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

January 5, 2026 updated by: Zhijie Wang, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Prospective, Multi-center, Phase I/II Clinical Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Glecirasib Combined With Ivonescimab
Drug: Glecirasib
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.
Other Names:
  • JAB-21822
Drug: Ivonescimab
Administered intravenously at 20 mg/kg, every 3 weeks (Q3W).
Other Names:
  • AK112

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase I: Maximum Tolerated Dose (MTD)
Time Frame: 21 days after the first dose.
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)
Time Frame: 21 days after the first dose.
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)
Time Frame: 21 days after the first dose.
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)
Time Frame: Assessed up to 24 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: Up to 24 months
Proportion of patients with CR, PR, or SD.
Up to 24 months
Progression-Free Survival (PFS)
Time Frame: Up to 24 months
Time from the first dose to the first documented disease progression or death from any cause.
Up to 24 months
Duration of Response (DOR)
Time Frame: Up to 24 months
Time from the first documented response (CR or PR) to progression or death.
Up to 24 months
Overall Survival (OS)
Time Frame: Up to 24 months
Time from the first dose to death from any cause
Up to 24 months
Incidence of Adverse Events (AEs)
Time Frame: From first dose enrollment through 28 days after the last dose.
Severity of AEs graded by CTCAE v5.0
From first dose enrollment through 28 days after the last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCC5886

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings