Non Small Cell Lung CancerPhase 2NCT07630077
Trastuzumab Rezetecan(SHR-A1811) Combined With Ivonescimab (AK112) in Locally Advanced or Metastatic Non-small Cell Lung Cancer Harboring HER2 Gene Abnormalities
A Phase 2 study testing Trastuzumab Rezetecan and ivonescimab in people with Non Small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a phase II trial in patients with locally advanced or metastatic non-small cell lung cancer harboring HER2 gene abnormalities （amplification or overexpression）with a performance status of 0 to1 who are planned to receive first-line treatment or who have falied the first-line treatment Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Trastuzumab Rezetecan and ivonescimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2026to 1 Jul 2028
- Phase
- Phase 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. The subjects voluntarily participated in this study and signed the informed consent form, showing good compliance; 2. Age: 18 - 75 years old (at the time of signing the informed consent form); 3. ECOG PS score: 0 - 1 point; 4. Expected survival period: more than 3 months; 5. According to the International Association for the Study of Lung Cancer and the 8th edition of the American Joint Committee on Cancer's Lung Cancer TNM staging system, patients with locally advanced (stage IIIB/III C), metastatic or recurrent (stage IV) NSCLC that cannot be treated surgically and cannot receive radical concurrent radiotherapy and chemotherapy, and whose cancer is confirmed by cytology or histology, are eligible for this study. (Note: Mixed tumors will be classified according to the main cell type; if there is a small cell component, the subject does not meet the inclusion criteria); 6. Cohort 1: Previous first-line treatment failed, and HER2 amplification or overexpression (2+ or 3+) is required; Cohort 2: Patients who received no systematic treatment at the initial diagnosis, with HER2 amplification or overexpression (2+ or 3+), and with PD-L1 ≥ 1%; 7. At least one measurable lesion must be present according to the RECIST 1.1 standard. Lesions that have received radiotherapy cannot be regarded as target lesions unless there is a clear progression after radiotherapy; 8. Patients must have adequate organ and bone marrow functions, defined as follows:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count > 90,000/mcL 19
- Hemoglobin ≥ 9 g/dL (allow for blood transfusion)
- Creatinine ≤ 1.5 × ULN
- Total bilirubin ≤ 1.5 mg/dL or ≤ 26 μmol/L
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- If there is liver metastasis, AST (SGOT) / ALT (SGPT) ≤ 5 × ULN; if there is no liver metastasis, ≤ 2.5 × ULN
- Albumin ≥ 2.5 g/dL 9. Both the reproductive-aged women and their male partners must agree to take adequate contraceptive measures (hormonal or barrier methods; abstinence) before entering the study, during the study, and within 90 days after completing the study (hormonal or barrier methods; abstinence). If a woman becomes pregnant during the study or suspects she is pregnant, she should immediately inform the attending physician.
- Note: Reproductive-aged women are any women who meet the following criteria (regardless of sexual orientation, whether they have undergone tubal ligation or chosen to remain single):
- No hysterectomy or bilateral oophorectomy;
- No natural menopause for at least 12 consecutive months (i.e., any time during the previous 12 months there was menstruation).
Who cannot join
- 1. Have previously received treatment with anti-HER2 drugs, including large molecule antibodies, TKIs, ADCs, etc.; 2. Have a history of interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis after using steroids, or have active non-infectious pneumonia with interstitial lung changes during the screening period, active pulmonary tuberculosis, pneumoconiosis, or having ≥2 grade other types of pneumonia, or severe impairment of lung function (FEV1 or DLCO or DLCO/VA as a percentage of the predicted value is less than 40%) confirmed by lung function tests, etc.; 3. Have experienced arterial/deep vein thrombosis events within 6 months before treatment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, etc.; 4. Have ≥2 grade myocardial ischemia or myocardial infarction, arrhythmias (including QTcF ≥ 450ms (male), QTcF ≥ 470ms (female), and ≥2 grade congestive heart failure (New York Heart Association (NYHA) classification), left ventricular ejection fraction (LVEF) < 50%; angina pectoris requiring anti-myocardial ischemia drugs; clinically significant heart valve disease); 5. Have active autoimmune diseases or autoimmune disease history, including but not limited to Crohn's disease, ulcerative colitis, autoimmune hepatitis/enteritis/vasculitis/renalitis, etc., except for the following situations: ① Controllable type I diabetes; ② Hypothyroidism controlled by hormone replacement therapy; ③ Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis); ④ Other diseases that are expected not to recur (such as asthma that has been cured in childhood); 6. Need systemic or local use of immunosuppressants to achieve the purpose of immunosuppression and still need to continue using them within 2 weeks before randomization; 7. Have pleural effusion (thoracic cavity, abdominal cavity or pericardial cavity) with repeated drainage to relieve clinical symptoms (judged by the investigator), or have received pleural effusion drainage for therapeutic purposes within 2 weeks before treatment; 8. Have symptomatic or progressive CNS metastasis or cancerous meningitis, with diffuse dissemination; Have a history of brain metastasis and if the subject is clinically stable, can be considered for inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Department of Medical Oncology,Cancer Center of Sun Yat-Sen University
