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.
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.
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.
Single group
Glecirasib
DrugFor Phase I Dose Escalation, Glecirasib includes 2 dose cohorts: 600 mg QD and 800 mg QD, respectively, to determine the Glecirasib PR2D dose for the Phase II study.
Ivonescimab
DrugAdministered intravenously at 20 mg/kg, every 3 weeks (Q3W).
Phase I: Maximum Tolerated Dose (MTD)
The MTD is determined using a standard 3+3 dose-escalation design. It is defined as the dose level prior to the dose at which ≥2 out of 3-6 patients experience a Dose-Limiting Toxicity (DLT) within the first 21 days of treatment
Phase I: Incidence of Dose-Limiting Toxicities (DLTs)
Evaluation of toxicities related to the study drugs, including hematologic and non-hematologic toxicities as defined in the protocol.
Phase I: Recommended Phase 2 Dose (RP2D)
The RP2D of Glecirasib in combination with Ivonescimab will be selected based on the comprehensive evaluation of the MTD, DLT occurrences, and overall safety data observed during the Phase I escalation phase. This dose will then be utilized in the Phase II Simon's two-stage expansion to further evaluate efficacy and safety.
Phase II: Objective Response Rate (ORR)
The proportion of patients who achieve a Complete Response (CR) or Partial Response (PR) based on RECIST v1.1.
Disease Control Rate (DCR)
Proportion of patients with CR, PR, or SD.
Progression-Free Survival (PFS)
Time from the first dose to the first documented disease progression or death from any cause.
Duration of Response (DOR)
Time from the first documented response (CR or PR) to progression or death.
Overall Survival (OS)
Time from the first dose to death from any cause
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
