Dupert (fulzerasib) / GenFleet Therap, Innovent Biologics - LARVOL DELTA

First-line (1L) fulzerasib + cetuximab in KRAS G12Cm advanced NSCLC: Updated efficacy and safety from KROCUS study (ELCC 2025) - P1/2 | "Clinical trial identification NCT05756153 Legal entity responsible for the study Zhejiang GenFleet Therapeutics Co., Ltd Funding Zhejiang GenFleet Therapeutics Co., Ltd Background Upstream activation of epidermal growth factor receptor (EGFR) has been identified as a dominant mechanism underlying resistance to KRAS inhibition. Conclusions The combination of FUL + CETU showed deep and durable response with a favorable safety profile in 1L KRAS G12Cm NSCLC pts, providing a chemo-free treatment option. A phase III randomized trial with control of pembrolizumab plus chemotherapy is being planned to confirm the efficacy and safety of this novel combination in pts with PDL1 TPS < 50% in the 1L"

Clinical • IO biomarker • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • KEAP1 • KRAS • STK11

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. (ASCO 2024) - P1/2 | "The preliminary data from ongoing KROCUS study has demonstrated very promising efficacy and favorable safety profile of fulzerasib + cetuximab in the first line setting of KRAS G12C mutated NSCLC. More data will be generated to provide clinical evidence supporting this combination as a potential frontline therapy."

Clinical • Combination therapy • IO biomarker • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Efficacy and safety of KRAS G12C inhibitor IBI351 monotherapy in patients with advanced non-small cell lung cancer: results from a phase 2 pivotal study. (PubMed, J Thorac Oncol) - "IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC."

IO biomarker • Journal • Metastases • Monotherapy • P2 data • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRINP3 • KEAP1 • KRAS • PIK3CG • SMAD4 • STK11 • TP53

KRAS G12C Inhibitor IBI351 In Patients (pts) with Advanced Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Pivotal Phase 2 Study (IASLC-WCLC 2024) - "Mutation in STK11 also showed significant association with higher tumor burden at baseline and lower response rate (p <0.05). Conclusions : In KRAS G12C mutant NSCLC, updated results of IBI351 monotherapy continues to support its role as a new treatment option with sustained efficacy and manageable safety."

Clinical • IO biomarker • Metastases • P2 data • Anemia • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRINP3 • KEAP1 • KRAS • PIK3CG • SMAD4 • STK11 • TP53

In the updated NRDL, Dupert (fulzerasib) is newly listed for the treatment of advanced NSCLC adult patients harboring KRAS G12C mutation who have received at least one systemic therapy (PRNewswire)

Reimbursement • Non Small Cell Lung Cancer

GFH925X1101: A Study of GFH925 in Patients With Advanced Solid Tumors With KRAS G12C Mutations (clinicaltrials.gov) - P1/2 | N=334 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Recruiting ➔ Completed | Trial completion date: Apr 2024 ➔ Dec 2024

Trial completion • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS

Efficacy and Safety Evaluation of Fulzerasib in the Treatment of Advanced NSCLC with KRAS G12C Mutation: A Multicenter, Non-Interventional, Observational Study (IBI351-RWS-001) (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

ASS1 and EGFR in KRAS G12C mutant lung cancer predicts response to KRAS G12C inhibitors (ESMO 2025) - "In this study, we investigated the synergistic effects of fulzerasib or sotorasib in combination with cetuximab in KRAS-mutant lung cancer cell lines, along with analysis of RAS signalling rebound. Legal entity responsible for the study R. Rosell. Funding GenFleet Therapeutics."

Lung Cancer • Oncology • Solid Tumor • ASS1 • CDC37 • EGFR • ERRFI1 • HSP90AA1 • KEAP1 • KRAS • YAP1

Fulzerasib plus cetuximab prevents resistance in KRAS G12C NSCLC suppressing NRF2, AURKA and PRMT1 (ESMO 2025) - "This study investigates the antitumor effect and mechanisms of fulzerasib or sotorasib combined with cetuximab in KRAS G12C NSCLC cell lines, focusing on the interplay between AURKA/PRMT1 and NRF2 pathways. Legal entity responsible for the study R. Rosell. Funding GenFleet Therapeutics."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • KRAS • PHGDH • PRMT1 • PSAT1 • SLC7A11

