Study of Disitamab Vedotin With Toripalimab Verus Disitamab Vedotin in Hormone Receptor Positive, HER2-low Locally Advanced or Metastatic Breast Cancer

Recruitment & Eligibility

Status: Withdrawn

Sex: All

Target Recruitment: 0

Inclusion Criteria

Inclusion Criteria: 1. Age 18 years and older years at the time of consent 2. Pathologically confirmed breast cancer 3. Stage III unresectable locally advanced or stage IV metastatic breast cancer. 4. Subjects must be willing and able to provide recent non-previously radiotherapy metastases lesions (if feasible and available) to the sponsor-designated central laboratory prior to treatment initiation or, if not feasible or available, tumor tissue blocks (or fresh tissue sections, see laboratory manuals) obtained from locally recurrent lesions for biomarker analysis, including HER2 expression and HR status. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor lesion is required within 28 days prior to Cycle 1 Day 1. Biopsy must provide adequate tissue for analysis. 5. Subjects must have HER2 low expression (defined as IHC 1+ or IHC 2+/ISH-) and HR+ status (defined as recent tumor showing ER and/or PR expression =1% [according to ASCO/CAP 2020 guidelines]) determined by the central laboratory. 6. The subject must meet all of the following criteria: 1. must not have received prior chemotherapy (including ADC) in the unresectable locally advanced or metastatic disease setting 2. have undergone endocrine therapy, or patients with weak ER-positivity (1 to 10% nuclear positivity) were eligible if they were not candidates for endocrine therapy after an adequate assessment by the investigator - disease recurrence or progression during adjuvant endocrine therapy period or within 12 months after completion of adjuvant endocrine therapy, either alone or in combination with CDK4/6 inhibitors, OR - received prior endocrine therapy with documented disease progression during treatment period or thereafter in the unresectable locally advanced or metastatic disease setting, either alone or in combination with CDK4/6 inhibitors 7. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 assessed within 7 days prior to randomization. 8. Measurable disease as defined in RECIST v1.1 9. The following baseline laboratory data indicating adequate organ function: 1. ANC =1,500/µL 2. platelet count =100,000/µL 3. hemoglobin =9.0 g/dL or =5.6 mmol/L 4. total bilirubin =1.5 × upper limit normal (ULN) OR direct bilirubin =ULN for subjects with total bilirubin >1.5 × ULN. Serum bilirubin =3× ULN for subjects with Gilbert's disease 5. CrCl =40 mL/min (measured by the Cockcroft-Gault formula as applicable, or 24-hour urine). 6. ALT and AST =2.5× ULN without liver metastases or =5× ULN with liver metastases 7. International normalized ratio (INR) or prothrombin time (PT) =1.5× ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants 10. Subjects of childbearing potential under the following conditions: 1. Must have a negative serum pregnancy test (minimum sensitivity 25 mIU/mL or equivalent units of beta human chorionic gonadotropin [ß-hCG]) result within 7 days prior to the first dose of RC48-ADC. Subjects with false positive results and documented verification that the subject is not pregnant are eligible for participation. 2. Must agree not to try to become pregnant during the study and for at least 4 months for subjects after the final dose of study drug. 3. Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 4 months for subjects after the final dose of study drug. 4. If sexually active in a way that could lead to pregnancy, must consistently use at least 2 acceptable methods of birth control (contraception), at least one of which must be highly effective through at least 4 months for subjects after the final dose of study drug. 11. Subjects who can get someone pregnant (as defined in Section 10.4) under the following conditions: 1. Must agree not to donate sperm starting at time of informed consent and continuing through at least 4 months after the final dose of RC48-ADC. 2. If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use at least 2 acceptable methods of birth control (contraception), at least one of which must be highly effective starting at time of informed consent and continuing through at least 4 months after the final dose of RC48-ADC. 3. If sexually active with a person who is pregnant or breastfeeding, must consistently use a condom starting at time of informed consent and continuing through at least 4 months after the final dose of RC48-ADC. 12. The subject must provide documented informed consent. Exclusion Criteria: 1. Known hypersensitivity to any excipient contained in the drug formulation of RC48-ADC, or pembrolizumab. 2. Prior anti-HER2 therapy, including an ADC. 3. Prior MMAE-containing agent 4. Prior immunotherapy including anti-PD-(L)1 or anti-PD-(L)2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CD137, CTLA-4, OX-40) in the LA/m setting ([neo]adjuvant anti-PD-(L)1 is allowed if last dose is =12 months prior to recurrence or progression). 5. History of another malignancy within 3 years prior to screening, with the exception of those with a negligible risk of metastasis or death (eg, approximate 5-year OS of =90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. 6. Subjects with known active CNS or leptomeningeal metastasis are excluded. Subjects with definitively treated brain metastasis (surgery and/or radiotherapy) are eligible if the following criteria are met: 1. All known CNS lesions have been treated. 2. No evidence of clinical and radiographic disease progression in the CNS for =4 weeks after definitive treatment. 3. Neurological symptoms attributed to brain metastases have returned to baseline. 4. No utilization of steroids to manage symptoms related to CNS disease or its treatment within 14 days of randomization. Anti-convulsant therapy is allowed if the dose has been stable for 14 days. 7. Subjects with prior allogenic tissue/solid organ or bone marrow transplantation. 8. Subjects with acute, chronic, or symptomatic infections, including: 1. Active infection requiring systemic treatment =7 days before dose of study drug. Routine antimicrobial prophylaxis is permitted. 2. Known positivity for hepatitis B (HBsAg positive with HBV DNA titers above the upper limit of normal), active hepatitis C infection (positive by polymerase chain reaction [PCR] or on antiviral t

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS), evaluated by investigator

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS);Objective Response Rate (ORR);Disease Control Rate (DCR);Duration of response (DoR);Type, incidence, relatedness, severity, and seriousness of AEs;Incidence of laboratory tests abnormalities;Incidence of ECG abnormalities;Incidence of echocardiograms abnormalities;Health-related quality of life - EORTC-QLQ-C30

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Study of Disitamab Vedotin With Toripalimab Verus Disitamab Vedotin in Hormone Receptor Positive, HER2-low Locally Advanced or Metastatic Breast Cancer

Recruitment & Eligibility

Study & Design

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