Guangzhou, Guangdong, 510060
Li Zhang, MD, 86-20-87343458, zhangli@sysucc.org.cn
About this study
Official title: Evaluation of the Efficacy and Safety of Trastuzumab Rezetecan(SHR-A1811) Combined With Ivonescimab (AK112) in Locally Advanced or Metastatic Non-small Cell Lung Cancer With HER2 Gene Abnormalities in a Phase II Clinical Trial
This is a phase II trial in patients with locally advanced or metastatic non-small cell lung cancer harboring HER2 gene abnormalities （amplification or overexpression）with a performance status of 0 to1 who are planned to receive first-line treatment or who have falied the first-line treatment
Read the detailed description
This is a Phase II study aimed at evaluating the efficacy and safety of Trastuzumab Rezetecan (SHR-A1811) combined with ivonescimab (AK112) in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 gene abnormalities (amplification or overexpression). The study was divided into two cohorts: Cohort 1 included patients with HER2 amplification or overexpression who had failed first-line treatment; Cohort 2 included patients with HER2 amplification or overexpression who were diagnosed for the first time and had PD-L1 expression ≥ 1%. All eligible patients received intravenous administration of SHR-A1811 at 4.8 mg/kg combined with AK112 at 20 mg/kg, once every 3 weeks. The primary endpoint was the progression-free survival (PFS) evaluated by the investigators according to RECIST v1.1; secondary endpoints included duration of response (DOR), objective response rate (ORR), overall survival (OS), and safety indicators (adverse events, serious adverse events, etc.).
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Trastuzumab Rezetecan, ivonescimab
- Keywords
- HER2 gene abnormalities (amplification or overexpression)
- 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.
Trastuzumab RezetecanDrug
4.8 mg/kg Intravenous injection until disease progression
ivonescimabDrug
20 mg/kg Intravenous injection until disease progression
| Study group | Role | What they receive |
|---|---|---|
| cohort 2 | Experimental | patients with HER2 amplification or overexpression who were diagnosed for the first time and had PD-L1 expression ≥ 1% Receives: Drug: Trastuzumab Rezetecan; Drug: ivonescimab |
| cohort 1 | Experimental | patients with HER2 amplification or overexpression who had failed first-line treatment Receives: Drug: Trastuzumab Rezetecan; Drug: ivonescimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
The time from the first treatment to disease progression or death due to any cause (whichever occurs first)
Measured: assessed up to 36 months
Secondary outcomes (4)
Duration of Response
The time from the first assessment of the tumor as being in an objective remission (PR or CR) to the first assessment of disease progression (PD) or death due to any cause prior to PD;
Measured: up to 36 months
Objective Response Rate
The proportion of patients with the best overall therapeutic effect of CR and PR
Measured: up to 36 months
Overall survival
The time from the first trial treatment to death due to any cause
Measured: up to 60 months
Incidence and severity of adverse events (AEs)
Overall incidence of AEs; the incidence of grade 3 or above AEs; the incidence of severe adverse events (SAE); the incidence of drug-related AEs; the incidence of AEs resulting in permanent withdrawal of drugs; the incidence of AEs leading to dose adjustment
Measured: through study completion, an average of 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start1 Jul 2026 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Zhang, MD, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07630077
- Sponsor's protocol ID
- B2025-730-01
- Status last verified
- Jun 2026
- First submitted
- 1 Jun 2026
- Last updated
- 5 Jun 2026
- Results posted
- 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 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy and Safety of Trastuzumab Rezetecan(SHR-A1811) Combined With Ivonescimab (AK112) in Locally Advanced or Metastatic Non-small Cell Lung Cancer With HER2 Gene Abnormalities in a Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT07630077
- Acronym / sponsor ID
- B2025-730-01
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- HER2 gene abnormalities (amplification or overexpression)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 5 Jun 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 is a phase II trial in patients with locally advanced or metastatic non-small cell lung cancer harboring HER2 gene abnormalities （amplification or overexpression）with a performance status of 0 to1 who are planned to receive first-line treatment or who have falied the first-line treatment
Detailed description
This is a Phase II study aimed at evaluating the efficacy and safety of Trastuzumab Rezetecan (SHR-A1811) combined with ivonescimab (AK112) in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 gene abnormalities (amplification or overexpression). The study was divided into two cohorts: Cohort 1 included patients with HER2 amplification or overexpression who had failed first-line treatment; Cohort 2 included patients with HER2 amplification or overexpression who were diagnosed for the first time and had PD-L1 expression ≥ 1%. All eligible patients received intravenous administration of SHR-A1811 at 4.8 mg/kg combined with AK112 at 20 mg/kg, once every 3 weeks. The primary endpoint was the progression-free survival (PFS) evaluated by the investigators according to RECIST v1.1; secondary endpoints included duration of response (DOR), objective response rate (ORR), overall survival (OS), and safety indicators (adverse events, serious adverse events, etc.).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cohort 2 | Experimental | Drug: Trastuzumab Rezetecan, Drug: ivonescimabpatients with HER2 amplification or overexpression who were diagnosed for the first time and had PD-L1 expression ≥ 1% |
