A Study of YL201 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: YL201


Participation Criteria
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Eligibility Criteria
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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: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection) Systemic steroids at physiological doses as replacement therapy (eg, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>All participants enrolled in the dose escalation part | Drug: YL201<br>* Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.<br>|
| Experimental: Dose expansion<br>All participants enrolled in the dose expansion part | Drug: YL201<br>* Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the occurrence of DLTs during the first cycle in Part 1 |  | 21 days of Cycle 1 | 
| Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment |  | 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 | 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). | Approximately within 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment |  | By the global end of trial date, approximately within 36 months | 
| Characterize the PK parameter AUC |  | Approximately within 36 months | 
| Characterize the PK parameter Cmax |  | Approximately within 36 months | 
| Characterize the PK parameter Ctrough |  | Approximately within 36 months | 
| Characterize the PK parameter CL |  | Approximately within 36 months | 
| Characterize the PK parameter Vd |  | Approximately within 36 months | 
| Characterize the PK parameter t1/2 |  | Approximately within 36 months | 
| Assess the incidence of anti-YL201 antibodies |  | Approximately within 36 months | 
| Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1 | PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline | Approximately within 36 months | 
| Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer | 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. | Approximately within 36 months | 
| Evaluate the radiological PFS (rPFS) for patients with prostate cancer | 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. | Approximately within 36 months | 
| Evaluate the failure-free survival (FFS) for patients with prostate cancer | 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. | Approximately within 36 months | 
| Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 1, 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). | 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 | DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD). | 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 | 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. | 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 | 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). | 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 | 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. | Approximately within 36 months | 
| Evaluate the overall survival (OS) for patients with solid tumors | 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. | Approximately within 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody-drug conjugate