This is a prospective, open-label, phase 2 platform trial. The purpose of this study is to test the safety and effectiveness of the antibody-conjugated drugs (ADCs) in patients with advanced breast cancer who had previously used antibody-conjugated drugs.
This is a prospective, open-label, phase 2 platform trial. The purpose of this study is to test the safety and effectiveness of the antibody-conjugated drugs (ADCs) in patients with advanced breast cancer who had previously received ADCs. The primary endpoint is objective response rate (ORR). This trial aims to learn whether ADC rechallenge works in treating in ADC-treated metastatic breast cancer and identify which ADC works better for subsets on the basis of molecular characteristics and ADC treatment history of their disease with high ORR. Study drugs involved in this study including but not limited to: SHR-A1811 (HER2 ADC), SHR-A1921 (TROP2 ADC), SHR-A2009 (HER3 ADC) and SHR-A2102 (Nectin-4 ADC). This platform trial is adaptive design. Novel ADC regimens with sufficiently high activities that show a high Bayesian predictive probability will graduate from the trial with their corresponding biomarker signature(s). ADCs will be dropped if they show a low probability of improved efficacy with any biomarker signature. New ADCs will enter as those that have undergone testing complete their evaluation. Based on the existing four ADC treatment cohorts on this platform, a maximum of 120 subjects were planned to be enrolled in each ADC treatment cohort. According to the previous ADC treatment history and target, the subjects were randomly assigned to each cohort. On the basis of previous clinical data at our center, we limited the enrollment of a minimum of 10 participants per cohort to avoid underrepresentation of any cohort. During the course of the study, ORR will be evaluated periodically for every additional 10 results according to the Bayesian monitoring method. Graduation (successful validation) or elimination (failed validation) of ADC rechallenge treatment will be considered according to the posterior probability of an ADC cohort and the data of primary efficacy endpoint, secondary efficacy endpoints and safety endpoints. Additional targeted regimens may be added to the platform regimen as feasible as assessed by the investigators, and the protocol will be modified accordingly at that time. The efficacy was evaluated by CT or MRI every 6 weeks (±1 week) according to RECIST 1.1. Subjects with CR or PR were required to have radiologic response confirmation at least 4 weeks. Tumor assessments were performed every 9 weeks (±1 week) after 36 weeks of treatment until disease progression, initiation of new antineoplastic therapy, withdrawal of consent, loss to follow-up, death, or the end of the study, whichever occurred first.
Breast cancer institute of Fudan University Cancer Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGObjective response rate (ORR)
Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol.
Time frame: The observation period related to this endpoint is up to 36 months.
Progression Free Survival (PFS)
PFS based on Kaplan-Meier methodology will be defined as the time from randomization until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation.
Time frame: The observation period related to this endpoint is up to 36 months.
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the proportion of participants with CR, PR and stable disease (SD) for ≥ 4 weeks as the best overall response.
Time frame: The observation period related to this endpoint is up to 36 months.
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) is defined as the proportion of participants with CR, PR and stable disease (SD) for ≥ 24 weeks as the best overall response.
Time frame: The observation period related to this endpoint is up to 36 months.
Duration of Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause). Participants without reported events are censored at the last disease evaluation.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.
A VEGFR inhibitor administered orally per the protocol.
This nutritional formulation is composed primarily of medium-chain triglycerides (MCT), which are metabolized by the liver to induce nutritional ketosis, thereby significantly elevating circulating levels of beta-hydroxybutyrate (BHB).
An anti-HER2 antibody, via intravenous (into the vein) infusion or subcutaneous per protocol.
A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.
A HER2-directed ADC, via intravenous (into the vein) infusion per protocol.
Treatment of physician's choice (TPC), such as nab-paclitaxel, carboplatin, gemcitabine, capecitabine, vinorelbine, eribulin, etc., with specific dosages and administration methods determined at the investigator's discretion.
Time frame: The observation period related to this endpoint is up to 36 months.
Overall Survival (OS)
Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Time frame: The observation period related to this endpoint is up to 5 years.
Treatment-Related Toxicity Rate
The percentage of participants who experienced any grade treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: The observation period related to this endpoint is up to 36 months.