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

Description
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

Objective
Dose-Escalation Part (Part 1)

Primary Objectives:
-To assess the safety and tolerability of YL217 in participants with advanced solid tumors
-To determine the maximum tolerated dose (MTD) of YL217 in participants with advanced solid tumors

Secondary Objectives:
-To characterize the pharmacokinetics (PK) of YL217 antibody-drug conjugate (YL217-ADC), YL217 total antibody (YL217-TAb), and unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
-To evaluate immunogenicity as measured by the presence of anti-drug antibodies (ADAs) in participants treated with YL217
-To document any preliminary efficacy of YL217 in participants with advanced solid tumors

Backfill Part (Part 2)

Primary Objectives:
-To further evaluate the safety and tolerability of YL217 in participants with advanced solid tumors
-To determine the recommended dose(s) for expansion (RDE(s)) of YL217 in participants with advanced solid tumors

Secondary Objectives:
-To further evaluate the efficacy of YL217 in participants with advanced solid tumors
-To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
-To evaluate immunogenicity as measured by the presence of ADAs in participants treated with YL217

Dose-Expansion Part (Part 3)

Primary Objectives:
-To further evaluate the efficacy of YL217 at the RDE(s) in participants with the selected advanced solid tumors such as colorectal adenocarcinoma, gastric, esophageal or gastroesophageal junction adenocarcinoma, and pancreatic adenocarcinoma
-To determine the recommended phase 2 dose (RP2D) of YL217

Secondary Objectives:
-To further evaluate the safety and tolerability of YL217 at the RDE(s) in participants with the selected advanced solid tumors
-To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
-To evaluate immunogenicity as measured by the presence of ADAs in participants treated with YL217

Treatment 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.

Key Eligibility 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.

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital