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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Neoplasm; Breast Tumors; HER2-positive Breast Cancer; Locally Advanced Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Positive Tumor; Hormone Receptor Negative Tumor; Early-stage Breast Cancer; Triple-Negative Breast Cancer (TNBC)
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: paclitaxel; Drug: Trastuzumab; Drug: Dalpiciclib; Drug: Goserelin; Drug: Letrozole; Drug: Nab paclitaxel; Drug: Carboplatin; Drug: SHR-1316; Drug: Fluzoparib; Drug: SHR-A1811; Drug: Camrelizumab; Drug: Epirubicin; Drug: Pyrotinib; Drug: Pertuzumab; Drug: SHR-A1921; Drug: Apatinib; Drug: Famitinib; Drug: HB1801; Drug: LEM; Drug: TQB2102; Drug: Benmelstobart; Drug: Anlotinib; Drug: TQB2868; Drug: Ivonescimab; Drug: JSKN003; Drug: SHR-4602; Drug: HRS-4508; Drug: JS207

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 716
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimin Shao, Professor; Phone Number: +86(021)64175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center Shanghai, China, 200032
      • Contact: Zhimin Shao, M.D.; Phone Number: 88807 +86-021-64175590; Email: zhimingshao@yahoo.com
      • Contact: Min He, M.D; Phone Number: 88603 +86-021-64175590; Email: minsmiler@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed invasive cancer of the breast and meet the clinical stage II（T2N0-1M0/T3N0M0）or III（T2N2M0/T3N1-2M0) criteria;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

