ClinicalTrials.gg
RecruitingNCT01042379I-SPYUpdated May 6, 2026

I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

A Phase 2 interventional study of Standard Therapy and AMG 386 with or without Trastuzumab in Breast Neoplasms, Breast Cancer and Breast Tumors, sponsored by QuantumLeap Healthcare Collaborative. Recruiting at 42 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.

Primary conditionTriple Negative Breast NeoplasmsRegistry: Breast NeoplasmsReclassifiedWhy we changed it
Registry
Breast Neoplasms — the first condition term the registry derived for this study.
ClinicalTrials.gg
Triple Negative Breast Neoplasms
Why
  1. The study's listed conditions name Triple Negative Breast Neoplasms, a narrower term within Breast Neoplasms.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by QuantumLeap Healthcare Collaborative · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2010; still recruiting 16 years 8 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
5,000
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success.

Read the detailed description

I-SPY2 will assess the efficacy of novel drugs in sequence with standard chemotherapy. The goal is identify treatment strategies for subsets on the basis of molecular characteristics (biomarker signatures) of their disease with high estimated pCR rate. As described for previous adaptive trials, novel regimens with sufficiently high activities alone and contribute to treatment strategies that show a high Bayesian predictive probability of being more effective than the dynamic control will graduate from the trial with their corresponding biomarker signature(s). Treatment strategies 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.

02

Conditions studied

  • Breast Neoplasms
  • Breast Cancer
  • Breast Tumors
  • Angiosarcoma
  • TNBC - Triple-Negative Breast Cancer
  • HER2-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Hormone Receptor Positive Tumor
  • Hormone Receptor Negative Tumor
  • Early-stage Breast Cancer
  • Locally Advanced Breast Cancer

Keywords

  • Neoadjuvant
  • Breast
  • Cancer
  • Neoplasm
  • Adaptive
  • pCR
  • Pathologic Complete Response
  • Biomarkers signature
  • MRI Volume
  • Endocrine Therapy
  • Chemotherapy
  • Immunotherapy
03

In context

Triple Negative Breast Neoplasms Reclassified

1,219 studies on the registry are indexed under Triple Negative Breast Neoplasms; 446 are open to participants now.

This study's planned enrollment of 5,000 is above the median of 60 across 1,053 interventional studies indexed under Triple Negative Breast Neoplasms.

Browse Triple Negative Breast Neoplasms studies →

Lead sponsor

QuantumLeap Healthcare Collaborative is the lead sponsor of 5 studies on the registry; 3 are open to participants now.

Compared within Triple Negative Breast Neoplasms, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Breast Neoplasms. The counts are of registry records indexed under each term, refreshed daily. How we classify →

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • confirmed invasive cancer of the breast
  • Clinically or radiologically measureable disease in the breast after diagnostic , defined as longest diameter greater than or equal to 25 mm (2.5cm)
  • No prior cytotoxic regimens are allowed for this . Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
  • Age ≥18 years
  • performance status 0-1
  • Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
  • Non-pregnant and non-lactating
  • No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible.
  • Ability to understand and willingness to sign a written (I-SPY TRIAL Screening Consent)
  • Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites
  • Any tumor ER/PgR status, any /neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F
  • Normal organ and marrow function: Leukocytes ≥ 3000/μL, ≥ 1500/μL, ≥ 100,000/μL, Total within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x , (SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine \< 1.5 x institutional ULN
  • No uncontrolled or severe cardiac disease. Baseline (by nuclear imaging or echocardiography) must by ≥ 50%
  • No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
  • Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (\<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™)
  • Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2)

Exclusion criteria

Exclusion Criteria:

  • Use of any other agents within 30 days of starting study treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Terms in these criteria, in plain language(14)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

HER2

HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.

In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
5,000 participants (estimated)

Study arms

  • Active comparator
    Standard Therapy

    Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.

    Drug: Standard Therapy

  • Experimental
    AMG 386 with or without Trastuzumab

    Arm is closed.

    Drug: AMG 386 with or without Trastuzumab · Drug: AMG 386 and Trastuzumab

  • Other
    AMG 479 plus Metformin

    Arm is closed.

    Drug: AMG 479 (Ganitumab) plus Metformin

  • Experimental
    MK-2206 with or without Trastuzumab

    Arm is closed.

    Drug: MK-2206 with or without Trastuzumab

  • Experimental
    T-DM1 and Pertuzumab

    Arm is closed.

