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A Study of YL201 in Patients With Advanced Solid Tumors

Phase 1
Recruiting
Conditions
Advanced Solid Tumor
Interventions
Drug: YL201 and atezolizumab
Registration Number
NCT05434234
Lead Sponsor
MediLink Therapeutics (Suzhou) Co., Ltd.
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
312
Inclusion Criteria
  • Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF
  • Aged ≥18 years
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
  • Adequate organ and bone marrow function
  • Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of YL201, whichever is later. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of YL201.
  • Life expectancy of ≥3 months
  • Able and willing to comply with protocol visits and procedures
  • Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Pathologically confirmed diagnosis of an advanced solid tumor (SCLC, mCRPC, ESCC and NSCLC are preferred) for which standard treatment had proven to be ineffective or intolerable, or no standard treatment is available. For ES-SCLC patients in Arm C: no prior anti-cancer treatment
Exclusion Criteria
  • Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
  • Prior systemic anticancer treatment including chemotherapy, molecular -targeted therapy, hormonal therapy, immunotherapy, or biological therapy within 3 weeks before the first dose of study drug (use of oral fluorouracil [eg, tegafur and capecitabine] or small molecular-targeted therapy within 2 weeks or 5 half-life periods [whichever is shorter]before the first dose; use of mitomycin or nitrosoureas within 6 weeks before the first dose; use of herbal medicine with antitumor indications or nonspecific immunomodulators [eg, thymosin, interferon, and interleukin] within 2 weeks before the first dose).
  • Prior radiation therapy, including palliative stereotactic radiation with abdominal, within 4 weeks before the first dose of study drug (if palliative stereotactic radiation therapy without abdominal, within 2 weeks)
  • Undergone major surgery (not including diagnostic surgery) within 4 weeks before the first dose of study drug or expect major surgery during the study
  • Undergone allogeneic hematopoietic stem cell transplantation (HSCT) before the first dose of study drug, or autologous HSCT within 3 months before the first dose of study drug
  • Received systemic steroids (>10 mg/day of prednisone or its equivalent) 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
  • Known human immunodeficiency virus (HIV) infection
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA level above ULN at the study site; active HCV is defined as positive hepatitis C antibody and HCV RNA level above ULN at the study site
  • Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and pigmentation) not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/exclusion criteria. Patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be enrolled after discussion with the sponsor
  • A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other mAbs
  • Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 7 days before the first dose

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose escalationYL201All participants enrolled in the dose escalation part
Dose expansionYL201All participants enrolled in the dose expansion part
Dose SelectionYL201 and atezolizumab-
Primary Outcome Measures
NameTimeMethod
Laboratory abnormalities as characterized by type, frequency, severity, and timing in Part 2Biy 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 3Biy the end of trial date, approximately within 36 months
Evaluate the occurrence of DLTs during the first cycle in Part 121 days of Cycle 1
Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatmentBy 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 2Approximately within 36 months

PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline

Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1Approximately within 36 months

ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).

Nature and frequency of dose-limiting toxicities (DLTs), incidence, nature, and severity of laboratory abnormalities in Part 3At the end of cycle 1 (each cycle is 21 days)
Secondary Outcome Measures
NameTimeMethod
Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatmentBy the global end of trial date, approximately within 36 months
Characterize the PK parameter AUCApproximately within 36 months
Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1Approximately within 36 months

PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline

Evaluate the failure-free survival (FFS) for patients with prostate cancerApproximately within 36 months

FFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of radiographic tumor progression, unequivocal clinical progression, PSA progression or death due to disease progression, whichever occurs first.

Evaluate the time to response (TTR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1Approximately within 36 months

TTR: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of objective response (CR or PR).

Characterize the PK parameter CmaxApproximately within 36 months
Characterize the PK parameter CtroughApproximately within 36 months
Characterize the PK parameter VdApproximately within 36 months
Characterize the PK parameter t1/2Approximately within 36 months
Evaluate the radiological PFS (rPFS) for patients with prostate cancerApproximately within 36 months

rPFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of radiographic tumor progression or death due to any cause, whichever occurs first, based on RECIST 1.1 and PCWG3 criteria.

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 1.1Approximately within 36 months

ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).

Evaluate the duration of response (DoR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1Approximately within 36 months

DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of PD. DoR will be assessed for patients with a response (CR or PR) only.

Characterize the PK parameter CLApproximately within 36 months
Assess the incidence of anti-YL201 antibodiesApproximately within 36 months
Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancerApproximately within 36 months

PSA-PFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of PSA progression, based on PCWG3 criteria.

Evaluate the disease control rate (DCR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1Approximately within 36 months

DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD).

Evaluate the overall survival (OS) for patients with solid tumorsApproximately within 36 months

OS: defined as the time interval from the date of the first dose of study drug to the date of death due to any cause.

Evaluate the progression-free survival (PFS) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1Approximately within 36 months

PFS: defined as the time interval from the date of the first dose of study drug to the date of first documentation of PD or death due to any cause, whichever occurs first.

Trial Locations

Locations (45)

002

🇺🇸

Fair Oaks, California, United States

001

🇺🇸

La Jolla, California, United States

003

🇺🇸

Lone Tree, Colorado, United States

004

🇺🇸

Washington D.C., District of Columbia, United States

005

🇺🇸

Boston, Massachusetts, United States

006

🇺🇸

Ann Arbor, Michigan, United States

007

🇺🇸

Detroit, Michigan, United States

008

🇺🇸

St Louis, Missouri, United States

009

🇺🇸

Santa Fe, New Mexico, United States

010

🇺🇸

New York, New York, United States

Scroll for more (35 remaining)
002
🇺🇸Fair Oaks, California, United States
Study Coordinator
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