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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: YL201

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing University Cancer Hospital
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Guangxi
    • Nanning, Guangxi, China
      • Affiliated Cancer Hospital of Guangxi Medical University
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital Tongji Medical College HuaZhong University of Science Technology
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Cancer Hospital
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital and Institute
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
    • Taizhou, Zhejiang, China
      • Taizhou Hospital of Zhejiang Province
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose escalation; YL201 in Combination with Serplulimab with or without Platinum-based Chemotherapy	Drug: YL201; 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.; Other Names: Platinum; Serplulimab
Experimental: Part2: Cohort Expansion; YL201 in Combination with Serplulimab with or without Platinum-based Chemotherapy	Drug: YL201; 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.; Other Names: Platinum; Serplulimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the AEs in YL201 combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors	AE: Adverse Event	Approximately within 36 months
To determine the MTD/RED of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors	maximum tolerated dose (MTD), recommended expansion dose (RED)	Approximately within 36 months
To evaluate the efficacy of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR	objective response rate (ORR)	Approximately within 36 months
To determine the RP2D of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR	recommended Phase 2 dose (RP2D)	Approximately within 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the AUC of YL201 combination therapy	area under the curve (AUC)	Approximately within 36 months
To evaluate the Cmax of YL201 combination therapy	peak concentration (Cmax)	Approximately within 36 months
To evaluate the Ctrough of YL201 combination therapy	trough concentration (Ctrough)	Approximately within 36 months
To evaluate the CL of YL201 combination therapy	clearance rate (CL)	Approximately within 36 months
To evaluate the Vd of YL201 combination therapy	volume of distribution (Vd)	Approximately within 36 months
To evaluate the t1/2 of YL201 combination therapy	half-life time (t1/2)	Approximately within 36 months
To evaluate the DpR of YL201 combination therapy	depth of response (DpR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Approximately within 36 months
To evaluate the DCR of YL201 combination therapy	disease control rate (DCR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Approximately within 36 months
To evaluate the DoR of YL201 combination therapy	duration of response (DoR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Approximately within 36 months
To evaluate the TTR of YL201 combination therapy	time to response (TTR); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Approximately within 36 months
To evaluate the PFS of YL201 combination therapy	progression-free survival (PFS); assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Approximately within 36 months
To evaluate the OS of YL201 combination therapy	Overall survival (OS)	Approximately within 36 months
To evaluate the immunogenicity of YL201 combination therapy	Incidence of anti-YL201 antibodies	Approximately within 36 months
To assess the expression level of B7H3 and PD-L1 in Tumor tissue		Approximately within 36 months

Collaborators and Investigators

• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2030

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 27, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 27, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: YL201-CN-102-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No