A Study of YL202 in Selected Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is a multicenter, open-label, phase II study of YL202 in China to evaluate the efficacy, safety, and PK characteristics of YL202 in the following selected patients with advanced solid tumors.

Detailed Description
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This study is a multicenter, open-label, phase II study of YL202 in China to evaluate the efficacy, safety, and PK characteristics of YL202 in the advanced NSCLC/BC/HNSCC/colorectal cancer/HER2-positive gastric cancer/cervical cancer/ovarian cancer and etc.

Official Title
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A Multicenter, Open-Label, Phase II Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of YL202 in Selected Patients With Advanced Solid Tumors

Conditions
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NSCLC, Breast Cancer, HNSCC, Locally Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: YL202 should be intravenously infused


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are aware of relevant trial information before the start of the trial, and voluntarily sign and date on the informed consent form (ICF). Subjects aged from 18-75 (inclusive) years. Histologically or cytologically confirmed at diagnosis of NSCLC/BC/HNSCC/other locally advanced or metastatic solid tumors including but not limited to colorectal cancer, HER2-positive gastric cancer, cervical cancer, ovarian cancer, etc.. At least one extracranial measurable lesion according to RECIST 1.1. Archived or fresh tumor tissue samples can be provided. With Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. The function of organs and bone marrow meets the requirements within 7 days before the first dose. Female subjects of childbearing potential must agree to adopt highly effective contraceptive measures from screening throughout the study period and within at least 6 months after the last dose of the investigational product. Male subjects must agree to adopt highly effective contraceptive measures from screening throughout the study period and within at least 6 months after the last dose of the investigational product. With expected survival ≥ 3 months. Be capable of and willing to comply with the visits and procedures stipulated in the study protocol. Exclusion Criteria: With prior drug therapy targeting HER3 (including antibodies, antibody-drug conjugates [ADCs]), chimeric antigen receptor T-cell immunotherapy (CAR-T), and other drugs). Previously intolerant to topoisomerase I inhibitors or ADC therapy composed of topoisomerase I inhibitors. Are participating in another clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study. The washout period from the previous anti-tumor therapy is insufficient before the first dose of the investigational product. Patients who have received major surgery (excluding diagnostic surgery) within 4 weeks before the first dose of the investigational product or those who are expected to receive major surgery during the study. Prior treatment with allogeneic bone marrow transplantation or solid organ transplantation. Prior treatment with systemic steroids (prednisone > 10 mg/day or equivalent) or other immunosuppressive treatment within 2 weeks before the first dose of the investigational product. Patients who have received any live vaccine within 4 weeks before the first dose of the investigational product or those who plan to receive live vaccine during the study period. With meningeal metastasis or cancerous meningitis. With brain metastasis or spinal cord compression. Patients with uncontrolled or clinically significant cardiovascular diseases. Clinically significant complicated pulmonary disorders. Patients diagnosed with Gilbert syndrome. Those with uncontrolled effusion in the third space requiring repeated drainage. With a medical history of gastrointestinal perforation and/or fistula within 6 months before the first dose, or with active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal diseases that may lead to hemorrhage or perforation according to the investigator. With serious infection before the first dose. With known human immunodeficiency virus (HIV) infection. With active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. With a medical history of any other primary malignancies within 5 years before the first dose of the investigational product. Unrelieved toxicity of previous anti-tumor therapy. With a history of severe hypersensitivity to inactive ingredients in the raw materials and drug product or other monoclonal antibodies. Lactating women, or women who are confirmed pregnant via a pregnancy test within 3 days before the first dose. With any diseases, medical conditions, organ system dysfunction, or social conditions that may interfere with the ability of subjects to sign the ICF, adversely affect the ability of subjects to cooperate and participate in the study, or affect the interpretation of study results, including but not limited to mental illness or substance/alcohol abuse, in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Corhort A<br>YL202 is provided as the lyophilized powder, 200 mg/vial. Locally advanced or metastatic NSCLC patients will be given YL202 by intravenously once every 3 weeks (Q3W) as a cycle. | Drug: YL202 should be intravenously infused<br>* For each patient, YL202 should be intravenously infused over 60±10 min.<br>|
| Experimental: Corhort B<br>YL202 is provided as the lyophilized powder, 200 mg/vial. Locally advanced or metastatic BC patients will be given YL202 by intravenously once every 3 weeks (Q3W) as a cycle. | Drug: YL202 should be intravenously infused<br>* For each patient, YL202 should be intravenously infused over 60±10 min.<br>|
| Experimental: Corhort C<br>YL202 is provided as the lyophilized powder, 200 mg/vial. Locally advanced or metastatic HNSCC patients will be given YL202 by intravenously once every 3 weeks (Q3W) as a cycle. | Drug: YL202 should be intravenously infused<br>* For each patient, YL202 should be intravenously infused over 60±10 min.<br>|
| Experimental: Corhort D<br>YL202 is provided as the lyophilized powder, 200 mg/vial. Other locally advanced cancer patients will be given YL202 by intravenously once every 3 weeks (Q3W) as a cycle. | Drug: YL202 should be intravenously infused<br>* For each patient, YL202 should be intravenously infused over 60±10 min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR assessed according to RECIST v1.1 | ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR). | By the end of trial date, approximately within 36 months | 
| Determination of the recommended dose of YL202 in the pivotal clinical study |  | By the end of trial date, approximately within 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) assessed according to RECIST v1.1 |  | approximately within 36 months | 
| Clinical benefit rate (CBR) assessed according to RECIST v1.1 |  | approximately within 36 months | 
| depth of response (DpR) assessed according to RECIST v1.1 |  | Approximately within 36 months | 
| disease control rate (DCR) assessed according to RECIST v1.1 |  | Approximately within 36 months | 
| duration of response (DOR) assessed according to RECIST v1.1 |  | Approximately within 36 months | 
| time to response (TTR) assessed according to RECIST v1.1 |  | Approximately within 36 months | 
| Evaluate the overall survival (OS) |  | Approximately within 36 months | 
| Adverse event (AE), described in terms of type, frequency, severity, time, and relationship with study treatment |  | Approximately within 36 months | 
| Characterize the PK parameter AUC | steady-state area under curve (AUC) | Approximately within 36 months | 
| Characterize the PK parameter Cmax | peak concentration (Cmax) | Approximately within 36 months | 
| Characterize the PK parameter Ctrough | trough concentration (Ctrough) | Approximately within 36 months | 
| Characterize the PK parameter CL | clearance (CL) | Approximately within 36 months | 
| Characterize the PK parameter Vd | volume of distribution (Vd) | Approximately within 36 months | 
| Characterize the PK parameter t1/2 | half-life (t1/2) | Approximately within 36 months | 
| Incidence of anti-YL202 antibody |  | approximately within 36 months | 
| Establish a POP PK model for exposure-response relationship analysis |  | approximately within 36 months | 
| Evaluate the relatonship between different levels of HER3 expression and the sum of CR rate, PR rate and SD rate |  | 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