Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N)

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Breast Tumors; Breast Cancer; Breast Neoplasm; Locally Advanced Breast Cancer; Hormone Receptor Negative Tumor; Early-stage Breast Cancer; Hormone Receptor Positive Tumor; HER2-positive Breast Cancer; HER2-negative Breast Cancer; Triple-Negative Breast Cancer (TNBC)

Treatments: Drug: 9MW2821; Drug: TQB2868; Drug: Fluzoparib; Drug: HRS-4508; Drug: Goserelin; Drug: Ivonescimab; Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Camrelizumab; Drug: JSKN003; Drug: JS207; Drug: HB1801; Drug: SHR-A1811; Drug: Trastuzumab; Drug: Epirubicin; Drug: SHR-A1921; Drug: Apatinib; Drug: SHR-1316; Drug: Carboplatin; Drug: Letrozole; Drug: Benmelstobart; Drug: Dalpiciclib; Drug: SHR-4602; Drug: IBI354; Drug: LEM; Drug: Famitinib; Drug: Anlotinib; Drug: paclitaxel; Drug: Nab paclitaxel; Drug: Pertuzumab; Drug: Pyrotinib; Drug: Cyclophosphamide; Drug: HRS-6209; Drug: TQB2102

Study type: Interventional

Funder types: Other

Identifiers

NCT05582499

FASCINATE-N

Details and patient eligibility

About

The purpose of this study is to establish a prospective, single-center platform research based on clinical subtypes to explore precision neoadjuvant therapy in patients with operable breast cancer who met the indications for neoadjuvant chemotherapy and by the update of basic translational research in the center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs, verified the effectiveness of new targeted drugs in neoadjuvant therapy.

Full description

FASCINATE-N is a platform that will compare the efficacy of novel drugs alone or in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is to identify improved treatment regimens for subsets on the basis of clinical subtyping. In this trial, breast cancer patients eligible for inclusion can be randomly divided into the precision treatment group and conventional neoadjuvant chemotherapy group according to molecular typing and subtyping. 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. As described for previous adaptive trials, regimens that show to be more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.

Enrollment: 716 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed invasive breast cancer of clinical stage T1-4N1-3M0 or cT2-4N0M0;
• Age between18-70 years;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• ER, PR and HER2 status were measured by immunohistochemistry (IHC);
• LVEF≥55%；
• Definition of SNF subtypes: SNF subtypes confirmed by digital pathology of H&E slices;
• Triple negative subtyping: On the basis of triple-negative pathological diagnosis, AR, cluster of differentiation 8 (CD8) and Forkhead Box C1 (FOXC1) were combined to define the subtyping;
• At least one measurable lesion according to RECIST version 1.1
• Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
• Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug;
• Ability to understand and willingness to sign a written informed consent

Exclusion criteria

• Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason;
• Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II);
• Patients with severe systemic infections or other serious diseases;
• Patients with known allergy or intolerance to the study drug or its excipients;
• Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
• Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study;
• Participated in other trial studies within 30 days before the administration of the first dose of the study drug;
• Patients who were judged by the investigator to be unsuitable for this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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716 participants in 63 patient groups

L1-1

Experimental group

Description:

If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype

Treatment:

Drug: Dalpiciclib

Drug: Letrozole

Drug: Goserelin

L1-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF1 subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

L2-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF2 subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

L3-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF3 subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

L4-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF4 subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

L4-low-1

Experimental group

Description:

If patients were HR+HER2-low with SNF4 subtype

Treatment:

Drug: SHR-A1811

L4-low-2

Active Comparator group

Description:

If patients were HR+HER2-low with SNF4 subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

TN1-1

Experimental group

Description:

If patients were triple-negative breast cancer with immunomodulatory (IM) subtype

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

Drug: Camrelizumab

TN1-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with IM subtype

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

TN2-1

Experimental group

Description:

If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

Drug: Fluzoparib

TN2-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with BLIS subtype

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

TN3-1

Experimental group

Description:

If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype

Treatment:

Drug: Cyclophosphamide

Drug: Pyrotinib

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

TN3-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with AR HER2 subtype

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

TN4-1.1

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: SHR-A1811

TN4-2

Active Comparator group

Description:

If patients were HR-HER2-low

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

TN5-1.1

Experimental group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: SHR-A1921

TN5-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

H1-1.1

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: Pyrotinib

Drug: SHR-A1811

H1-2

Active Comparator group

Description:

If patients were HR+HER2+

Treatment:

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Trastuzumab

H2-1.1

Experimental group

Description:

If patients were HR-HER2+

Treatment:

Drug: Pyrotinib

H2-2

Active Comparator group

Description:

If patients were HR-HER2+

Treatment:

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Trastuzumab

L2-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: SHR-1316

L3-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Fluzoparib

L4-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Apatinib

TN5-1.2

Experimental group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: SHR-1316

Drug: SHR-A1921

H1-1.2

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: SHR-A1811

H2-1.2

Experimental group

Description:

If patients were HR-HER2+

Treatment:

Drug: Pyrotinib

Drug: SHR-A1811

TN4-1.2

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: Famitinib

Drug: SHR-A1811

Drug: Camrelizumab

L2-1.1

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype

Treatment:

Drug: Dalpiciclib

Drug: Letrozole

Drug: Goserelin

L2-1.3

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype

Treatment:

