Fulzerasib Sequential Sintilimab Plus Platinum-Doublet Neoadjuvant Therapy for Resectable KRAS G12C-Mutant NSCLC

NCT07492342 | Recruiting Phase 2

• 1 other identifier: ES-2015-162-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This is an exploratory study evaluating the efficacy and safety of neoadjuvant therapy with fulzerasib sequentially combined with sintilimab plus platinum-doublet chemotherapy in patients with resectable non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation. Approximately 30 treatment-naïve patients with stage IB-IIIA (AJCC 8th edition) NSCLC and confirmed KRAS G12C mutation will be enrolled. Eligible subjects will receive 6 weeks of fulzerasib followed by a 2-week washout period, then 3 cycles (q3w) of sintilimab plus investigator's choice of platinum-doublet chemotherapy. An end-of-treatment visit will be performed within 7 days after the last dose of neoadjuvant therapy.

Conditions

Resectable NSCLC; KRAS G12C Mutation; Stage IB-IIIA NSCLC; Neoadjuvant Therapy

Keywords

Neoadjuvant Therapy; Fulzerasib; Sintilimab; Platinum-Based Combination Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response, pCR

  The proportion of patients with no residual invasive tumor in the primary tumor and all sampled lymph nodes, as assessed by histopathological examination of the resected surgical specimen.

  At the time of definitive surgery

Secondary Outcomes (6)

• Major Pathological Response, MPR

  At the time of definitive surgery

• Objective Response Rate, ORR

  Every 6 weeks during neoadjuvant treatment, up to the time of surgery

• Complete resection rate (R0 resection)

  At the time of definitive surgery

• 2-year Event-Free Survival (EFS) rate

  From the date of study enrollment until 2 years post-enrollment

• 2-year Overall Survival (OS) rate

  From the date of study enrollment until 2 years post-enrollment

Study Arms (1)

fulzerasib+sintilimab+platinum-doublet

EXPERIMENTAL

Fulzerasib tablets: 150 mg per tablet; 600 mg orally twice daily Sintilimab injection: 100 mg (10 mL) per vial; 200 mg intravenously every 3 weeks Carboplatin injection: 100 mg (10 mL) per vial; AUC 5 intravenously every 3 weeks Cisplatin injection: 30 mg (6 mL) per vial; 75 mg/m² intravenously every 3 weeks Pemetrexed disodium for injection: 0.2 g per vial; 500 mg/m² intravenously every 3 weeks Paclitaxel albumin-bound injection: 100 mg per vial; 260 mg/m² intravenously every 3 weeks Paclitaxel injection: 30 mg (5 mL) per vial; 175 mg/m² intravenously every 3 weeks Other chemotherapeutic agents selected by the investigator, administered per the respective package insert

Drug: fulzerasib

Interventions

fulzerasib DRUG

Eligible subjects will receive 6 weeks of furzerasib followed by a 2-week washout period, then 3 cycles (q3w) of sintilimab plus investigator's choice of platinum-doublet chemotherapy.

Also known as: sintilimab, Platinum-Doublet

fulzerasib+sintilimab+platinum-doublet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the Informed Consent Form (ICF) and be able to comply with the visit and related procedures as stipulated in the protocol.
• Be male or female, aged ≥18 years old.
• Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC).
• Clinical stage IB to IIIA disease, according to the 8th edition of the TNM classification for lung cancer as defined by the International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC).
• All subjects must have a written test report before enrollment to prove the presence of KRAS G12C mutation; and must have no sensitive mutations of Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK).
• The patient is deemed by a thoracic surgeon to be a candidate for curative resection (R0 resection) and has adequate pulmonary function to undergo the planned pulmonary resection.
• Have at least one measurable lesion according to RECIST 1.1 criteria.
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Have not received any systemic anti-tumor treatment for locally advanced or metastatic NSCLC before.
• Have adequate organ and bone marrow function (subjects who have received any cell or growth factor therapy within 2 weeks before the first administration of the study drug should be excluded), defined as follows:
• \) Blood routine: Absolute neutrophil count (ANC) ≥1.5×109/L or within the normal range; platelet (PLT) count ≥100×109/L; hemoglobin (HGB) content ≥9.0 g/dL.
• \) Liver function: Serum total bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
• \) Renal function: Serum creatinine (Cr) ≤1.5×ULN or clearance of creatinine (CCr) ≥50 mL/min, calculated by the Cockcroft-Gault formula (using actual body weight); urine routine test shows urine protein \<2+; for subjects with urine protein ≥2+ at baseline as detected by urine test strips, a 24-hour urine collection should be performed and the protein content in 24-hour urine should be \<1 g (if both methods are used, the value obtained from 24-hour urine collection will be used to determine eligibility).
• \) Coagulation function: Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN and International Normalized Ratio (INR) ≤ 1.5; 11. Female subjects of childbearing age or male subjects whose partners are of childbearing age must take effective contraceptive measures throughout the treatment period and for 180 days after the treatment.
• Female subjects have evidence of postmenopausal status, or the urine or serum pregnancy test results of premenopausal female subjects are negative.

You may not qualify if:

• Histological or cytological pathology confirms the presence of small cell carcinoma, neuroendocrine carcinoma, sarcoma, lymphoepithelioma-like carcinoma, salivary gland tumors, or mesenchymal tumor components.
• Tumor invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina.
• Superior sulcus (Pancoast) tumor.
• Presence of tumor nodules in the contralateral lung lobe. Biopsy is required to confirm if contralateral lung nodules are clinically suspected.
• Documented brain metastasis. Patients with suspected brain metastasis must undergo brain imaging for further confirmation.
• Have significant cardiovascular or cerebrovascular diseases, such as:
• )Experienced definite cardiovascular abnormal events within 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or undergone angioplasty, vascular stent implantation, coronary artery bypass surgery, etc.
• )Have clinically significant QT/QTcF interval prolongation (QTcF \> 470ms for females or \> 450ms for males).
• Significant or active gastrointestinal disease characterized by diarrhea as the major symptom.
• Receipt of strong inhibitors or strong inducers of CYP3A4 or P-gp within 14 days prior to the first dose of study treatment, or within 5 half-lives of such agents (whichever is longer), or use of traditional Chinese medicine within 7 days prior to the first dose of study treatment.
• Participants who have received known CYP2D6, CYP3A4, P-gp, and BCRP sensitive substrates within 14 days or 5 half-lives (whichever is longer) before the first dose of this study, and the therapeutic window of the substrate is narrow, unless agreed by the investigator and the sponsor to be enrolled.
• Receipt of proton pump inhibitors (PPIs) or H2 receptor antagonists within 7 days prior to the first dose of study treatment.
• Systemic therapy with Chinese herbal medicines with anti-tumor indications or immunomodulatory agents (including thymopeptides, interferons, interleukins) within 2 weeks prior to the first dose of study treatment.
• Participants who are simultaneously involved in another interventional clinical study, except for observational (non-interventional) clinical studies or those in the follow-up stage after the end of an interventional study.
• Participants who have received live attenuated vaccines within 4 weeks before the first dose of study treatment or plan to receive them during the study period.

Sponsors & Collaborators

• Jianxing He: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (3)

Peking Union Medical College Hospital

Beijing, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

RECRUITING

The First Affiliated Hospital of Zhejiang University School of Medicine

Zhejiang, China

NOT YET RECRUITING

MeSH Terms

Interventions

sintilimab

Central Study Contacts

WENHUA LIANG, M.D.

CONTACT

+86-20-8337792; liangwh1987@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Thoracic Surgery

Model Details: A single-arm, phase II clinical trial evaluating the efficacy and safety of fulzerertib sequentially combined with sintilimab plus platinum-doublet chemotherapy as neoadjuvant therapy in patients with resectable non-small cell lung cancer with KRAS G12C mutation

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 25, 2026
• Study Start: January 29, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 25, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)