Advanced Solid Tumors
Conditions
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.
Interventions
DRUGYL201
YL201 (High dose, medium dose and low dose; Q3W) in Combination with Serplulimab (4.5mg/kg; Q3W) with or without Platinum(70 mg/m2; Q3W)-based Chemotherapy.
Sponsors
MediLink Therapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the AEs in YL201 combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors | 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 | 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 | 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 | Approximately within 36 months | recommended Phase 2 dose (RP2D) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the t1/2 of YL201 combination therapy | Approximately within 36 months | half-life time (t1/2) |
| To evaluate the AUC of YL201 combination therapy | Approximately within 36 months | area under the curve (AUC) |
| To evaluate the DpR of YL201 combination therapy | Approximately within 36 months | depth of response (DpR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| To evaluate the DCR of YL201 combination therapy | Approximately within 36 months | disease control rate (DCR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| To evaluate the DoR of YL201 combination therapy | Approximately within 36 months | duration of response (DoR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| To evaluate the Cmax of YL201 combination therapy | Approximately within 36 months | peak concentration (Cmax) |
| To evaluate the PFS of YL201 combination therapy | Approximately within 36 months | progression-free survival (PFS); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| To evaluate the OS of YL201 combination therapy | Approximately within 36 months | Overall survival (OS) |
| To evaluate the immunogenicity of YL201 combination therapy | Approximately within 36 months | Incidence of anti-YL201 antibodies |
| To assess the expression level of B7H3 and PD-L1 in Tumor tissue | Approximately within 36 months | — |
| To evaluate the TTR of YL201 combination therapy | Approximately within 36 months | time to response (TTR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| To evaluate the Ctrough of YL201 combination therapy | Approximately within 36 months | trough concentration (Ctrough) |
| To evaluate the CL of YL201 combination therapy | Approximately within 36 months | clearance rate (CL) |
| To evaluate the Vd of YL201 combination therapy | Approximately within 36 months | volume of distribution (Vd) |
Countries
China
Outcome results
None listed