Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated NSCLC

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase

Begins enrollment this month

Phase 2

Phase 1

Conditions

NSCLC Stage IV

KRAS G12C

Treatments

Drug: Ivonescimab

Drug: Glecirasib

Study type

Interventional

Funder types

Other

Identifiers

NCT07339839

NCC5886

Details and patient eligibility

About

This study evaluates the safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) of Glecirasib in combination with Ivonescimab in patients with previously untreated, KRAS G12C-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥1%. The study includes a Phase I 3+3 dose-escalation stage followed by a Phase II Simon two-stage design to assess preliminary antitumor efficacy.

Enrollment

42 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed written informed consent.
Age ≥18 years.
Newly diagnosed, unresectable, locally advanced (ineligible for curative concurrent - chemoradiotherapy) or metastatic NSCLC per AJCC 9th edition.
KRAS G12C mutation confirmed by validated testing.
PD-L1 TPS ≥1%.
≥1 measurable lesion per RECIST v1.1.
No prior systemic therapy for advanced/metastatic NSCLC; prior adjuvant therapy allowed if completed >6 months before dosing and toxicities recovered to ≤Grade 1.
ECOG PS 0-2.
Life expectancy >3 months
Adequate organ function (hematologic, hepatic, renal, coagulation per protocol thresholds)
Negative pregnancy test for women of childbearing potential; adequate contraception for men and women through 3 months post-treatment
Willing and able to comply with study procedures and follow-up.

Exclusion criteria

History of other malignancies (exceptions: cured basal cell carcinoma, cervical carcinoma in situ)
Predominant squamous NSCLC, small cell carcinoma, or neuroendocrine carcinoma.
Other actionable drivers (EGFR, ALK, ROS1, RET, BRAF, NTRK, MET, etc.).
Known hypersensitivity to study drugs.
Prior PD-1/PD-L1 inhibitors or KRAS inhibitors.
Active autoimmune disease or autoimmune disease history requiring systemic therapy.
Systemic immunosuppressive therapy within 14 days prior to first dose.
Symptomatic ascites/pleural effusion needing recurrent drainage.
Significant cardiovascular disease (NYHA ≥2, MI within 1 year, uncontrolled arrhythmias).
Active infection, unexplained fever >38.5°C.
Interstitial lung disease or pneumonitis.
HIV infection or other immunodeficiency.
Live vaccines within 4 weeks.
Substance abuse, alcoholism, or psychiatric disorders impairing compliance.
Unable to swallow oral medication.
Any condition that may interfere with study participation or interpretation as judged by investigator.