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

Plain English Summary

Platform Study of ADC Rechallenge in ADC-treated Metastatic Breast Cancer is a Phase 2 clinical trial sponsored by Fudan University studying Advanced Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative Breast Cancer, Breast Cancer. This study tests if new antibody-drug combinations are safe and effective in patients with advanced breast cancer who have already received antibody treatments. It is for adults (18+) with locally advanced or metastatic breast cancer that has spread and who have previously been treated with antibody-drug conjugates. Participation involves receiving study drugs intravenously and regular check-ups. Alternatives may include standard treatments or palliative care. This trial aims to find new options for patients whose breast cancer has progressed after initial antibody therapy. The trial aims to enroll 160 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have advanced or metastatic breast cancer, and have previously received antibody-drug treatments. You cannot join if you have uncontrolled brain metastases, certain heart conditions, or active autoimmune diseases. Your organ function (blood, liver, kidney) must be generally normal, and you should not have had recent radiation, chemotherapy, or surgery. Participants must have measurable disease and an ECOG score of 2 or less, indicating a reasonable ability to perform daily activities. This trial is studying Advanced Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative Breast Cancer, Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how often the study drugs shrink tumors, indicating their effectiveness in controlling the cancer. The specific primary outcome measures are: Objective response rate (ORR) (The observation period related to this endpoint is up to 36 months.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for new treatment strategies in patients with advanced breast cancer who have exhausted standard antibody-drug conjugate therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative Breast Cancer, Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial explores novel antibody-drug conjugates in a growing market for advanced breast cancer therapies, with potential for significant patient benefit if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific antibody drugs being tested, potential side effects, and how often you'll need to visit the clinic. Participation involves receiving study drugs through an IV infusion and attending regular appointments for monitoring and assessments. Be prepared for regular blood tests and scans to check how your body is responding to the treatment and to monitor for any side effects. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 160 participants

Interventions

• 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.

Primary Outcomes

• Objective response rate (ORR) (The observation period related to this endpoint is up to 36 months.)

Secondary Outcomes

• 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.)

Full Eligibility Criteria

Inclusion Criteria:

1. Age ≥18 years;
2. Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;
3. Previously received ADCs;
4. 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.
5. Prior endocrine therapy: Participants with HR-positive breast cancer must have received prior CDK4/6 inhibitor;
6. Participants must have measurable disease per RECIST 1.1.
7. 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%
8. 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.
9. ECOG score ≤2, and life expectancy ≥3 months;
10. 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;
11. Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

1. 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);
2. Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol);
3. 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;
4. Presence of the third space effusion (such as massive ascites, pleural effusion, pericardial effusion) that cannot be controlled by drainage or other methods;
5. 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;
6. Presence of any active autoimmune disease or a history of autoimmune disease with potential relapse;
7. Known human immunodeficiency virus (HIV) infection that is not well controlled;
8. 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);
9. 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;
10. Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment;
11. Pregnant or lactating patients;
12. Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years;
13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications;
14. Serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results
15. Deemed by the investigator to be ineligible for participation in the study.

Trial Locations

• Breast cancer institute of Fudan University Cancer Hospital, Shanghai, Shanghai Municipality, China

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Advanced Breast Cancer
• Triple Negative Breast Cancer (TNBC)
• HER2-negative Breast Cancer
• Hormone Receptor-positive Breast Cancer
• HER2-positive Breast Cancer
• Metastatic Cancer
• Oncology
• Medical Oncology

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