This study is evaluating how safe, tolerable and effective the a new immunotherapy (IBI354) is in people with locally advanced inoperable or metastatic solid cancersA Phase 1/2, Multicenter, Open-label Study of IBI354 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors

Exclusion

1. Received previous anti-tumor therapy within 4 weeks or 5 half-lives of the anti-tumor regimens before the first administration of study drug, whichever is shorter;
2. Plan to receive other antitumor therapy during the study excluding palliative radiotherapy for the purpose of symptom (like pain) relief that must also do not have impact on tumor assessment throughout the study;
3. Potent cytochrome P450 3A4 (CYP3A4) inhibitors within 2 weeks or 5 half-lives (whichever is longer) before first administration of the study drug.
4. Has adverse reactions resulting from previous antitumor therapies, which have not resolved to Grade 0 or 1 toxicity according to NCI-CTCAE v5.0 (except for alopecia, fatigue, pigmentation and other conditions with no safety risk according to investigators' opinion) or baseline prior to first administration of the study drug;
5. Known symptomatic central nervous system (CNS) metastases.
6. History of pneumonia requiring corticosteroids therapy, or history of clinically significant lung diseases or who are suspected to have these diseases by imaging at screening period;

7. Uncontrolled diseases including:

   • Uncontrolled infection requiring systematic antibiotics, antivirals or antifungals within 2 weeks prior to first administration of the study drug;
   • Known human immunodeficiency virus (HIV) infection, or HIV positive (HIV 1/2 Ab positive);
   • HBsAg positive and/or HBcAb positive with HBV DNA titer ≥ 104 copies/mL or ≥ 2000 IU/mL or higher than lower limit of detection or HCV Ab positive with HCV RNA>103 copies/mL;
   • Active infection with COVID-19;
   • Active tuberculosis infection, or still on anti-tuberculosis therapy or received anti-tuberculosis therapy within 1 year prior to first administration of the study drug;
   • Active syphilis infection or latent syphilis requiring treatment;
   • Symptomatic congestive heart failure Grade II-IV, symptomatic or uncontrolled arrhythmias, QTc interval > 480 ms or personal or family history of congenital long/short QT syndrome;
   • SBP ≥ 160mmHg or DBP ≥ 100mmHg;
8. History of any arterial thromboembolic event within 6 months prior to the first administration of study drug, including myocardial infarction, unstable angina pectoris, cerebrovascular stroke or transient ischemic attack, etc.;
9. Risk of intestinal obstruction or perforation (including but not limited to: acute diverticulitis, abdominal abscess, etc.) or a history of inflammatory bowel disease, Crohn's disease, ulcerative colitis, or chronic diarrhea;

10. Do not have adequate treatment washout period before study drug administration, defined as:

    • Major surgery; ≥ 4 weeks.
    • Radiation therapy；≥ 4 weeks (if palliative stereotactic radiation therapy, ≥ 2 weeks).
    • Autologous transplantation；≥ 3 months.
    • Hormonal therapy；≥ 2 weeks.
    • Chemotherapy (including antibody drug therapy or other antitumor therapy)； ≥ 3 weeks.
    • Immunotherapy； ≥ 4 weeks.
    • Cytochrome P450 (CYP) 3A4 strong inhibitor；≥ 3 elimination half-lives of the inhibitor.