A Multicenter, Single-arm, Open-label Study Evaluating the Safety and Efficacy of AK112 Combined With Chemotherapy as First-line Treatment for Non-squamous NSCLC Patients With BRAIN Metastases and Negative Driver Genes (IVO BRAIN)

Exclusion Criteria

• •2: any active infection requiring systemic anti-infective therapy within 14 days before the first dose
• •3\) myocardial infarction with uncontrolled arrhythmia (including QTc interval ≥450 ms in men and ≥470 ms in women) within 6 months before the first dose (QTc interval was calculated with Fridericia's formula)
• •4: Or grade III-IV cardiac dysfunction according to the New York Heart Association (NYHA) standard or left ventricular ejection fraction \<50% by echocardiography
• •5\) subjects with ≥ grade 2 CTCAE peripheral neuropathy
• •6\) subjects had uncontrolled or symptomatic hypercalcemia (\>1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN)
• •7\) subjects with previous or screening history of interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severely impaired pulmonary function, which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity according to the investigator's judgment
• •8\) untreated active hepatitis B subjects (HBsag-positive and HBV-DNA \> 1000 copies /mL (200 IU/mL) or higher than the lower limit of detection, whichever is higher) and, for those with hepatitis B, required to receive anti-HBV treatment for the duration of the study treatment
• •9: Active hepatitis C subjects (positive for HCV antibodies and HCV-RNA levels above the lower limit of detection)
• •10: Or patients with known active syphilis infection (excluding patients with positive heterologous antibody test, negative non-heterologous antibody test and inactive infection confirmed by clinical judgment)
• •11 Or a known history of human immunodeficiency virus (HIV) positivity or screening positive for HIV
• •12\) the subject has a known active or suspected autoimmune disease. Subjects who were in a stable state and did not require systemic immunosuppressive therapy were allowed to enroll.
• •13\) patients with other active malignant tumors within 5 years or at the same time. Localized tumors that had been cured for more than 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, and breast cancer in situ, were eligible for inclusion.
• •14\) Recipients of a live or attenuated vaccine within 28 days before the first dose, or having a plan to receive such vaccine during the study period. However, inactivated virus vaccines for seasonal influenza are permitted
• •15\) radical radiotherapy or whole brain radiotherapy (WBRT) to the skull within 3 months before the first dose
• •16\) subjects with spinal cord compression that could not be cured by surgery and/or radiotherapy
• •17\) patients with deep vein thrombosis, current anticoagulant or platelet therapy, or previous use of antiangiogenic drugs for deep vein thrombosis or severe bleeding
• •18\) poorly controlled (poorly controlled defined as BP ≥160/100 MMHG despite optimal hypertension treatment)
• •19\) had undergone major surgery within 28 days before the first dose (major surgery was defined for this study as a procedure requiring at least 3 weeks of recovery before being able to undergo study treatment)
• •20\) who are participating in another clinical study, or who have participated in any other clinical trial (including drugs, devices, etc.) and received intervention within 3 months before screening or within 5 half-lives (whichever is longer)
• •21\) candidates for or prior recipients of organ or bone marrow transplantation
• •22\) subjects had a known history of psychotropic drug abuse or drug use
• •23\) subjects with any factors considered by the investigator to be ineligible for the trial.
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