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

Fulzerasib in Combination With Omeprazole Pretreatment and/or Terbinafine in KRAS G12C Mutant Lung Cancer Cell Lines (IASLC-WCLC 2026) - "Introduction : Fulzerasib plus cetuximab demonstrate significant clinical outcomes in KRAS G12C-mutant NSCLC patients (Gregorc et al. Western blot analysis confirms the broad shutdown effect of the triple combination on multiple receptors and critical downstream effectors that confer resistance to KRAS G12C inhibitors. Clinical translational relevance warrants being highlighted."

Combination therapy • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • EGFR • HES1 • KEAP1 • KRAS • SOX2 • SQLE • 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

Fulzerasib combined with HDAC inhibitors (Entinostat) and Vitamin E succinate in KRASG12C lung cancer cell lines (ESMO 2026) - No abstract available

Preclinical • Lung Cancer • Oncology • Solid Tumor • KRAS

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

KRAS-Targeted Therapies in NSCLC: Resistance, Combination Strategies, and Emerging Clinical Paradigms. (PubMed, Med Oncol) - "Sotorasib and adagrasib achieve ORRs of 37-43% and median PFS ~ 6-7 months in previously treated KRAS G12C NSCLC, with improved tolerability over docetaxel. Next-generation inhibitors (olomorasib, divarasib, glecirasib, D-1553, IBI351) demonstrate ORRs 45-55% and, in some studies, PFS exceeding first-generation agents, while emerging KRAS G12D inhibitors show early proof-of-concept activity...KRAS-mutant NSCLC is transitioning from historically untargetable disease to a therapeutically actionable subset. Future progress hinges on resistance-directed combinations, biomarker-guided personalization, expansion to non-G12C mutants, and evaluation in earlier disease settings."

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

Efficacy and Safety of IBI351 plus Cetuximabβ ± FOLFIRI in Patients with KRAS G12C-Mutated Metastatic Colorectal Cancer (the Crucial Study) (ESMO 2026) - No abstract available

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • KRAS

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

A Study of IBI351 in Combination With Cetuximab in Subjects With KRAS G12C Mutated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | N=80 ➔ 8 | Recruiting ➔ Terminated; company development strategy adjustment

Enrollment change • Trial termination • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Development and Validation of a Sensitive UHPLC-MS/MS Analytical Method for Fulzerasib in Rat Plasma and its Application to Pharmacokinetics Studies. (PubMed, Biomed Chromatogr) - "Chromatographic separation was achieved within a 4.0-min run on a C18 column, with verapamil as the internal standard and detection via multiple reaction monitoring. Fulzerasib exhibited favorable pharmacokinetic properties, including low plasma clearance (5.02 mL/min/kg), moderate volume of distribution and notably high oral bioavailability of 38.6%. The established method is reliable, efficient and readily applicable, thereby providing a vital tool for accelerating the ongoing preclinical and translational research of Fulzerasib."

Journal • PK/PD data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Efficacy and Safety of IBI351 in Combination With Chemotherapy in Advanced Non-squamous Non-small Cell Lung Cancer Subjects With KRAS G12C Mutation (clinicaltrials.gov) - P3 | N=144 | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Phase classification: P1 ➔ P3

Phase classification • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Trial of HRS-7058 in Advanced or Metastatic Non-Small Cell Lung Cancer Patients Who Have Failed Standard Treatment (clinicaltrials.gov) - P3 | N=450 | Not yet recruiting | Sponsor: Shandong Suncadia Medicine Co., Ltd.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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 | Enrolling by invitation | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University | Not yet recruiting ➔ Enrolling by invitation | Trial completion date: Nov 2027 ➔ Dec 2028 | Trial primary completion date: Nov 2027 ➔ May 2027

Enrollment open • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • KRAS

FALCO: Neoadjuvant Treatment of Fulzerasib Plus Cetuximab N01 in KRAS G12C Mutated Locally Advanced Colorectal Cancer With or Without Resectable Metastases (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Zhejiang University

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

K-NADIR: Fulzerasib Sequential Sintilimab Plus Platinum-Doublet Neoadjuvant Therapy for Resectable KRAS G12C-Mutant NSCLC (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Jianxing He

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

Fulzerasib plus cetuximab in first-line KRASG12C-mutated non-small-cell lung cancer (KROCUS): a single-arm, multicentre, phase 1b/2 trial. (PubMed, Lancet Oncol) - P1/2 | "In treatment-naive KRASG12C-mutated NSCLC, fulzerasib plus cetuximab showed encouraging activity with a favourable safety profile. The combination is currently being planned for investigation in a phase 3 study."

Journal • P1/2 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=55 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P2 trial • 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 | Recruiting | Sponsor: Guangdong Association of Clinical Trials | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Cetuximab co-treatment with KRAS G12C inhibitors fulzerasib and sotorasib in human KRAS G12C non-small cell lung cancer cells. (PubMed, Cell Death Discov) - "Notably, the cotreatment response of H358 cells mirrors clinical trials with KRAS G12C colorectal cancer and NSCLC patients, where the combination of cetuximab with KRAS G12C inhibitors resulted in increased response and progression-free survival. Our findings provide insight into further tailoring EGFR inhibitor cotreatment in KRAS G12C NSCLC patients."

Journal • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AKT1 • ASS1 • ERRFI1 • KRAS • YAP1

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