Clinical trial NCT06859762: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-03-05
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Phase 1, Multicenter, Open-Label, First-in-Human Study
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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, including adenocarcinoma and neuroendocrine neoplasm in gastrointestinal (GI), esophagus, gastroesophageal junction, pancreas or ampulla, and other solid tumors.

For Part 3 (Histologically or cytologically confirmed diagnosis+ locally advanced unresectable or metastatic disease):CohortA（colorectal adenocarcinoma）: Have clear documentation of rat sarcoma (RAS), vrafmurine sarcoma viral oncogene homolog B (BRAF), and microsatellite instability/mismatch repair status. Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortB（ Human Epidermal Growth Factor Receptor 2 （HER2）-negative gastric, esophageal or gastroesophageal junction adenocarcinoma）: Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortC(pancreatic adenocarcinoma): Participants must have received at least one line of prior cytotoxic chemotherapeutic regimen. CohortD(other advanced solid tumors)

* 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 6 months 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.

Primary outcomes:
measure: Nature and frequency of dose-limiting toxicity(DLT)
timeFrame: Up to approximately 3 years
measure: Nature and frequency of adverse events (AEs) with severity
timeFrame: Up to approximately 3 years
measure: objective response rate (ORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Eastern Cooperative Oncology Group performance status (ECOG PS)
timeFrame: Up to approximately 3 years
measure: To evaluate safety endpoint of peripheral oxygen saturation (SpO2)
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter AUC
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter Cmax
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter Ctrough
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter Tmax
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter CL
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter Vd
timeFrame: Up to approximately 3 years
measure: Characterize Pharmacokinetics(PK) parameter t1/2
timeFrame: Up to approximately 3 years
measure: Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).
timeFrame: Up to approximately 3 years
measure: Disease control rate (DCR)
timeFrame: Up to approximately 3 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 3 years
measure: Time to response (TTR)
timeFrame: Up to approximately 3 years
measure: Depth of response (DpR)
timeFrame: Up to approximately 3 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 3 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
Study officials:
References: