Overview

This is a Phase 1a/b, multicenter, open-label, first-in-human, dose escalation, expansion and extension study to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and preliminary efficacy of IBI343 (study drug) in participants with locally advanced unresectable or metastatic solid tumors.

Eligibility

Inclusion Criteria:

1. Male or female subjects, age ≥ 18 years.
2. Phase 1a Dose Escalation: Subjects with a documented (histologically- or cytologically-proven) locally advanced unresectable or metastatic solid tumor malignancy for which standard treatment does not exist, is no longer effective, or is not acceptable to the subject.

   Phase 1a Dose Expansion and Phase 1b Dose Extension: Subjects with pathologically documented locally advanced unresectable or metastatic gastric/gastro-esophageal junction adenocarcinoma or pancreatic ductal adenocarcinoma with Claudin 18.2 expression.

3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
4. Adequate bone marrow and organ function.
5. Subjects both male and female, who are either not of childbearing potential or who agree to use two highly effective method of contraception during the study (begin from screening or within 2 weeks prior to the first dose, whichever comes first, and continue until 6 months after the last dose of study drug.

Exclusion Criteria:

1. Subjects with a pathologically documented lung cancer.
2. Subjects 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 greater.
3. Subjects 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.
4. Potent cytochrome P450 3A4 (CYP3A4) and/or P450 1A2 (CYP1A2) inhibitors within 2 weeks or 5 half-lives (whichever is longer) before first administration of the study drug.
5. 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.
6. Known symptomatic central nervous system (CNS) metastases.
7. 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
8. Uncontrolled diseases including:
   • Uncontrolled infection requiring systematic antibiotics, antivirals or antifungals within 4 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 ≥ 10^4 copies/mL or ≥2000 IU/mL or higher than lower limit of detection)
   • HCV Ab positive with HCV RNA>10^3 copies/mL).
   • Active syphilis infection or latent syphilis requiring treatment;
   • QTc interval > 480 ms
   • SBP≥160mmHg or DBP≥100mmHg
9. History of any arterial thromboembolic event within 6 months prior to the first

   administration of study drug, including myocardial infarction, unstable angina pectoris, pulmonary embolism, cerebrovascular stroke or transient ischemic attack, etc

10. Risk of intestinal obstruction or perforation (including but not limited to: acute diverticulitis, abdominal abscess, or a history of abdominal cancer) or a history of inflammatory bowel disease or extensive bowel resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.