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Resectable NSCLCPhase 2K-NADIRNCT07492342

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

A Phase 2 study testing fulzerasib in people with Resectable NSCLC and KRAS G12C Mutation, run by Jianxing He at 3 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
fulzerasib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
3 sitesChina
Study dates
29 Jan 2026to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 1) 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.
  • 2) Liver function: Serum total bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
  • 3) 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).
  • 4) 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.
  • 12.Female subjects have evidence of postmenopausal status, or the urine or serum pregnancy test results of premenopausal female subjects are negative.

Who cannot join

  • 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:
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  • 1)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.
  • 2)Have clinically significant QT/QTcF interval prolongation (QTcF > 470ms for females or > 450ms for males).
  • 7.Significant or active gastrointestinal disease characterized by diarrhea as the major symptom.
  • 8.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.
  • 9.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.
  • 10.Receipt of proton pump inhibitors (PPIs) or H2 receptor antagonists within 7 days prior to the first dose of study treatment.
  • 11.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.
  • 12.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.
  • 13.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.
  • Note: Inactivated virus vaccines for seasonal influenza by injection are allowed within 4 weeks before the first dose of study treatment; however, live attenuated influenza vaccines are not allowed.
  • 14.Patients requiring long-term systemic corticosteroid use. Any other form of immunosuppressive therapy within 7 days prior to randomization.
  • Note: Topical glucocorticoids (nasal, inhaled, or other routes), physiological doses of systemic glucocorticoids (≤10 mg/day prednisone or equivalent), or use for pre-medication (e.g., prevention of contrast agent allergy) are permitted.
  • 15.Major surgical procedure (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment, or presence of non-healing wounds, ulcers, or fractures.
  • 16.History of radiation pneumonitis, idiopathic pneumonitis, active pneumonitis, pulmonary fibrosis, diffuse interstitial lung disease, or organizing pneumonia (e.g., bronchiolitis obliterans).
  • 17.Participants with known allergies to study treatment or any of its components.
  • 18.Known primary immunodeficiency. 19.Active autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis [excluding diverticulosis], celiac disease, systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis (Wegener's syndrome), Graves' disease, hypophysitis, uveitis, etc.), or history of such disease within the previous 2 years.
  • Patients with vitiligo, psoriasis, alopecia that do not require systemic therapy within the past 2 years, hypothyroidism requiring only thyroid hormone replacement, and type 1 diabetes mellitus requiring only insulin replacement are eligible.
  • 20.Have major acute or chronic infections, including:
  • Active infections requiring systemic treatment;
  • Positive human immunodeficiency virus antibody (HIV-Ab) at baseline;
  • Active hepatitis B virus (HBV) infection (positive HBsAg and positive HBV-DNA). For patients with negative HBsAg and positive HBcAb, HBV-DNA testing is required; patients with positive HBV-DNA are excluded;
  • Active hepatitis C virus (HCV) infection (positive HCV-Ab and positive HCV-RNA);
  • Active pulmonary tuberculosis,, receiving anti-tuberculosis therapy, or having received anti-tuberculosis therapy within 1 year prior to the first dose of study treatment
  • Active syphilis. 21.History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • 22.Diagnosis of another malignancy within 5 years prior to the first dose,except for radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin,radically resected carcinoma in situ, radically treated localized prostate cancer, papillary thyroid carcinoma, and similar diseases.
  • 23.Uncontrolled concurrent disease, including:
  • 1)Serious infection occurring within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; or therapeutic oral or intravenous antibiotics administered within 2 weeks prior to initiation of study treatment; 2)Symptomatic congestive heart failure (New York Heart Association Class III-IV), left ventricular ejection fraction (LVEF) < 50% by echocardiography, or uncontrolled cardiac arrhythmia; 3)Uncontrolled hypertension despite standard therapy (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg); 4)Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium, or serum calcium >12 mg/dL, or corrected serum calcium > ULN); 5)Esophageal or gastric varices requiring immediate intervention (e.g., banding or sclerotherapy), or subjects with evidence of portal hypertension (including splenomegaly on imaging) or a history of variceal bleeding considered to be at high risk of bleeding by the investigator or in consultation with a gastroenterologist or hepatologist; endoscopic evaluation must be performed within 3 months prior to enrollment; 6)History of deep vein thrombosis or any other severe thromboembolism within 3 months prior to enrollment (implanted venous access port or catheter-related thrombosis, or superficial venous thrombosis is not considered severe); 7）Any life-threatening hemorrhagic event within 3 months prior to enrollment; 8)Uncontrolled metabolic disorders or other acute or chronic non-malignant organ or systemic diseases, or paraneoplastic syndromes that may confer high medical risk and/or uncertainty in survival assessment; 9)History of gastrointestinal perforation and/or fistula within 6 months prior to enrollment; 10)Subjects at risk of intestinal obstruction or perforation (including but not limited to acute diverticulitis, intra-abdominal abscess, history of intra-abdominal cancer), or history of extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea; 11)Significant malnutrition requiring intravenous nutritional supplementation, unless malnutrition had been corrected for more than 4 weeks prior to the first dose of study treatment; 12)Post-placement of intraluminal esophageal or tracheal stents; 13)Other acute or chronic medical conditions that may increase risk related to study participation or study drug administration, interfere with the interpretation of study results, or are deemed by the investigator to render the subject ineligible for the study; 14)Neurological, psychiatric, or social conditions that would impair compliance with study requirements, significantly increase the risk of adverse events, or affect the subject's ability to provide written informed consent (e.g., schizophrenia, history of drug abuse, etc.).
  • 24.Pregnant or lactating women

