A Study of YL201 in Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05434234
• Recruitment Status: Recruiting
• First Posted: June 27, 2022
• Last Update Posted: May 16, 2023
• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
• Information provided by (Responsible Party): MediLink Therapeutics (Suzhou) Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor	Drug: YL201	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 196 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Multicenter, Nonrandomized, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL201 in Patients With Advanced Solid Tumors
• Actual Study Start Date: May 25, 2022
• Estimated Primary Completion Date: July 2024
• Estimated Study Completion Date: July 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose escalation; All participants enrolled in the dose escalation part	Drug: YL201; Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.
Experimental: Dose expansion; All participants enrolled in the dose expansion part	Drug: YL201; Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.

Outcome Measures

Primary Outcome Measures :

1. Evaluate the occurrence of DLTs during the first cycle in Part 1 [ Time Frame: 21 days of Cycle 1 ]
2. 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 ]
3. Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 2 [ Time Frame: Approximately within 36 months ]
   PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline
4. Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1 [ Time Frame: Approximately within 36 months ]
   ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).

Secondary Outcome Measures :

1. 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 ]
2. Characterize the PK parameter AUC [ Time Frame: Approximately within 36 months ]
3. Characterize the PK parameter Cmax [ Time Frame: Approximately within 36 months ]
4. Characterize the PK parameter Ctrough [ Time Frame: Approximately within 36 months ]
5. Characterize the PK parameter CL [ Time Frame: Approximately within 36 months ]
6. Characterize the PK parameter Vd [ Time Frame: Approximately within 36 months ]
7. Characterize the PK parameter t1/2 [ Time Frame: Approximately within 36 months ]
8. Assess the incidence of anti-YL201 antibodies [ Time Frame: Approximately within 36 months ]
9. Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1 [ Time Frame: Approximately within 36 months ]
   PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline
10. Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer [ Time Frame: Approximately 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.
11. Evaluate the radiological PFS (rPFS) for patients with prostate cancer [ Time Frame: Approximately 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.
12. Evaluate the failure-free survival (FFS) for patients with prostate cancer [ Time Frame: Approximately 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.
13. Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 1, assessed using RECIST version 1.1 [ Time Frame: Approximately within 36 months ]
    ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).
14. 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 ]
    DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD).
15. 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 ]
    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.
16. 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 ]
    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).
17. 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 ]
    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.
18. Evaluate the overall survival (OS) for patients with solid tumors [ Time Frame: Approximately 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Common Inclusion Criteria (Part 1 and Part 2)

• 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 6 months after the last dose of study drug. 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 study drug
• Life expectancy of ≥3 months
• Able and willing to comply with protocol visits and procedures
• Pathologically confirmed diagnosis of an advanced solid tumor for which prior standard treatment had proven to be ineffective or intolerable, or no standard treatment is available

Additional Inclusion Criteria for Part 1

• Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor

Additional Inclusion Criteria for Part 2

• Have at least 1 measurable tumor lesion according to RECIST version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor
• Willing to provide archival or fresh tumor tissue samples. Patients who are not able to provide tumor samples or have inadequate samples may be eligible on a case-by-case basis after discussion with the sponsor

Exclusion Criteria:

Common Exclusion Criteria (Part 1 and Part 2)

• Intolerant to prior treatment with a topoisomerase I inhibitor or an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and Dxd
• 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. The following are exceptions to this criterion:

  1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  2. Systemic steroids at physiological doses as replacement therapy (eg, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency)
  3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
• Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study
• A history of leptomeningeal carcinomatosis
• Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 2 weeks before the first dose of study drug
• Uncontrolled or clinically significant cardiovascular disease
• A history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Clinically significant concomitant pulmonary disease
• Have a diagnosis of Gilbert's syndrome
• Uncontrolled third-space fluid that requires repeated drainage
• Active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation by the investigator's discretion
• Uncontrolled infection that requires systemic therapy within 1 week before the first dose
• 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 not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/exclusion criteria with the exception of alopecia (any grade), pigmentation (any grade), and peripheral neuropathy (Grade ≤2). Patients with irreversible toxicity (eg, hearing loss) that is reasonably not expected to be aggravated by the study drug can 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
• Any illness, medical condition, organ system dysfunction, or social situation, including but not limited to mental illness or substance/alcohol abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results Additional Exclusion Criteria for Part 2
• Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors

Contacts and Locations

Contacts

Contact: Sasha Stann; 617-240-8494; sasha@medilinkthera.com

Contact: Alan Xu, Ph.D.; 617-871-9455; info@medilinkthera.com

Locations

United States, Florida

Hematology Oncology Associates of the Treasure Coast; Recruiting

Port Saint Lucie, Florida, United States, 34952

Contact: Site Coordinator

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Site Coordinator

NEXT San Antonio; Recruiting

San Antonio, Texas, United States, 78229

Contact: Site Coordinator

China, Guangdong

Sun Yat-sen University Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510000

Contact: Site Coordinator

China, Henan

Henan Cancer Hospital; Recruiting

Zhengzhou, Henan, China, 450003

Contact: Site Coordinator

Sponsors and Collaborators

MediLink Therapeutics (Suzhou) Co., Ltd.

More Information

• Responsible Party: MediLink Therapeutics (Suzhou) Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05434234
• Other Study ID Numbers: YL201-INT-101-01
• First Posted: June 27, 2022
• Last Update Posted: May 16, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MediLink Therapeutics (Suzhou) Co., Ltd.:

Antibody-drug conjugate

Additional relevant MeSH terms:

Neoplasms