Advances in Diagnosis and Targeted Therapy of KRASG12C Mutant Non-small Cell Lung Cancer (PubMed, Zhongguo Fei Ai Za Zhi) - "In targeted therapies, KRASG12C targeted drugs, including Sotorasib, Adagrasib, Fulzerasib, Garsorasib, and Glecirasib, have demonstrated certain therapeutic efficacies in clinical trials and have obtained marketing approval. To tackle drug resistance and enhance patient's prognoses, combination therapeutic strategies that integrate targeted agents with chemotherapy, immune checkpoint inhibitors, Src homology region 2 domain-containing phosphatase 2 (SHP2) inhibitors, and epidermal growth factor receptor (EGFR) monoclonal antibodies have emerged. This paper systematically reviews the advancements in the diagnosis and targeted therapy of NSCLC with KRASG12C mutation, aiming to offer a reference for the selection of clinical treatment regimens and subsequent research.."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS

Efficacy and safety of fulzerasib in patients (pts) with KRAS G12C-mutant non-small cell lung cancer (NSCLC): Updated results from phase I/II studies (ESMO 2025) - P1/2 | "Conclusions Long-term follow-up of IBI351 continues to show encouraging efficacy with manageable safety in KRAS G12C-mutant NSCLC pts. The confirmatory study and further clinical development of IBI351 are ongoing."

Clinical • IO biomarker • P1/2 data • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Real-World Study of IBI351 for KRAS G12C+ NSCLC in China (clinicaltrials.gov) - P=N/A | N=600 | Not yet recruiting | Sponsor: Guangdong Association of Clinical Trials

New trial • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

IBI351 Plus Cetuximab β in Untreated Advanced Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: Guangdong Association of Clinical Trials

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Fumarate and Ass1 in KRAS-Mutant NSCLC: The Influence of Cetuximab in Combination With KRAS G12C Inhibitors (Sotorasib and Fulzerasib) (IASLC-WCLC 2025) - "Low ASS1 expression is shown to harbour a poor prognosis. Further research could clarify the relevance of ASS1 and fumarate as a biomarker and therapeutic target."

Combination therapy • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ASS1 • CDC37 • EGFR • ERBB3 • ERRFI1 • FASN • HSP90AA1 • KRAS • YAP1

Fulzerasib, a KRAS-G12C Inhibitor, Has Synergistic Antitumor Effect With Omeprazole Pretreatment in KRAS G12C NSCLC (IASLC-WCLC 2025) - "Fulzerasib (GFH925, IBI351), an irreversible KRAS G12C inhibitor, has demonstrated superior efficacy compared to sotorasib and adagrasib, achieving an objective response rate of 49.1% and a median progression-free survival of 9.7 months. Omeprazole, a proton pump inhibitor, has been shown to enhance cytoplasmic retention of cytotoxic drugs and sensitize cancer cells to chemotherapy and some target therapy, such as tepotinib...Conclusions : This study highlights that fulzerasib exhibits synergistic antitumor effects with omeprazole pretreatment, potentially through the suppression of multiple cancer-related proteins and pathways. Future studies will explore additional mechanisms, including autophagy and ferroptosis, to further elucidate the therapeutic potential of this combination."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTNNB1 • HES1 • KRAS • SNAI2

Discovery and preclinical characterization of KRAS G12C inhibitor fulzerasib (GFH925) for advanced solid tumors (ACS-Fall 2025) - "Notably, in the MIA PaCa-2 and NCI-H358 CDX models, the anti-tumor efficacy of GFH925 was superior to sotorasib at the same dose. In the NCI-H2122 NSCLC model, the concurrent administration of GFH925 and cetuximab significantly suppressed tumor growth and demonstrated preferable synergy in antitumor effects. The comprehensive preclinical evaluation of the rationally designed KRAS G12C inhibitor fulzerasib (GFH925) sets a solid foundation for its rapid clinical advancement in KRAS G12C-driven malignancies."

