intensity of both agents throughout treatment, and will preserve subsequent standard-of-care treatment options for patients.
“This publication of phase II data from GenFleet’s global multi-center trial validates the innovative first-line combination strategy of the KROCUS study featuring fulzerasib, and charted a groundbreaking paradigm for front-line strategies in global development of RAS-inhibiting therapies.” stated Jiong Lan, Ph.D., Chief Executive Officer of GenFleet.
Commentary on Lancet Oncology and from European media agencies
Dr. Adrian Sacher, a thoracic oncologist from University of Toronto and Princess Margaret Cancer Center in Canada, published a commentary article on the KROCUS study in the journal. He stated that the field of direct KRAS inhibitor therapy in NSCLC will inevitably evolve rapidly between KRAS G12C (OFF) inhibitor combinations and novel KRAS(ON) and pan-Ras inhibitor strategies. “The findings of this study highlight the transformative potential of rational combination informed by a careful understanding of the biology underpinning drug resistance and toxicity: the use of this combination is compelling given the potential of this strategy to overcome the mechanisms of resistance while simultaneously circumventing autoimmune hepatoxicity via use of these agents in anti-PD-1 immunotherapy-naive population. Indeed, the authors demonstrate an impressive response rate associated with this combination, even among refractory subsets, including PD-L1-negative and STK11 or KEAP1 co-mutated tumors, without a signal of concerning hepatotoxicity.”
In addition, major European media agencies, including ANSA, DIRE, and askanews, covered the publication. “Non-small cell lung cancer accounts for approximately 85% of cases, and at least 13% of these cases are characterized by the KRAS G12C mutation,” Vanesa Gregorc, investigator of the KROCUS study, stated in these reports, “Unlike traditional therapies that combine chemotherapy, the KROCUS study combines only targeted therapies for tumors. We have moved away from indiscriminately attacking all cells and adopted a more selective molecular-level approach that spares patients the most severe side effects. Notably, the combo regimen including fulzerasib does not exhibit the liver or intestinal toxicities typical of other KRAS G12C inhibitors, limiting side effects to manageable skin reactions.”
Systematic, rigorous mechanistic studies support dual-target combination therapy for first-line treatment
The synergistic antitumor activity of fulzerasib in combination with cetuximab was supported by GenFleet’s systematic and rigorous preclinical research data, which were published in the Journal of Medicinal Chemistry (2025) and Cell Death Discovery (2026): in various KRAS G12C-mutant cell lines and animal models, the preclinical studies demonstrated significantly greater inhibition of tumor growth and cell proliferation than either agent alone, together with prolonged mice survival. The dual inhibition of KRAS G12C and EGFR exerted deep and synergistic activity by overcoming the key resistance mechanisms to KRAS G12C inhibitor monotherapy, including blocking EGFR-mediated feedback reactivation, KRAS resynthesis, and the conversion of KRAS G12C to its active GTP-bound state. This dual-target strategy had already been clinically validated in colorectal cancer (CRC), where two regimens combining a KRAS G12C inhibitor and an EGFR antibody were approved by US FDA for late-line CRC, providing mechanistic rationale for expanding this approach into the front-line NSCLC treatment.
Outstanding Efficacy Establishes Potential 1L SOC
KROCUS was a single-arm, multicenter phase Ib/II trial conducted across 30 hospitals in Europe and all trial participants received fulzerasib at 600 mg BID plus cetuximab at 500 mg/m² Q2W in 28-day cycles. As of January 14, 2025, the combination trial achieved an ORR of 80% (cORR of 69%) and a DCR of 100% among 45 evaluable patients. The median time to response was 1.8 months, median PFS 12.5 months, and 12-month overall survival rate 70%; median duration of response was not yet reached.
KROCUS also demonstrated consistent efficacy across key molecular subgroups in KRAS G12C–mutant NSCLC, with robust activity regardless of PD-L1 expression and high response rates even in patients with STK11, KEAP1 or SMARCA4 co-mutations - identified as being associated with lower response and poor prognosis to standard chemo- and immuno- treatments.
