A Phase 1A/1B, Multicenter, Nonrandomized, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL201 as a Single Agent and in Combination With Other Anti-Cancer Therapies in Patients With Advanced Solid Tumors
Summary
This is a phase 1, multicenter, nonrandomized, open-label, first-in-human study of YL201 conducted in China and the United States. The study will include 2 parts: a dose escalation part (Part 1) followed by a dose expansion part (Part 2). Part 1 will estimate the MTD/RED(s) in dose escalation cohorts of patients with advanced solid tumors unresponsive to currently available therapies or for whom no standard therapy is available. Part 2 will include patients with selected advanced solid tumor types enrolled at the MTD/RED(s), to better define the safety profile and evaluate the efficacy of YL201.
Arms & interventions
- DrugYL201
Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.
- DrugYL201
Patients will be treated with YL201 intravenous (IV) (A mg/kg or B g/kg infusion once every 3 weeks (Q3W) as a cycle.
- DrugYL201 and atezolizumab
Patients will be treated with YL201 intravenous (IV) infusion (A mg/kg or B mg/kg, up to 200mg) followed by atezolizumab on day 1 of each 21 day cycle
Outcome measures
Primary
Evaluate the occurrence of DLTs during the first cycle in Part 1
Time frame: 21 days of Cycle 1
Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
Time frame: By the global end of trial date, approximately within 36 months
Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 2
PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline
Time frame: Approximately within 36 months
Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1
ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).
Time frame: Approximately within 36 months
Laboratory abnormalities as characterized by type, frequency, severity, and timing in Part 2
Time frame: Biy the end of trial date, approximately within 36 months
Incidence, nature, and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in Part 3
Time frame: Biy the end of trial date, approximately within 36 months
Nature and frequency of dose-limiting toxicities (DLTs), incidence, nature, and severity of laboratory abnormalities in Part 3
Time frame: At the end of cycle 1 (each cycle is 21 days)
Secondary
Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
Time frame: By the global end of trial date, approximately within 36 months
Characterize the PK parameter AUC
Time frame: Approximately within 36 months
Characterize the PK parameter Cmax
Time frame: Approximately within 36 months
Characterize the PK parameter Ctrough
Time frame: Approximately within 36 months
Characterize the PK parameter CL
Time frame: Approximately within 36 months
Characterize the PK parameter Vd
Time frame: Approximately within 36 months
Characterize the PK parameter t1/2
Time frame: Approximately within 36 months
Assess the incidence of anti-YL201 antibodies
Time frame: Approximately within 36 months
Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1
Time frame: Approximately within 36 months
Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer
Time frame: Approximately within 36 months
Evaluate the radiological PFS (rPFS) for patients with prostate cancer
Time frame: Approximately within 36 months
Evaluate the failure-free survival (FFS) for patients with prostate cancer
Time frame: Approximately within 36 months
Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 1, Part 2, and Part 3, assessed using RECIST version 1.1
Time frame: Approximately within 36 months
Evaluate the disease control rate (DCR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
Time frame: Approximately within 36 months
Evaluate the duration of response (DoR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
Time frame: Approximately within 36 months
Evaluate the time to response (TTR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
Time frame: Approximately within 36 months
Evaluate the progression-free survival (PFS) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
Time frame: Approximately within 36 months
Evaluate the overall survival (OS) for patients with solid tumors
Time frame: Approximately within 36 months
Eligibility criteria
Study locations (19)
002
Fair Oaks, California, 95628
001
La Jolla, California, 92093-0698
003
Lone Tree, Colorado, 80124
004
Washington D.C., District of Columbia, 20007
005
Boston, Massachusetts, 02114
006
Ann Arbor, Michigan, 48109
007
Detroit, Michigan, 48292
008
St Louis, Missouri, 63110
009
Santa Fe, New Mexico, 87505-699
010
New York, New York, 10029
011
Chapel Hill, North Carolina, 27514
012
Nashville, Tennessee, 37203
014
Houston, Texas, 77030
015
Irving, Texas, 75039
013
San Antonio, Texas, 78229
016
Tyler, Texas, 75701
017
Fairfax, Virginia, 22031
018
Spokane, Washington, 99208
019
Tacoma, Washington, 98405
References
- Ma Y, Yang Y, Huang Y, Fang W, Xue J, Meng X, Fan Y, Fu S, Wu L, Zheng Y, Liu J, Liu Z, Zhuang W, Rosen S, Qu S, Li B, Li M, Zhao Y, Yang S, Ji Y, Sommerhalder D, Luo S, Yang K, Li J, Lv D, Zhang P, Zhao Y, Hong S, Zhang Y, Zhao S, Chin S, Zhang X, Lian W, Cai J, Xue T, Zhang L, Zhao H. A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial. Nat Med. 2025 Jun;31(6):1949-1957. doi: 10.1038/s41591-025-03600-2. Epub 2025 Mar 13.(PubMed)