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

WENHUA LIANG, M.D. contact

+86-20-8337792

liangwh1987@163.com

China3 sites, 3 recruiting

  • Peking Union Medical College Hospital

    Beijing

    YEYE CHEN, M.D., +86 13671338819, chenyeye@pumch.cn

    Not yet recruiting

  • The First Affiliated Hospital of Guangzhou Medical University

    Guangzhou

    WENHAU LIANG, M.D., +86-20-8337792, liangwh1987@163.com

    Recruiting

  • The First Affiliated Hospital of Zhejiang University School of Medicine

    Zhejiang

    JIAN HU, M.D.

    Not yet recruiting

Other trials in China

About this study

Official title: Evaluation of Efficacy and Safety of Fulzerasib Sequentially Combined With Sintilimab Plus Platinum-Doublet Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer With KRAS G12 Mutation: a Single-Arm, Phase II Clinical Trial

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.

Read the detailed description

Following neoadjuvant therapy, subjects without disease progression (per RECIST 1.1) and meeting criteria for radical resection will undergo curative surgery within 7-28 days after the last dose of neoadjuvant therapy. Subjects with disease progression (per RECIST 1.1) or who do not meet criteria for radical resection will discontinue study treatment. Subjects assessed with disease progression during neoadjuvant therapy will also discontinue study treatment, with subsequent therapy at the investigator's discretion; subjects without disease progression will continue to complete remaining neoadjuvant therapy. Adjuvant and other postoperative therapy will be determined by the investigator.

Pathologic complete response (pCR) and major pathologic response (MPR) rates will be evaluated by the investigator in resected pathological specimens according to the International Expert Consensus on Neoadjuvant Immunotherapy for NSCLC.

Clinical tumor imaging assessments will be performed by the investigator per RECIST 1.1. Preoperative imaging will include at least neck, chest, abdomen, and pelvis (after 6 weeks of neoadjuvant targeted therapy and before sequential chemo-immunotherapy, and 7-28 days after the last neoadjuvant treatment and prior to surgery). Tumor assessment will be performed 14-28 days after surgery as the postoperative baseline, to be completed before the first adjuvant therapy. Imaging assessments will then be conducted every 12 weeks (±7 days) post-baseline for up to 2 years, or until disease progression, withdrawal, loss to follow-up, death, or other protocol-specified criteria, whichever occurs first.

Being tested
fulzerasib
Keywords
Neoadjuvant Therapy, Fulzerasib, Sintilimab, Platinum-Based Combination Chemotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fulzerasibDrug

    Also called sintilimab, Platinum-Doublet

    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.

Study groups in NCT07492342
Study groupRoleWhat they receive
fulzerasib+sintilimab+platinum-doubletExperimentalFulzerasib 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
Receives: Drug: fulzerasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At the time of definitive surgery

Secondary outcomes (6)

  1. Major Pathological Response, MPR

    The proportion of patients with ≤10% residual viable tumor cells in the primary tumor, as assessed by histopathological examination of the resected surgical specimen.

    Measured: At the time of definitive surgery

  2. Objective Response Rate, ORR

    The proportion of patients achieving a complete or partial response according to RECIST v1.1, as assessed by the investigator.

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

  3. Complete resection rate (R0 resection)

    The proportion of patients who achieve a complete (R0) resection of all known disease, as determined by the surgeon and pathologist at the time of definitive surgical resection.

    Measured: At the time of definitive surgery

  4. 2-year Event-Free Survival (EFS) rate

    The proportion of patients alive and free from disease recurrence, progression, or death from any cause at 2 years after study enrollment. Event-free survival will be estimated using the Kaplan-Meier method.

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

  5. 2-year Overall Survival (OS) rate

    The proportion of patients alive at 2 years after study enrollment. Overall survival will be estimated using the Kaplan-Meier method.

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

  6. Treatment Emergent Adverse Event, TEAE;Treatment-related Adverse Event, TRAE;Immune-related AE, irAE;Serious Adverse Event, SAE

    The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: From the first dose of study treatment up to 30 days after the last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2026
  2. Study start29 Jan 2026
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07492342
Sponsor's protocol ID
ES-2015-162-02
Acronym
K-NADIR
Status last verified
Jan 2026
First submitted
19 Mar 2026
Last updated
25 Mar 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing fulzerasib in people with Resectable NSCLC and KRAS G12C Mutation, run by Jianxing He at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact WENHUA LIANG, M.D. (+86-20-8337792, liangwh1987@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response, pCR (time frame: At the time of definitive surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07492342.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.

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