Metastases • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP3A4 • KRAS

Literature review of advances and challenges in KRAS G12C mutant non-small cell lung cancer. (PubMed, Transl Lung Cancer Res) - "The KRAS G12C mutation was once considered "undruggable" until the breakthrough approval of two targeted inhibitors: AMG510 (sotorasib) and MRTX849 (adagrasib). In China, IBI351 and D-1553 have also been approved for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation...Notably, recent findings indicate that combining dual immune checkpoint inhibitors (ICIs; durvalumab and tremelimumab) with chemotherapy (CT) in patients with advanced NSCLC, including those with KRAS mutations, can result in durable survival benefits...Moreover, the POSEIDON trial has highlighted the potential of dual ICI therapy combined with CT to achieve sustained clinical benefits. Despite these advances, the heterogeneity of tumor responses underscores the need for further investigation into intrinsic resistance mechanisms and the strategic optimization of combination therapies to enhance treatment outcomes."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KROCUS: A Study of GFH925 in Combination With Cetuximab in Previously Untreated Advanced NSCLC Harboring KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=47 | Completed | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Application of Fulzerasib in advanced NSCLC pts with KRAS G12C mutation, a indication application demonstration project (ChiCTR) - P4 | N=486 | Not yet recruiting | Sponsor: Shanghai Chest Hospital; Shanghai Chest Hospital

New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRASG12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies. (PubMed, Signal Transduct Target Ther) - P1, P1/2 | "No TRAEs resulted in treatment discontinuation. IBI351 demonstrated encouraging clinical efficacy and a manageable safety profile in KRASG12C inhibitor-naïve Chinese patients with KRASG12C-mutated metastatic CRC."

Journal • Monotherapy • P1 data • Retrospective data • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • KRAS

Discovery of Fulzerasib (GFH925) for the Treatment of KRAS G12C-Mutated Solid Tumors. (PubMed, J Med Chem) - "This molecule demonstrates high in vitro potency and selectivity, favorable pharmacokinetic profiles across species, and significant in vivo antitumor efficacy in various cancer-related xenograft models, including intracranial tumors. Fulzerasib has recently received accelerated approval in China for adult NSCLC patients with the KRAS G12C mutation after prior systemic therapy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

IBI3019, a first-in-class EGFR/CDH17/CD16A tri-specific antibody, demonstrated potent efficacy against CRC and an excellent safety profile in preclinical studies (AACR 2025) - "Inhibition of EGFR signaling is clinically effective in colorectal cancer (CRC) as evidenced by the approval for Cetuximab in combination with chemotherapy or Encorafenib, a BRAF inhibitor, and the promising clinical results when combined with KRAS inhibitors, such as Adagrasib or Sotorasib...Additionally, IBI3019 incorporates a high affinity CD16A single domain antibody that mediates stronger antibody-dependent cell cytotoxicity (ADCC) than IgG1 used in Cetuximab or the low fucosylated Fc of Amivantamab, a bispecific antibody targeting c-MET and EGFR, both in vitro and in vivo...It exhibited strong synergy with Fulzerasib, a KRAS G12C inhibitor and MRTX1133, a KRAS-G12D inhibitor...IBI3019 is a highly optimized FIC molecule with enhanced EGFR blocking capability and ADCC, maximizing tumor inhibition while minimizing toxicity. Its superior efficacy and safety profile support further clinical evaluation."

Preclinical • Trispecific • Colorectal Cancer • Oncology • Solid Tumor • CDH17 • FCGR3A • KRAS • MET

An overview of PROTACs targeting KRAS and SOS1 as antitumor agents. (PubMed, Bioorg Med Chem Lett) - "Currently, four KRASG12C-specific inhibitors, namely sotorasib, adagrasib, fulzerasib and garsorasib, have garnered regulatory approval. PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. This article provides an overview of the chemical structures, design strategies, structure-activity relationship (SAR) studies as well as in vitro and in vivo activities of the PROTACs degrading KRAS and SOS1, and sheds light on future challenges and opportunities to accelerate the development of new chemotherapies for KRAS-driven cancers."

Journal • Review • Oncology • Targeted Protein Degradation • KRAS

The Efficacy and Safety of IBI351, Cetuximab β Combined With FOLFIRI as First-line /IBI351, Cetuximab β as Second-line in the Treatment of KRAS G12C-mutated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

A Multicenter, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Fulzerasib (IBI351) in Combination With Ivonescimab (AK-112) in First-line Treatment of Advanced or Metastatic Non-small Cell Lung Cancer Patients With KRAS G12C Mutation (clinicaltrials.gov) - P2 | N=39 | Not yet recruiting | Sponsor: Shanghai Chest Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor