Clinical trial NCT06439771: A Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of YL202 in Patients With BC
Official title: A Multicenter, Open-Label, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of YL202 in Patients With Locally Advanced or Metastatic Breast Cancer With TNBC, HR-Positive, HER2-Zero-expression or HER2-Low-expression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced or Metastatic Breast Cancer
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-03
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, open-label, phase 2 clinical study to evaluate the efficacy, safety and pharmacokinetics of YL202 in patients with locally advanced or metastatic breast cancer with TNBC, HR-positive, HER2-zero-expression or HER2-low-expression


Eligibility criteria: Inclusion Criteria:

1. Have been informed of the study before the start of the study and voluntarily sign name and date on the informed consent form.
2. Patients with locally advanced or metastatic disease (according to the UICC and AJCC staging system \[Version 8\]) who are not candidates for curative surgery or radiotherapy.
3. Patients who are pathologically confirmed advanced/unresectable or metastatic breast cancer with HR-negative and HER2-negative,.
4. Patients who are confirmed HR positive and HER2-Zero-expression and HER2-Low-expression.
5. Breast cancer patients who have previously failed treatments of HER2-ADC or TROP2-ADC.
6. Have at least 1 extracranial measurable lesion as a target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
7. Have Adequate organ and bone marrow function within 7 days prior to the first dose.
8. Female patients of childbearing potential must agree to use highly effective contraception from screening throughout the duration of the study and for at least 6 months after the last dose of study drug.
9. Have a expected survival ≥ 3 months.
10. Have ability and willingness to comply with protocol-specified visits and procedures.

Exclusion Criteria:

1. Have prior treatment with an agent targeting HER3.
2. Have prior intolerance to treatment with topoisomerase I inhibitor or an ADC that consists of topoisomerase I inhibitor.
3. Have been enrolled in another clinical study concurrently unless it is an observational clinical study or in the follow-up phase of an interventional study.
4. Have insufficient washout period for prior anticancer therapy prior to first dose of the study drug.
5. Have major surgery (excluding diagnostic surgery) within 4 weeks prior to the first dose of study drug or anticipation of major surgery during the study.
6. Have prior allogeneic bone marrow transplant or prior solid organ transplant.
7. Have received treatment with systemic steroids.
8. Have received any live vaccine within 4 weeks prior to the first dose of study drug or intend to receive a live vaccine during the study.
9. Leptomeningeal metastases or carcinomatous meningitis, spinal cord compression.
10. Brain metastases with the exceptions.
11. Have uncontrolled or clinically significant cardiovascular and cerebrovascular disease.
12. Have clinically significant concomitant pulmonary diseases.
13. Have a diagnosis of Gilbert's syndrome.
14. Have pleural effusion, abdominal effusion.
15. Have a history of gastrointestinal perforation and or fistula within 6 months prior to the first dose.
16. Have serious infection.
17. Patients with human immunodeficiency virus (HIV) infection.
18. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
19. Have any other primary malignancy within 5 years prior to the first dose of study drug.
20. Have unresolved toxicities from prior anticancer therapy.
21. Have a history of severe hypersensitivity reactions to the drug substance, inactive ingredients in the drug product, or other monoclonal antibodies.
22. Lactating women, or women who are confirmed to be pregnant by pregnancy test within 3 days prior to the first dose.

Primary outcomes:
measure: ORR assessed according to RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Determination of the recommended dose of YL202 in the pivotal clinical study
timeFrame: By the end of trial date, approximately within 36 months
Secondary outcomes:
measure: Progression-free survival (PFS) assessed according to RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Clinical benefit rate (CBR) assessed based on RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Depth of response (DpR) assessed based on RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Disease control rate (DCR) assessed based on RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Duration of response (DOR) assessed based on RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Time to response (TTR) assessed based on RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Evaluate the overall survival (OS)
timeFrame: By the end of trial date, approximately within 36 months
measure: Adverse event (AE), described in terms of type, frequency, severity, time, and relationship with study treatment
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter AUC
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Cmax
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Ctrough
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter CL
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Vd
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter t1/2
timeFrame: Approximately within 36 months
measure: Incidence of anti-YL202 antibody
timeFrame: Approximately within 36 months
measure: Evaluate the corelaton between different levels of HER3 expression and the sum of CR rate, PR rate and SD rate
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: