A Phase 1 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Advanced Solid Tumors

A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Combination With Serplulimab With or Without Platinum-based Chemotherapy in Selected Subjects With Advanced Solid Tumors

This is a phase 1, multicenter, open-label stydy to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Combination with Serplulimab with or without Platinum-based Chemotherapy in Selected Subjects with Advanced Solid Tumors conducted in China. The study will include 2 parts: a dose escalation part (Part 1) followed by a cohort expansion part (Part 2).

Part 1 will estimate the safety, tolerability and MTD/RED(s) of YL201 in combination with serplulimab with or without platinum-based chemotherapy in selected subjects with advanced solid tumors.

Part 2 will estimate the efficacy of YL201 in combination with serplulimab with or without platinum-based chemotherapy in selected subjects with advanced solid tumors.

Inclusion Criteria:

• 1) Informed of the study before the start of the study and voluntarily sign their name and date on the informed consent form (ICF).

  2) Subjects will be enrolled in the dose-escalation phase: Advanced solid tumors, like NPC, SCLC and etc.

  3) Subjects will be enrolled in the dose-expansion phase: NPC, SCLC, NSCLC and other advanced cancer.

  4) According to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, there must be at least one extracranial measurable lesion.

  5) Archived or fresh tumor tissue samples can be provided. 6) Within 7 days before the first dose, organ and bone marrow functions must meet the requirements.

  7) Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 by the United States of America standards.

  8) Female subjects of childbearing potential must agree to use highly effective contraception measures from screening throughout the duration of the study and for at least 6 months after the last dose of the study drug. Male subjects must agree to use highly effective contraception measures from screening throughout the duration of the study and for at least 6 months after the last dose of the study drug.

  9) Subjects with expected survival ≥ 3 months. 10) Capable and willing to comply with the study protocol's scheduled visits and procedures.

Exclusion Criteria:

• 1) Suitable for local radical treatment. 2) Previous Drug therapy targeting B7H3. 3) Previous Drug therapy with topoisomerase I inhibitors or ADCs composed of topoisomerase I inhibitors.

  4) Prior treatment with anti-PD-(L)1, other immune checkpoint inhibitors, immune checkpoint agonists, or immunocellular therapies and other therapies targeting tumor immunity mechanisms.

  5) Toxicity from previous anticancer treatments has not resolved. 6) Concurrent enrollment in another clinical study. 7) Inadequate washout period for prior anticancer treatment before the first dose of study drug.

  8) Underwent major surgery (excluding diagnostic surgery) or suffered serious trauma.

  9) Received allogeneic stem cell or solid organ transplant. 10) Active autoimmune diseases requiring systemic treatment. 11) Received systemic steroids. 12) Metastases to meninges or carcinomatous meningitis. 13) Brain metastasis or spinal cord compression. 14) Uncontrolled or clinically significant cardiovascular disease. 15) Clinically significant concomitant pulmonary disease. 16) With uncontrolled third-space fluid. 17) History of gastrointestinal perforation and / or fistula within 6 months prior to the first dose.

  18) Serious Infection prior to the first dose. 19) Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

  20) Any other primary malignancy before the first dose of study drug. 21) A history of severe hypersensitivity reactions to the investigational product, inactive ingredients in the formulation, or other monoclonal antibodies.

  22) Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 3 days before the first dose.

  23) Any illness, medical condition, organ system dysfunction, or social situation.