An Exploratory Phase II Clinical Study Protocol of Perioperative Treatment With Glesorasib Sequentially Combined With Ivonescimab and Chemotherapy for Resectable, Stage IB-IIIB, KRAS G12C-Mutant NSCLC
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 32
- Primary Endpoint
- Pathologic complete response (pCR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •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.
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Neoadjuvant therapy phase
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.
Intervention: Garsorasib (Drug)
Neoadjuvant therapy phase
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.
Intervention: Ivonescimab Combined With Chemotherapy (Drug)
Neoadjuvant therapy phase
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.
Intervention: Surgery (Procedure)
Neoadjuvant therapy phase
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.
Intervention: Ivonescimab (Drug)
Neoadjuvant therapy phase
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.
Intervention: Observation (Behavioral)
Outcomes
Primary Outcomes
Pathologic complete response (pCR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy
Time Frame: 14-24 weeks
Secondary Outcomes
- 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)
- One-year event-free survival rate (1-y EFS%)(12 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).)
- 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.)
- Overall Survival(60 months)
Investigators
Wen-zhao ZHONG
Principal Investigator
Guangdong Provincial People's Hospital