NSCLC Stage IVPhase 1/2NCT07339839
Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated NSCLC
A Phase 1/2 study testing Glecirasib and Ivonescimab in people with NSCLC Stage IV and KRAS G12C, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage IV, KRAS G12C
- What is being tested?
- Glecirasib and Ivonescimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2026to 30 Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
- Conditions
- NSCLC Stage IV, KRAS G12C
- Being tested
- Glecirasib, Ivonescimab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlecirasibDrug
Also called JAB-21822
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.
IvonescimabDrug
Also called AK112
Administered intravenously at 20 mg/kg, every 3 weeks (Q3W).
| Study group | Role | What they receive |
|---|---|---|
| Glecirasib Combined With Ivonescimab | Experimental | Not described Receives: Drug: Glecirasib; Drug: Ivonescimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Assessed up to 24 months
Secondary outcomes (5)
Disease Control Rate (DCR)
Proportion of patients with CR, PR, or SD.
Measured: Up to 24 months
Progression-Free Survival (PFS)
Time from the first dose to the first documented disease progression or death from any cause.
Measured: Up to 24 months
Duration of Response (DOR)
Time from the first documented response (CR or PR) to progression or death.
Measured: Up to 24 months
Overall Survival (OS)
Time from the first dose to death from any cause
Measured: Up to 24 months
Incidence of Adverse Events (AEs)
Severity of AEs graded by CTCAE v5.0
Measured: From first dose enrollment through 28 days after the last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start1 Mar 2026 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC Stage IVStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhijie Wang, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07339839
- Sponsor's protocol ID
- NCC5886
- Status last verified
- Jan 2026
- First submitted
- 5 Jan 2026
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07339839
- Acronym / sponsor ID
- NCC5886
- Conditions
- NSCLC Stage IV, KRAS G12C
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Mar 2026 (estimated)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 14 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glecirasib Combined With Ivonescimab | Experimental | Drug: Glecirasib, Drug: Ivonescimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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%.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlecirasibAlso: JAB-21822For 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. | Drug | Glecirasib Combined With Ivonescimab |
| IvonescimabAlso: AK112Administered intravenously at 20 mg/kg, every 3 weeks (Q3W). | Drug | Glecirasib Combined With Ivonescimab |
Primary outcome
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
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.
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.
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.
5 secondary outcomes
Disease Control Rate (DCR)
Time frame: Up to 24 months
Progression-Free Survival (PFS)
Time frame: Up to 24 months
Duration of Response (DOR)
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 24 months
Incidence of Adverse Events (AEs)
Time frame: From first dose enrollment through 28 days after the last dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glecirasib and Ivonescimab in people with NSCLC Stage IV and KRAS G12C, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhijie Wang, MD (010-67781331, wangzj@cicams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Maximum Tolerated Dose (MTD) (time frame: 21 days after the first dose.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.