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
Overview
- Phase
- Phase 1
- Intervention
- YL201
- Conditions
- Advanced Solid Tumors
- Sponsor
- MediLink Therapeutics (Suzhou) Co., Ltd.
- Enrollment
- 162
- Locations
- 30
- Primary Endpoint
- Evaluate the AEs in YL201 combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed of the study before the start of the study and voluntarily sign their name and date on the informed consent form (ICF).
- •Subjects will be enrolled in the dose-escalation phase: Advanced solid tumors, like NPC, SCLC and etc.
- •Subjects will be enrolled in the dose-expansion phase: NPC, SCLC, NSCLC and other advanced cancer.
- •According to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, there must be at least one extracranial measurable lesion.
- •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.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 by the United States of America standards.
- •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.
- •Subjects with expected survival ≥ 3 months. 10) Capable and willing to comply with the study protocol's scheduled visits and procedures.
Exclusion Criteria
- •Suitable for local radical treatment. 2) Previous Drug therapy targeting B7H
- •Previous Drug therapy with topoisomerase I inhibitors or ADCs composed of topoisomerase I inhibitors.
- •Prior treatment with anti-PD-(L)1, other immune checkpoint inhibitors, immune checkpoint agonists, or immunocellular therapies and other therapies targeting tumor immunity mechanisms.
- •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.
- •Underwent major surgery (excluding diagnostic surgery) or suffered serious trauma.
- •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.
- •Serious Infection prior to the first dose. 19) Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •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.
- •Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 3 days before the first dose.
- •Any illness, medical condition, organ system dysfunction, or social situation.
Arms & Interventions
Part 1: Dose escalation
YL201 in Combination with Serplulimab with or without Platinum-based Chemotherapy
Intervention: YL201
Part2: Cohort Expansion
YL201 in Combination with Serplulimab with or without Platinum-based Chemotherapy
Intervention: YL201
Outcomes
Primary Outcomes
Evaluate the AEs in YL201 combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors
Time Frame: Approximately within 36 months
AE: Adverse Event
To determine the MTD/RED of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors
Time Frame: Approximately within 36 months
maximum tolerated dose (MTD), recommended expansion dose (RED)
To evaluate the efficacy of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR
Time Frame: Approximately within 36 months
objective response rate (ORR)
To determine the RP2D of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR
Time Frame: Approximately within 36 months
recommended Phase 2 dose (RP2D)
Secondary Outcomes
- To evaluate the CL of YL201 combination therapy(Approximately within 36 months)
- To evaluate the t1/2 of YL201 combination therapy(Approximately within 36 months)
- To evaluate the TTR of YL201 combination therapy(Approximately within 36 months)
- To evaluate the Vd of YL201 combination therapy(Approximately within 36 months)
- To evaluate the DpR of YL201 combination therapy(Approximately within 36 months)
- To assess the expression level of B7H3 and PD-L1 in Tumor tissue(Approximately within 36 months)
- To evaluate the AUC of YL201 combination therapy(Approximately within 36 months)
- To evaluate the Cmax of YL201 combination therapy(Approximately within 36 months)
- To evaluate the Ctrough of YL201 combination therapy(Approximately within 36 months)
- To evaluate the DoR of YL201 combination therapy(Approximately within 36 months)
- To evaluate the DCR of YL201 combination therapy(Approximately within 36 months)
- To evaluate the PFS of YL201 combination therapy(Approximately within 36 months)
- To evaluate the immunogenicity of YL201 combination therapy(Approximately within 36 months)
- To evaluate the OS of YL201 combination therapy(Approximately within 36 months)