Phase II Neoadjuvant Study of Garsorasib Followed by Ivonescimab Plus Chemotherapy in Resectable Stage IIA-IIIB KRAS G12C-Mutant NSCLC (GIVEN Study)

NCT07472478 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2025-981-03
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a multicenter, prospective, open-label clinical trial. It enrolls previously untreated patients with resectable stage IB-IIIB KRAS G12C mutation-positive NSCLC to evaluate the efficacy and safety of glesorasib sequentially combined with ivonescimab and chemotherapy as perioperative treatment for this patient population.

Conditions

Lung Cancer (NSCLC); KRAS G12C Lung Cancer

Keywords

lung cancer; KRAS; KRAS G12C

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy

  14-24 weeks

Secondary Outcomes (6)

• Major Pathological Response (MPR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy

  14-24 weeks

• R0 resection rate

  24 months

• Objective Response Rate (ORR)

  From initiation of neoadjuvant therapy until the final preoperative imaging assessment, up to 24 weeks (each cycle is 3 weeks).

• One-year event-free survival rate (1-y EFS%)

  12 months

• Event-Free Survival (EFS)

  From the date of first dose until the end of event-free status (disease progression, recurrence, or death from any cause), assessed up to 60 months.

Study Arms (1)

Neoadjuvant therapy phase

EXPERIMENTAL

sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.

Drug: Garsorasib; Drug: Ivonescimab Combined With Chemotherapy; Procedure: Surgery; Drug: Ivonescimab; Behavioral: Observation

Interventions

Garsorasib DRUG

Garsorasib 600 mg, twice daily, for 4 to 6 weeks

Neoadjuvant therapy phase

Ivonescimab Combined With Chemotherapy DRUG

After a 2-week washout period, administer Ivonescimab 20 mg/kg in combination with the PC regimen (paclitaxel 135-175 mg/m² + carboplatin AUC 5) every 3 weeks.

Neoadjuvant therapy phase

Surgery PROCEDURE

Surgery

Neoadjuvant therapy phase

Ivonescimab DRUG

If MRD is positive and KRAS is negative, adjuvant therapy with Ivonescimab 20 mg/kg every 3 weeks should be administered until disease progression, unacceptable toxicity, withdrawal of informed consent, death, or termination due to other reasons, whichever occurs first.

Neoadjuvant therapy phase

Observation BEHAVIORAL

If MRD is negative, the patient should be placed under observation; once it turns positive, they will enter the corresponding treatment group as described above.

Neoadjuvant therapy phase

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age Range: Males or females aged 18 years or older.
• Diagnosis and Stage: Patients with histologically or cytologically confirmed resectable IB-IIIB NSCLC, staged according to the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology, 9th Edition.
• Informed Consent: Patients must voluntarily participate in the study, provide written informed consent, and be willing to comply with follow-up procedures.
• Prior Therapy: No prior systemic therapy for locally advanced or metastatic NSCLC (including adjuvant chemo/radiotherapy, neoadjuvant chemo/radiotherapy, definitive chemoradiotherapy, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, or anti-angiogenic therapy for locally advanced disease).
• Mutation Status: KRAS G12C mutation positivity must be confirmed by next-generation sequencing (NGS) or polymerase chain reaction (PCR) testing.
• Measurable Disease: At least one measurable target lesion as per RECIST v1.1. Lesions previously treated with radiotherapy or other local-regional therapies cannot be considered target lesions unless clear progression has been documented post-radiotherapy. At baseline, the lesion must be ≥10mm in the longest diameter (≥15mm in short axis for lymph nodes) on CT or MRI and be suitable for accurate repeated measurement per RECIST v1.1.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate Organ Function: Must meet the following criteria within 14 days prior to relevant tests, without transfusion or use of hematopoietic growth factors:
• Platelets (PLT) ≥90 × 10\^9/L
• Hemoglobin (HGB) ≥90 g/L
• Absolute Neutrophil Count (ANC) ≥1.5 × 10\^9/L
• Serum creatinine ≤1.5 × ULN or Creatinine Clearance (CrCl) ≥50 mL/min (calculated using the Cockcroft-Gault formula)
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if liver metastases are present)
• Total Bilirubin (TBIL) ≤1.5 × ULN (≤3 × ULN for patients with Gilbert's syndrome)
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN, or patients assessed by the investigator as having controlled bleeding tendency.

You may not qualify if:

• Prior Anti-Tumor Therapy:
• Previous receipt of any anti-tumor therapy for lung cancer (including adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, anti-angiogenic therapy, etc.).
• Treatment with any other investigational drug within 28 days prior to the first dose in this study.
• Treatment within 2 weeks prior to the first dose with NMPA-approved Chinese patent medicines explicitly indicated for anti-tumor purposes in their drug说明书 (e.g., Compound Banmao Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Yadanzi Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules, etc.).
• Recent Surgery: Any surgery within 4 weeks prior to screening examinations.
• Concurrent Primary Malignancy: Patients with a concurrent primary malignancy (except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, etc.).
• Abnormal Organ Function: Meeting any of the following at screening:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN).
• Creatinine clearance rate (CrCl) \> ULN.
• Hematological Abnormalities: Total white blood cell (WBC) count \> 10.0 × 10\^9/L or \< 1.0 × 10\^9/L at screening.
• Significant Comorbidities: History of immunodeficiency diseases (e.g., HIV), other active cancers or malignancy history, autoimmune diseases, severe cardiovascular or cerebrovascular diseases, or any other diseases that may significantly reduce life expectancy.
• Conditions Affecting Compliance: Any history of conditions that may affect protocol compliance (e.g., severe psychiatric disorders, cognitive dysfunction, drug abuse or addiction).
• Pregnancy, Lactation, and Contraception: Pregnant or lactating women, or subjects of childbearing potential unwilling or unable to use effective contraception.
• Allergy: Known allergy to any component of the study drug(s).
• Recent Trial Participation: Participation in any drug clinical trial within 6 months prior to screening.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Surgical Procedures, Operative; Observation

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Methods; Investigative Techniques

Central Study Contacts

Wen-Zhao Zhong, MD

CONTACT

86-13609777314; 13609777314@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 16, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share