NCT06649331

Platform Study of ADC Rechallenge in ADC-treated Metastatic Breast Cancer

Platform Study of ADC Rechallenge in ADC-treated Metastatic Breast Cancer：A Prospective, Open-label, Phase 2 Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Advanced Breast Cancer
• Metastatic Breast Cancer
• Triple Negative Breast Cancer (TNBC)
• HER2-negative Breast Cancer
• Breast Cancer

Interventions

Type	Name	Description
DRUG	SHR-A1811	A HER2-directed ADC, via intravenous (into the vein) infusion per protocol.
DRUG	SHR-A1921	A TROP2-directed ADC, via intravenous (into the vein) infusion per protocol.
DRUG	SHR-A2009	A HER3-directed ADC, via intravenous (into the vein) infusion per protocol.
DRUG	SHR-A2102	A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.
DRUG	Famitinib	A VEGFR inhibitor administered orally per the protocol.
DIETARY_SUPPLEMENT	Fat Module Formula for Special Medical Purposes	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).
DRUG	Trastuzumab (or biosimilar)	An anti-HER2 antibody, via intravenous (into the vein) infusion or subcutaneous per protocol.
DRUG	9MW2821	A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.

Timeline

• Start date: 2024-10-21
• Primary completion: 2026-09-01
• Completion: 2027-09-01
• First posted: 2024-10-18
• Last updated: 2026-04-08

Locations

1 site across 1 country: China