| cohort 1 | Experimental | Drug: Trastuzumab Rezetecan, Drug: ivonescimabpatients with HER2 amplification or overexpression who had failed first-line treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. The subjects voluntarily participated in this study and signed the informed consent form, showing good compliance; 2. Age: 18 - 75 years old (at the time of signing the informed consent form); 3. ECOG PS score: 0 - 1 point; 4. Expected survival period: more than 3 months; 5. According to the International Association for the Study of Lung Cancer and the 8th edition of the American Joint Committee on Cancer's Lung Cancer TNM staging system, patients with locally advanced (stage IIIB/III C), metastatic or recurrent (stage IV) NSCLC that cannot be treated surgically and cannot receive radical concurrent radiotherapy and chemotherapy, and whose cancer is confirmed by cytology or histology, are eligible for this study. (Note: Mixed tumors will be classified according to the main cell type; if there is a small cell component, the subject does not meet the inclusion criteria); 6. Cohort 1: Previous first-line treatment failed, and HER2 amplification or overexpression (2+ or 3+) is required; Cohort 2: Patients who received no systematic treatment at the initial diagnosis, with HER2 amplification or overexpression (2+ or 3+), and with PD-L1 ≥ 1%; 7. At least one measurable lesion must be present according to the RECIST 1.1 standard. Lesions that have received radiotherapy cannot be regarded as target lesions unless there is a clear progression after radiotherapy; 8. Patients must have adequate organ and bone marrow functions, defined as follows:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count > 90,000/mcL 19
- Hemoglobin ≥ 9 g/dL (allow for blood transfusion)
- Creatinine ≤ 1.5 × ULN
Key exclusion criteria (1 listed)
- 1. Have previously received treatment with anti-HER2 drugs, including large molecule antibodies, TKIs, ADCs, etc.; 2. Have a history of interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis after using steroids, or have active non-infectious pneumonia with interstitial lung changes during the screening period, active pulmonary tuberculosis, pneumoconiosis, or having ≥2 grade other types of pneumonia, or severe impairment of lung function (FEV1 or DLCO or DLCO/VA as a percentage of the predicted value is less than 40%) confirmed by lung function tests, etc.; 3. Have experienced arterial/deep vein thrombosis events within 6 months before treatment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, etc.; 4. Have ≥2 grade myocardial ischemia or myocardial infarction, arrhythmias (including QTcF ≥ 450ms (male), QTcF ≥ 470ms (female), and ≥2 grade congestive heart failure (New York Heart Association (NYHA) classification), left ventricular ejection fraction (LVEF) < 50%; angina pectoris requiring anti-myocardial ischemia drugs; clinically significant heart valve disease); 5. Have active autoimmune diseases or autoimmune disease history, including but not limited to Crohn's disease, ulcerative colitis, autoimmune hepatitis/enteritis/vasculitis/renalitis, etc., except for the following situations: ① Controllable type I diabetes; ② Hypothyroidism controlled by hormone replacement therapy; ③ Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis); ④ Other diseases that are expected not to recur (such as asthma that has been cured in childhood); 6. Need systemic or local use of immunosuppressants to achieve the purpose of immunosuppression and still need to continue using them within 2 weeks before randomization; 7. Have pleural effusion (thoracic cavity, abdominal cavity or pericardial cavity) with repeated drainage to relieve clinical symptoms (judged by the investigator), or have received pleural effusion drainage for therapeutic purposes within 2 weeks before treatment; 8. Have symptomatic or progressive CNS metastasis or cancerous meningitis, with diffuse dissemination; Have a history of brain metastasis and if the subject is clinically stable, can be considered for inclusion.
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 |
|---|---|---|
| Trastuzumab Rezetecan4.8 mg/kg Intravenous injection until disease progression | Drug | cohort 1, cohort 2 |
| ivonescimab20 mg/kg Intravenous injection until disease progression | Drug | cohort 1, cohort 2 |
Primary outcome
Progression free survival
Time frame: assessed up to 36 months
The time from the first treatment to disease progression or death due to any cause (whichever occurs first)
4 secondary outcomes
Duration of Response
Time frame: up to 36 months
Objective Response Rate
Time frame: up to 36 months
Overall survival
Time frame: up to 60 months
Incidence and severity of adverse events (AEs)
Time frame: through study completion, an average of 60 months
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 5 Jun 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.
Department of Medical Oncology,Cancer Center of Sun Yat-Sen University
Guangzhou, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab Rezetecan and ivonescimab in people with Non Small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.
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 11 inclusion and 1 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 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: assessed up to 36 months). 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 5 Jun 2026.