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

NCT07339839 | Not Yet Recruiting Phase 1

• 1 other identifier: NCC5886
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

KRAS G12C; NSCLC Stage IV

Outcome Measures

Primary Outcomes (4)

• 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

  21 days after the first dose.

• 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.

  21 days after the first dose.

• 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.

  21 days after the first dose.

• 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.

  Assessed up to 24 months

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Incidence of Adverse Events (AEs)

  From first dose enrollment through 28 days after the last dose.

Study Arms (1)

Glecirasib Combined With Ivonescimab

EXPERIMENTAL

Drug: Glecirasib; Drug: Ivonescimab

Interventions

Ivonescimab DRUG

Administered intravenously at 20 mg/kg, every 3 weeks (Q3W).

Also known as: AK112

Glecirasib Combined With Ivonescimab

Glecirasib DRUG

For 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.

Also known as: JAB-21822

Glecirasib Combined With Ivonescimab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Zhijie Wang, MD

CONTACT

010-67781331; wangzj@cicams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 14, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2029
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share