Clinical trial NCT06394414: A Phase 1 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-01
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the AEs in YL201 combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors
timeFrame: Approximately within 36 months
measure: To determine the MTD/RED of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors
timeFrame: Approximately within 36 months
measure: To evaluate the efficacy of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR
timeFrame: Approximately within 36 months
measure: To determine the RP2D of YL201 in combination with serplulimab with or without platinum-based chemotherapy in advanced solid tumors based on ORR
timeFrame: Approximately within 36 months
Secondary outcomes:
measure: To evaluate the AUC of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the Cmax of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the Ctrough of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the CL of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the Vd of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the t1/2 of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the DpR of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the DCR of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the DoR of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the TTR of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the PFS of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the OS of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To evaluate the immunogenicity of YL201 combination therapy
timeFrame: Approximately within 36 months
measure: To assess the expression level of B7H3 and PD-L1 in Tumor tissue
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: beijinig
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Nanning
country: China
facility: Affiliated Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: Guangxi Zhuang Autonomous Region People's Hospital
state: Guangxi
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical College
state: Hainan
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Ha'erbin
country: China
facility: Cancer Hospital Affiliated to Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Provincial Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College HuaZhong University of Science Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changhua
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Provincial Cancer Hospital
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
city: Linyi
country: China
facility: Linyi Central Hospital
state: Shandong
city: Zaozhuang
country: China
facility: Zaozhuang Municipal Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Sichuan
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial Cancer Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
References: