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

MediLink Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: YL217

Study type: Interventional

Funder types: Industry

Identifiers

NCT06859762

YL217-INT-101-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed of the study before the start of the study and voluntarily sign their name and date in the informed consent form (ICF)
• Able and willing to comply with protocol visits and procedures
• Aged ≥ 18 years
• Eastern Cooperative Oncology Group performance status (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 a topoisomerase I inhibitor within protocol defined time before the first dose of study drug.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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220 participants in 3 patient groups

Part 2: The backfill stage of YL217

Experimental group

Description:

Patients will be enrolled at one or more dose levels that do not exceed the dose that is deemed safe and tolerable in dose escalation. Then several dose levels will be selected as the recommended dose for expansion (RDE).

Treatment:

Drug: YL217

Drug: YL217

Drug: YL217

Part 1: Dose-Escalation Part

Experimental group

Description:

Participants will receive escalating doses of YL217 until doses for optimization are determined

Treatment:

Drug: YL217

Drug: YL217

Drug: YL217

Part 3: Dose-Expansion Part

Experimental group

Description:

Upon completion of Part 1 and Part 2 with determination of MTD/RDE(s), the dose-expansion part will be conducted to further support the RP2D selection.

Treatment:

Drug: YL217

Drug: YL217

Drug: YL217