Drug: Nab paclitaxel

Drug: Famitinib

Drug: Carboplatin

Drug: SHR-1316

L3-1.1

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype

Treatment:

Drug: Dalpiciclib

Drug: Letrozole

Drug: Goserelin

L4-1.1

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype

Treatment:

Drug: SHR-A1921

L5-1

Experimental group

Description:

If patients were HR+HER2-

Treatment:

Drug: Cyclophosphamide

Drug: LEM

Drug: HB1801

L5-2

Experimental group

Description:

If patients were HR+HER2-

Treatment:

Drug: Cyclophosphamide

Drug: LEM

Drug: HB1801

L6

Experimental group

Description:

If patients were HR+HER2-low

Treatment:

Drug: Famitinib

Drug: SHR-1316

Drug: SHR-A1811

L7

Experimental group

Description:

If patients were HR+HER2-low

Treatment:

Drug: TQB2102

Drug: Famitinib

Drug: Benmelstobart

L8

Experimental group

Description:

If patients were HR+HER2-

Treatment:

Drug: TQB2102

Drug: Anlotinib

Drug: TQB2868

L9

Experimental group

Description:

If patients were HR+HER2-low

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Epirubicin

Drug: Ivonescimab

TN6-1

Experimental group

Description:

TNBC

Treatment:

Drug: Famitinib

Drug: SHR-1316

Drug: SHR-A1811

TN6-2

Experimental group

Description:

TNBC

Treatment:

Drug: SHR-1316

Drug: SHR-A1811

TN7-1

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: TQB2102

Drug: Benmelstobart

TN7-2

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: TQB2102

Drug: Anlotinib

Drug: Benmelstobart

TN8

Experimental group

Description:

TNBC

Treatment:

Drug: TQB2102

Drug: TQB2868

TN9

Experimental group

Description:

TNBC

Treatment:

Drug: Cyclophosphamide

Drug: paclitaxel

Drug: Carboplatin

Drug: Epirubicin

H3

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: JSKN003

H4-1

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Trastuzumab

Drug: SHR-A1811

H4-2

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: SHR-A1811

H4-3

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: Trastuzumab

H4-4

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pyrotinib

Drug: SHR-A1811

H5

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: SHR-4602

Drug: SHR-A1811

H6-1

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: SHR-A1811

Drug: HRS-4508

H6-2

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pertuzumab

Drug: SHR-A1811

Drug: HRS-4508

L10

Experimental group

Description:

If patients were HR+HER2-

Treatment:

Drug: Cyclophosphamide

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: JS207

H8-1

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: HRS-6209

Drug: Letrozole

Drug: SHR-A1811

Drug: Goserelin

H8-2

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: Letrozole

Drug: SHR-A1811

Drug: Goserelin

TN10

Experimental group

Description:

If patients were TNBC

Treatment:

Drug: JS207

Drug: 9MW2821

L11

Experimental group

Description:

If patients were HR+HER2-

Treatment:

Drug: JS207

Drug: 9MW2821

H9

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pertuzumab

Drug: paclitaxel

Drug: Trastuzumab

Drug: SHR-A1811

H10

Experimental group

Description:

If patients were HER2+

Treatment:

Drug: Pertuzumab

Drug: IBI354

TN6-3

Experimental group

Description:

TNBC

Treatment:

Drug: Nab paclitaxel

Drug: Carboplatin

Drug: SHR-1316

Drug: SHR-A1811

TN11-1: TNBC patients predicted sensitive to Paclitaxel+Carboplatin+Camrelizumab+Famitinib by AI

Experimental group

Description:

The TN11 arm explores AI-guided multidisciplinary precision therapy in TNBC. Patients are stratified using an established digital pathology-based AI model that predicts sensitivity to the combination therapy of Paclitaxel, Carboplatin, Camrelizumab and Famitinib. Patients predicted to be sensitive (TN11-1) receive this combination therapy directly.

Treatment:

Drug: paclitaxel

Drug: Famitinib

Drug: Carboplatin

Drug: Camrelizumab

TN11-2: TNBC patients predicted non-sensitive to Paclitaxel+Carboplatin+Camrelizumab+Famitinib by AI

Experimental group

Description:

TNBC patients predicted to be non-sensitive (TN11-2) to the combination therapy of Paclitaxel, Carboplatin, Camrelizumab and Famitinib first undergo stereotactic body radiation therapy (SBRT). SBRT is delivered to the primary tumor in 3 fractions of 8 Gy (total 24 Gy) over 3-5 days. Following SBRT, patients receive the combination therapy of Paclitaxel, Carboplatin, Camrelizumab and Famitinib.

Treatment:

Drug: paclitaxel

Drug: Famitinib

Drug: Carboplatin

Drug: Camrelizumab

Radiation: Stereotactic Body Radiation Therapy (SBRT)

L12

Experimental group

Description:

Patients with HR+HER2- breast cancer, clinical stage cT1c-4, cN0-3, M0, with either tumor grade ≥2 or Ki-67 ≥20%. Patients first undergo stereotactic body radiotherapy (SBRT) to the primary tumor, followed by combination therapy of Paclitaxel + Epirubicin + Cyclophosphamide + Camrelizumab + Famitinib.

Treatment:

Drug: Cyclophosphamide

Drug: paclitaxel

Drug: Famitinib

Drug: Epirubicin

Drug: Camrelizumab

Radiation: Stereotactic Body Radiation Therapy (SBRT)