A Phase I Study of SIM0505 in Participants With Advanced Solid Tumors

Exclusion Criteria15

• For Part 2: has clear cell, mucinous or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer; mixed nonsmall cell and small cell carcinoma, or adenosquamous cell lung cancer with an adenocarcinoma component <50% (the participant is eligible if the adenocarcinoma component is ≥50%).
• Any other malignancy within 2 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence.
• Participant has symptomatic central nervous system (CNS) metastases, or CNS metastases requiring CNS-directed local therapy (such as radiotherapy or surgery) or corticosteroids therapy within 2 weeks of first dose of study treatment.
• History of bowel obstruction within 3 months prior to the first dose of study treatment.
• Known psychiatric disorder or drug abuse that would interfere the study requirements.
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
• Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
• History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.
• Prior exposure to other CDH6-targeted agents or an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000).
• \. Major surgery within 2 weeks of receiving the first dose of study treatment.
• \. Has received prior anti-cancer therapies within the following time frames prior to the first dose of study treatment; Previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks, Anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study treatment, Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks and/or Radiation therapy <4 weeks.
• \. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
• \. Administration of below medications≤14 days prior to the first dose of SIM0505; Strong and moderate CYP3A4 inhibitors and Drugs with known risk of Torsades de Pointes (TdP).
• \. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
• \. Active hepatitis B or hepatitis C infection 18. Participants with clinically significant cardiovascular diseases. 19. History of allogeneic organ transplantation or graft-versus-host disease. 20. Known hypersensitivity to study drug or any of the excipients. 21. Participant is pregnant or breastfeeding. 22. Other conditions that researchers consider inappropriate for inclusion.