The combination regimen demonstrated a favorable safety profile, with no new safety signals identified relative to fulzerasib or cetuximab monotherapy. The median relative dose intensity reached 98.2% for fulzerasib and 95.3% for cetuximab, supporting consistent and stable dose delivery with minimal interruptions. In addition, the combination trial showed a clear safety advantage over fulzerasib monotherapy, and an improved safety window compared with chemo-immunotherapy or other KRAS+EGFR regimens. Treatment-related adverse events (TRAEs) occurred in 87% of patients, mostly graded 1 or 2; only 15% of patients experienced grade 3 TRAEs, and no grade 4 or 5 cases were reported. Most TRAEs were mild-to-moderate skin reactions associated with cetuximab, and no patients discontinued treatment due to fulzerasib-related toxicities.
Diversified combo strategies for indications with substantial unmet needs
The KROCUS regimen is an integral component of GenFleet’s broad portfolio of combination strategies, spanning across combo studies, bispecific/multi-specific antibodies, and novel conjugate platforms. These approaches are designed to harness synergies between upstream-downstream targets within a single pathway or across different targets in multiple complimentary pathways. Leveraging insights from breakthroughs in basic research and practical clinical needs, GenFleet is dedicated to advancing single‑agent treatments to multi‑pathway regimens across all lines of therapy and developing the most suitable mono or combo therapy for each indication. Now the Company has established a RAS-focused and diversified pipeline to address evolving medical needs in major indications including pancreatic cancer, non-small-cell lung cancer, and cancer cachexia.
About Dupert® (fulzerasib, KRAS G12C Inhibitor)
Discovered by GenFleet Therapeutics, fulzerasib (GFH925/IBI351) is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.
In September 2021, GenFleet Therapeutics and Innovent entered into an exclusive license agreement for the development and commercialization of GFH925 in China (including the Chinese mainland, Hong Kong, Macau and Taiwan).
In January 2023, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for fulzerasib for the treatment of patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. In May 2023, the CDE of China’s NMPA granted another BTD for fulzerasib for the treatment of advanced CRC patients with KRAS G12C mutation who have received at least two systemic therapies. In August 2024, the CDE of NMPA has approved fulzerasib for the treatment of advanced NSCLC patients harboring KRAS G12C mutation who have received at least one systemic therapy.
About GenFleet Therapeutics
With a focus on cutting-edge therapies, GenFleet Therapeutics is dedicated to serving significant unmet medical needs globally in oncology and immunology. Leveraging its deep understanding of disease biology and translational medicine, GenFleet has established a proprietary and fully integrated R&D system that yields a robust pipeline of 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 spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe.
The company has set up a highly differentiated RAS-targeted matrix including selective and pan-RAS inhibitors of diverse molecular types, with most assets leading their categories in clinical progress in China or globally. In addition, the company has pioneered a series of first-in-class combination therapies based on dual-target synergistic mechanisms. By integrating clinical needs and insights, GenFleet is dedicated to expanding its portfolio into major therapeutic areas including pancreatic cancer, NSCLC, and cachexia. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world.
Forward-looking Statements
Specific information in this press release may contain or constitute forward-looking words that are not historical facts. They can be identified by using forward-looking terminology, such as "predict", "believe", "plan", "predict", "expect", "will", "may", "should" and other words of similar meanings.
Based on the management's current beliefs, plans, estimates and expectations of the company's operation and market trends subject to changes beyond control, the forward-looking terminology reflects GenFleet Therapeutics' beliefs, plans, estimates and expectations of future development. Actual outcome in the future may differ significantly from forward-looking words owing to market, policy, and R&D uncertainties, among others.
Subject to the above-mentioned uncertainties, GenFleet Therapeutics makes no expressed or implied guarantee as to the accuracy, completeness or feasibility of this presentation, and you are cautioned not to solely rely on such forward-looking words.
Neither the company nor any of its directors, officers, employees, shareholders, agents, related parties, consultants or representatives will be liable to you or any other person for consequences resulting from using this presentation. Investors are advised to exercise due diligence with reference to the company's official disclosures for decision-making.
