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

NCT06649331 | Recruiting Phase 2

• 1 other identifier: SCHBCC-N076
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

platform trial; adaptive design; antibody-conjugated drugs (ADCs); Bayesian predictive probability

Outcome Measures

Primary Outcomes (1)

• Objective 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.

  The observation period related to this endpoint is up to 36 months.

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  The observation period related to this endpoint is up to 36 months.

• Disease Control Rate (DCR)

  The observation period related to this endpoint is up to 36 months.

• Clinical Benefit Rate (CBR)

  The observation period related to this endpoint is up to 36 months.

• Duration of Response (DOR)

  The observation period related to this endpoint is up to 36 months.

• Overall Survival (OS)

  The observation period related to this endpoint is up to 5 years.

Other Outcomes (1)

• Exploration of translational research markers

  The observation period related to this endpoint is up to 36 months.

Study Arms (8)

A

EXPERIMENTAL

SHR-A1811 (HER2 ADC)

Drug: SHR-A1811

B

EXPERIMENTAL

SHR-A1921 (TROP2 ADC)

Drug: SHR-A1921

C

EXPERIMENTAL

SHR-A2009 (HER3 ADC)

Drug: SHR-A2009

D

EXPERIMENTAL

SHR-A2102 (Nectin4 ADC)

Drug: SHR-A2102

E

EXPERIMENTAL

SHR-A1811 (HER2 ADC) and Famitinib (VEGFR inhibitor)

Drug: SHR-A1811; Drug: Famitinib

F

EXPERIMENTAL

SHR-A1811 (HER2 ADC) and Fat Module Formula for Special Medical Purposes (for Medium-Chain Triglyceride Supplementation)

Drug: SHR-A1811; Dietary Supplement: Fat Module Formula for Special Medical Purposes

G

EXPERIMENTAL

9MW2821 (Nectin4 ADC)

Drug: 9MW2821

H

EXPERIMENTAL

9MW2821 (Nectin4 ADC) + trastuzumab

Drug: Trastuzumab (or biosimilar); Drug: 9MW2821

Interventions

SHR-A1921 DRUG

A TROP2-directed ADC, via intravenous (into the vein) infusion per protocol.

B

SHR-A2009 DRUG

A HER3-directed ADC, via intravenous (into the vein) infusion per protocol.

C

SHR-A2102 DRUG

A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.

D

SHR-A1811 DRUG

A HER2-directed ADC, via intravenous (into the vein) infusion per protocol.

A; E; F

Famitinib DRUG

A VEGFR inhibitor administered orally per the protocol.

E

Fat Module Formula for Special Medical Purposes DIETARY_SUPPLEMENT

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).

F

Trastuzumab (or biosimilar) DRUG

An anti-HER2 antibody, via intravenous (into the vein) infusion or subcutaneous per protocol.

H

9MW2821 DRUG

A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.

G; H

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;
• Previously received ADCs;
• The most recent pathology results will be considered for enrollment according to local testing of ER, PR and HER2. Participants with any hormone receptor (HR) status will be allowed on study.
• Prior endocrine therapy: Participants with HR-positive breast cancer must have received prior CDK4/6 inhibitor;
• Participants must have measurable disease per RECIST 1.1.
• The functions of the main organs are basically normal and meet the following conditions:
• I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 10\^9 / L; PLT acuity 75 x 10\^9 / L; II. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula); III. LVEF≥50%
• They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity; Participants may have discontinued all CDK4/6 inhibitor at least 14 days prior to study treatment initiation. Prior endocrine therapy does not require washout.
• ECOG score ≤2, and life expectancy ≥3 months;
• Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug;
• Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.

You may not qualify if:

• Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis);
• Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol);
• A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months;
• Presence of the third space effusion (such as massive ascites, pleural effusion, pericardial effusion) that cannot be controlled by drainage or other methods;
• Participants with who had used immunosuppressive agents or systemic corticosteroids within 2 weeks before the first dose (dose\> 10mg/day prednisone or other corticosteroids at the physiological dose of the drug), excluding nasal spray or inhaled corticosteroids;
• Presence of any active autoimmune disease or a history of autoimmune disease with potential relapse;
• Known human immunodeficiency virus (HIV) infection that is not well controlled;
• Known active hepatitis B (HBV DNA≥2000 IU/mL or 104 copies/mL) and hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower detection limit of the assay);
• Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes;
• Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment;
• Pregnant or lactating patients;
• Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years;
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications;
• Serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results
• Deemed by the investigator to be ineligible for participation in the study.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Breast cancer institute of Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

famitinib; Trastuzumab; Biosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Zhimin Shao, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimin Shao, M.D.

CONTACT

86-21-64175590; Zhimingshao@yahoo.com

Xiyu Liu, M.D.

CONTACT

86-21-64175590; 10301010079@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 18, 2024
• Study Start: October 21, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)