Trastuzumab Rezetecan(SHR-A1811) Combined With Ivonescimab (AK112) in Locally Advanced or Metastatic Non-small Cell Lung Cancer Harboring HER2 Gene Abnormalities

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.).

Age

18–75

Sex

ALL

Healthy volunteers

Not accepted

You may be eligible if

1. Absolute neutrophil count ≥ 1,500/mcL
2. Platelet count \> 90,000/mcL 19
3. Hemoglobin ≥ 9 g/dL (allow for blood transfusion)
4. Creatinine ≤ 1.5 × ULN
5. Total bilirubin ≤ 1.5 mg/dL or ≤ 26 μmol/L
6. If there is liver metastasis, AST (SGOT) / ALT (SGPT) ≤ 5 × ULN; if there is no liver metastasis, ≤ 2.5 × ULN
7. 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):
1. No hysterectomy or bilateral oophorectomy;
2. No natural menopause for at least 12 consecutive months (i.e., any time during the previous 12 months there was menstruation).

You may not be if

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.

What this study is about