A First-in-Human Study of YL217 in Patients With Advanced Solid Tumors

Official title

A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL217 in Patients With Advanced Solid Tumors

Overview

A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors

Detailed description

YL217 is an antibody-drug conjugate (ADC) that targets CDH17 (Cadherin-17) protein and is being developed for the treatment of cancer. YL217 is comprised of three components: 1) YL217-mAb, a CDH17-targeting recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody, 2) YL0010014, a topoisomerase I inhibitor, and 3) an enzymatically cleavable methylsulfonyl pyrimidine tripeptide drug linker.

The in vivo anti-tumor efficacy of YL217 was evaluated in immune-deficient mice bearing human colorectal cancer, gastric cancer and patient derived colorectal cancer xenograft tumors. The results indicated that YL217 was well tolerated, and YL217 suppressed growth of established human tumors in a dose-dependent manner in cancer cells or patient derived xenograft models.

Therefore, in order to meet the huge unmet medical needs in the field of gastrointestinal cancer treatment, it is planned to conduct the first human phase I clinical study of YL217 in patients with advanced solid tumors.

Interventions

• Drug YL217
  Patients will be treated with YL217 intravenous(IV)infusion.
• Drug YL217
  Patients will be treated with YL217 intravenous(IV)infusion.
• Drug YL217
  Patients will be treated with YL217 intravenous(IV)infusion.

Primary outcome measures

• Nature and frequency of dose-limiting toxicity(DLT) [Time frame: Up to approximately 3 years]
• Nature and frequency of adverse events (AEs) with severity [Time frame: Up to approximately 3 years]
• objective response rate (ORR) [Time frame: Up to approximately 3 years]

Secondary outcome measures (12)

• Eastern Cooperative Oncology Group performance status (ECOG PS) [Time frame: Up to approximately 3 years]
• To evaluate safety endpoint of peripheral oxygen saturation (SpO2) [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter AUC [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter Cmax [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter Ctrough [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter Tmax [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter CL [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter Vd [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics(PK) parameter t1/2 [Time frame: Up to approximately 3 years]
• Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs). [Time frame: Up to approximately 3 years]
• Disease control rate (DCR) [Time frame: Up to approximately 3 years]
• Duration of response (DoR) [Time frame: Up to approximately 3 years]

Eligibility criteria

Inclusion criteria

• Informed of the study before the start of the study and voluntarily sign their name and date in the ICF
• Able and willing to comply with protocol visits and procedures
• Age≥ 18 years
• ECOG PS of 0 or 1
• Tumor types as below:

For Part 1 and Part 2: Pathologically confirmed diagnosis of an advanced solid tumor.

For Part 3 (Histologically or cytologically confirmed diagnosis+ locally advanced unresectable or metastatic disease)

• Adequate organ and bone marrow function.
• Have at least 1 extracranial measurable tumor lesion.
• Adequate archival formalin-fixed paraffin embedded （FFPE） tissue from prior biopsy.

Exclusion criteria

• Prior treatment with an agent targeting CDH17
• Prior discontinuation of a topoisomerase I inhibitor due to treatment-related toxicities.
• Have received an ADC consisting of a topoisomerase I inhibitor.
• Concurrent enrollment in another clinical study, unless it is an observational clinical study.
• Inadequate washout period for prior anticancer treatment before the first dose of study drug
• Undergone major surgery within 4 weeks before the first dose of study drug or expect major surgery during the study.
• Received long term systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
• Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
• Diagnosis or evidence of spinal cord compression or leptomeningeal carcinomatosis.
• Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases.
• A history of non-infectious interstitial lung disease (ILD)/pneumonitis that requires steroids, current active ILD/pneumonitis.
• Have clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
• Uncontrolled third-space fluid that requires repeated drainage.
• Digestive system disease that may cause bleeding, perforation, jaundice, gastrointestinal obstruction.
• An active tuberculosis based on medical history.
• Known human immunodeficiency virus (HIV) infection.
• Active hepatitis C infection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 13 centers

• Mayo Clinic Arizona — Phoenix
• UCLA Hematology/Oncology - Santa Monica — Santa Monica
• Yale Cancer Center — New Haven
• The University of Kansas Cancer Center (KUCC) — Kansas City
• University of Maryland Medical Center-Greenebaum Cancer Ctr - Medical Oncology — Baltimore
• Karmanos Cancer Institute — Detroit
• Columbia University Irving Medical Center — New York
• Duke University Medical Center (DUMC) — Durham
• … and 5 more centers

China · 6 centers

• Peking Union Medical College Hospital — Beijing
• Harbin Medical University Cancer Hospital — Harbin
• Cancer Hospital of Shandong First Medical University — Jinan
• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai
• Tianjin Medical University Cancer Institute & Hospital — Tianjin
• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT06859762 · YL217-INT-101-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