FUSCC Refractory TNBC Platform Study (FUTURE2.0)

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Triple-negative Breast Cancer

Treatments: Drug: A1: SHR-A1811; Drug: E1: SHR-A1811; Drug: A2: SHR-A1811 with Camrelizumab; Drug: H1: TROP2 ADC; Drug: C2: SHR-A1811 with BP102; Drug: F1: TROP2 ADC; Drug: C1: SHR-A1811; Drug: D1: TROP2 ADC; Drug: B2: TROP2 ADC with Camrelizumab; Drug: D2: TROP2 ADC with BP102; Drug: G1: SHR-A1811; Drug: B1: TROP2 ADC

Study type: Interventional

Funder types: Other

Identifiers

NCT05749588

SCHBCC-N044

Details and patient eligibility

About

This is a Phase II, open-label, Single-center platform study research based on molecular subtypes to explore precision therapy in refractory triple-negative breast cancer.

Full description

This is a Phase II, open-label, Single-center platform study，Based on FUSCC four TNBC subtypes and the results of the previous FUTURE trial, the investigators designed this platform trial, which for combined the TNBC subtyping and genomic sequencing-guided precision targeted therapy for refractory metastatic TNBC patients. In this trial, refractory mTNBC patients eligible for inclusion can be divided into various precision treatment group according to molecular typing and subtyping to evaluate the efficacy and safety of multiple precision targeted treatment. The research therapy arm can be updated with the update of basic translational research in our center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs.

Enrollment: 120 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Female aged ≥18 years;

2. TNBC invasive breast cancer confirmed by histology (specific definition: ER <1% positive tumor cells by immunohistochemistry are defined as ER negative, PR <1% positive tumor cells are defined as PR negative, HER2 0-1+ or HER2 ++ but negative by FISH without amplification was defined as HER2 negative); Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;

3. Progression after at least one prior therapeutic regimens for advanced/metastatic TNBC

4. At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy);

5. 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×ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);

6. 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;

7. ECOG score ≤1, and life expectancy ≥3 months;

8. 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;

9. 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. 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;
5. Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment;
6. Pregnant or lactating patients;
7. Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 8 patient groups

IM/HER2-low

Experimental group

Description:

If patients were triple-negative breast cancer with IM subtype and HER2-low-positive

Treatment:

Drug: A1: SHR-A1811

Drug: A2: SHR-A1811 with Camrelizumab

IM/HER2-0

Experimental group

Description:

If patients were triple-negative breast cancer with IM subtype and HER2-zero

Treatment:

Drug: B2: TROP2 ADC with Camrelizumab

Drug: B1: TROP2 ADC

BLIS / HER2-low

Experimental group

Description:

If patients were triple-negative breast cancer with BLIS subtype and HER2-low-positive

Treatment:

Drug: C1: SHR-A1811

Drug: C2: SHR-A1811 with BP102

BLIS /HER2-0

Experimental group

Description:

If patients were triple-negative breast cancer with BLIS subtype and HER2-zero

Treatment:

Drug: D2: TROP2 ADC with BP102

Drug: D1: TROP2 ADC

LAR / HER2-low

Experimental group

Description:

If patients were triple-negative breast cancer with LAR subtype and HER2-low-positive

Treatment:

Drug: E1: SHR-A1811

LAR /HER2-0

Experimental group

Description:

If patients were triple-negative breast cancer with LAR subtype and HER2-zero

Treatment:

Drug: F1: TROP2 ADC

MES/ HER2-low

Experimental group

Description:

If patients were triple-negative breast cancer with MES subtype and HER2-low-positive

Treatment:

Drug: G1: SHR-A1811

MES /HER2-0

Experimental group

Description:

If patients were triple-negative breast cancer with MES subtype and HER2-zero

Treatment:

Drug: H1: TROP2 ADC