53

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L1-1; If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype	Drug: Dalpiciclib; an oral cyclin-dependent kinases (CDK) 4/6 inhibitor; Other Names: SHR-6390; Drug: Goserelin; goserelin; Drug: Letrozole; letrozole
Active Comparator: L1-2; If patients were HR+HER2- with SNF1 subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin
Active Comparator: L2-2; If patients were HR+HER2- with SNF2 subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin
Active Comparator: L3-2; If patients were HR+HER2- with SNF3 subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin
Active Comparator: L4-2; If patients were HR+HER2- with SNF4 subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin
Experimental: L4-low-1; If patients were HR+HER2-low with SNF4 subtype	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC)
Active Comparator: L4-low-2; If patients were HR+HER2-low with SNF4 subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin
Experimental: TN1-1; If patients were triple-negative breast cancer with immunomodulatory (IM) subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Camrelizumab; an anti-programmed death-1 (PD1) antibody; Other Names: SHR-1210; Drug: Epirubicin; Epirubicin
Active Comparator: TN1-2; If patients were triple-negative breast cancer with IM subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Experimental: TN2-1; If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Fluzoparib; an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor; Other Names: SHR-3162; Drug: Epirubicin; Epirubicin
Active Comparator: TN2-2; If patients were triple-negative breast cancer with BLIS subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Experimental: TN3-1; If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin; Drug: Pyrotinib; an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Active Comparator: TN3-2; If patients were triple-negative breast cancer with AR HER2 subtype	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Active Comparator: TN4-2; If patients were HR-HER2-low	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Active Comparator: TN5-2; If patients were triple-negative breast cancer with other subtypes	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Active Comparator: H1-2; If patients were HR+HER2+	Drug: Trastuzumab; Trastuzumab; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Pertuzumab; Pertuzumab
Active Comparator: H2-2; If patients were HR-HER2+	Drug: Trastuzumab; Trastuzumab; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Pertuzumab; Pertuzumab
Experimental: L2-1.1; If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype	Drug: Dalpiciclib; an oral cyclin-dependent kinases (CDK) 4/6 inhibitor; Other Names: SHR-6390; Drug: Goserelin; goserelin; Drug: Letrozole; letrozole
Experimental: L3-1.1; If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype	Drug: Dalpiciclib; an oral cyclin-dependent kinases (CDK) 4/6 inhibitor; Other Names: SHR-6390; Drug: Goserelin; goserelin; Drug: Letrozole; letrozole
Experimental: L4-1.1; If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype	Drug: SHR-A1921; Trophoblast cell-surface antigen 2 (TROP2) ADC
Experimental: TN4-1.1; If patients were HR-HER2-low	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC)
Experimental: TN5-1.1; If patients were triple-negative breast cancer with other subtypes	Drug: SHR-A1921; Trophoblast cell-surface antigen 2 (TROP2) ADC
Experimental: H1-1.1; If patients were HR+HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Pyrotinib; an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Experimental: H2-1.1; If patients were HR-HER2+	Drug: Pyrotinib; an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Experimental: L2-1.2; If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody
Experimental: L3-1.2; If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Fluzoparib; an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor; Other Names: SHR-3162
Experimental: L4-1.2; If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Apatinib; tyrosine kinase inhibitors
Experimental: TN5-1.2; If patients were triple-negative breast cancer with other subtypes	Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody; Drug: SHR-A1921; Trophoblast cell-surface antigen 2 (TROP2) ADC
Experimental: H1-1.2; If patients were HR+HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC)
Experimental: H2-1.2; If patients were HR-HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Pyrotinib; an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Experimental: TN4-1.2; If patients were HR-HER2-low	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Camrelizumab; an anti-programmed death-1 (PD1) antibody; Other Names: SHR-1210; Drug: Famitinib; tyrosine kinase inhibitors
Experimental: L2-1.3; If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype	Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody; Drug: Famitinib; tyrosine kinase inhibitors
Experimental: L5-1; If patients were HR+HER2-	Drug: Cyclophosphamide; Cyclophosphamide; Drug: HB1801; Albumin docetaxel; Drug: LEM; liposome-entrapped mitoxantrone
Experimental: L5-2; If patients were HR+HER2-	Drug: Cyclophosphamide; Cyclophosphamide; Drug: HB1801; Albumin docetaxel; Drug: LEM; liposome-entrapped mitoxantrone
Experimental: L6; If patients were HR+HER2-low	Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody; Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Famitinib; tyrosine kinase inhibitors
Experimental: L7; If patients were HR+HER2-low	Drug: Famitinib; tyrosine kinase inhibitors; Drug: TQB2102; an anti-HER2 ADC; Drug: Benmelstobart; an anti-PDL1 antibody
Experimental: L8; If patients were HR+HER2-	Drug: TQB2102; an anti-HER2 ADC; Drug: Anlotinib; an tyrosine kinase inhibitor; Drug: TQB2868; anti-PD-1/TGF-βRII
Experimental: L9; If patients were HR+HER2-low	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin; Drug: Ivonescimab; an anti-PD-1/VEGF bispecific antibody
Experimental: TN6-1; TNBC	Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody; Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Famitinib; tyrosine kinase inhibitors
Experimental: TN6-2; TNBC	Drug: SHR-1316; an anti-programmed death ligand 1 (PD-L1) antibody; Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC)
Experimental: TN7-1; If patients were HR-HER2-low	Drug: TQB2102; an anti-HER2 ADC; Drug: Benmelstobart; an anti-PDL1 antibody
Experimental: TN7-2; If patients were HR-HER2-low	Drug: TQB2102; an anti-HER2 ADC; Drug: Benmelstobart; an anti-PDL1 antibody; Drug: Anlotinib; an tyrosine kinase inhibitor
Experimental: TN8; TNBC	Drug: TQB2102; an anti-HER2 ADC; Drug: TQB2868; anti-PD-1/TGF-βRII
Experimental: TN9; TNBC	Drug: Cyclophosphamide; Cyclophosphamide; Drug: paclitaxel; paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Epirubicin; Epirubicin
Experimental: H3; If patients were HER2+	Drug: JSKN003; an anti-HER2 ADC
Experimental: H4-1; If patients were HER2+	Drug: Trastuzumab; Trastuzumab; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Pertuzumab; Pertuzumab
Experimental: H4-2; If patients were HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC)
Experimental: H4-3; If patients were HER2+	Drug: Trastuzumab; Trastuzumab; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Carboplatin; Carboplatin; Drug: Pertuzumab; Pertuzumab
Experimental: H4-4; If patients were HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Pyrotinib; an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Experimental: H5; If patients were HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: SHR-4602; an anti-HER2 ADC
Experimental: H6-1; If patients were HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: HRS-4508; an HER2 inhibitor
Experimental: H6-2; If patients were HER2+	Drug: SHR-A1811; an anti-HER2 antibody-drug conjugate (ADC); Drug: Pertuzumab; Pertuzumab; Drug: HRS-4508; an HER2 inhibitor
Experimental: L10; If patients were HR+HER2-	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Nab paclitaxel; Albumin paclitaxel; Drug: Epirubicin; Epirubicin; Drug: JS207; an anti-PD-1/VEGF bispecific antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	Pathological complete response rate	through study completion, up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
invasive disease-free survival (iDFS)	To determine three-year invasive disease-free survival (iDFS) among the treatment arms	Three-year Post-surgery Follow-up
Overall response rate (ORR)	Complete response (CR) + partial response (PR)	up to 24 weeks
CTCAE scale (V4.0)	4) To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)	through study completion, an average of 1 year
Evaluate gene expression profile during treatment	To measure gene expression profile of baseline and sequential tumor samples during treatment, through RNA-seq platform	through study completion, up to 24 weeks
Number of peripheral blood mononuclear cells (PBMC) count during treatment	To measure number of peripheral blood mononuclear cells (PBMC) count from baseline and sequential blood samples during treatment, through Flow CytoMetry platform	through study completion, up to 24 weeks

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhimin Shao, Professor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 25, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Steroid Synthesis Inhibitors; Hormone Antagonists; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Estrogen Antagonists; Aromatase Inhibitors; Trastuzumab; Letrozole; Albumin-Bound Paclitaxel; Fluzoparib; Cyclophosphamide; Carboplatin; Paclitaxel; Pertuzumab; Goserelin; Epirubicin; Apatinib
• Other Study ID Numbers: FASCINATE-N

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No