    Drug: T-DM1 and Pertuzumab

  • Active comparator
    Pertuzumab and Trastuzumab

    Arm is closed. Novel Control Investigational Agent.

    Drug: Pertuzumab and Trastuzumab

  • Experimental
    Ganetespib

    Arm is closed.

    Drug: Ganetespib

  • Other
    ABT-888

    Arm is closed.

    Drug: ABT-888

  • Other
    Neratinib

    Arm is closed.

    Drug: Neratinib

  • Experimental
    PLX3397

    Arm is closed.

    Drug: PLX3397

  • Experimental
    Pembrolizumab 4 cycle

    Arm is closed.

    Drug: Pembrolizumab - 4 cycle

  • Experimental
    Talazoparib plus Irinotecan

    Arm is closed.

    Drug: Talazoparib plus Irinotecan

  • Experimental
    Patritumab with or without Trastuzumab

    Arm is closed.

    Drug: Patritumab and Trastuzumab

  • Experimental
    Pembrolizumab 8 cycle

    Arm is closed.

    Drug: Pembrolizumab - 8 cycle

  • Experimental
    SGN-LIV1A

    Arm is closed.

    Drug: SGN-LIV1A

  • Experimental
    Durvalumab plus Olaparib

    Arm is closed.

    Drug: Durvalumab plus Olaparib

  • Experimental
    SD-101 + Pembrolizumab

    Arm is closed.

    Drug: SD-101 + Pembrolizumab

  • Experimental
    Tucatinib

    Arm is closed.

    Drug: Tucatinib plus trastuzumab and pertuzumab

  • Experimental
    Cemiplimab

    Arm is closed. Novel Investigational Agent.

    Drug: Cemiplimab

  • Experimental
    Cemiplimab plus REGN3767

    Arm is closed. Novel Investigational Agent.

    Drug: Cemiplimab plus REGN3767

  • Experimental
    Trilaciclib with or without trastuzumab + pertuzumab

    Arm is closed. Novel Investigational Agent.

    Drug: Trilaciclib with or without trastuzumab + pertuzumab

  • Experimental
    SYD985 ([vic-]trastuzumab duocarmazine)

    Arm is closed. Novel Investigational Agent.

    Drug: SYD985 ([vic-]trastuzumab duocarmazine)

  • Experimental
    Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab

    Arm is closed. Novel Investigational Agent.

    Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab

  • Experimental
    Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab

    Arm is closed. Novel Investigational Agent.

    Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab

  • Experimental
    Endocrine Optimization Pilot: Amcenestrant Monotherapy

    Arm is closed. Novel Investigational Agent.

    Drug: Amcenestrant

  • Experimental
    Endocrine Optimization Pilot: Amcenestrant + Abemaciclib

    Arm is closed. Novel Investigational Agent.

    Drug: Amcenestrant + Abemaciclib

  • Experimental
    Endocrine Optimization Pilot: Amcenestrant + Letrozole

    Arm is closed. Novel Investigational Agent.

    Drug: Amcenestrant + Letrozole

  • Experimental
    ARX788 in Block A and followed by SOC in Block B

    Arm is closed for accrual for accrual. Novel investigational Agent followed by SOC.

    Drug: ARX788

  • Experimental
    ARX788 + Cemiplimab in Block A and followed by SOC in Block B

    Arm is closed for accrual. Novel investigational Agent followed by SOC.

    Drug: ARX788 + Cemiplimab

  • Experimental
    VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B

    Arm is closed for accrual. Novel investigational Agent followed by SOC.

    Drug: VV1 + Cemiplimab

  • Experimental
    Datopotamab Deruxtecan in Block A and followed by SOC in block B

    Arm is closed for accrual. Novel investigational Agent followed by SOC.

    Drug: Datopotamab deruxtecan

  • Experimental
    Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B

    Arm is closed for accrual. Novel investigational Agent followed by SOC.

    Drug: Datopotamab deruxtecan + Durvalumab

  • Experimental
    Zanidatamab for Block ABC

    Arm open for accrual. Novel investigational Agent.

    Drug: Zanidatamab

  • Experimental
    Endocrine Optimization Pilot: Lasofoxifene

    Arm is closed for accrual. Novel investigational Agent.

    Drug: Lasofoxifene

  • Experimental
    Endocrine Optimization Pilot: (Z)-Endoxifen

    Arm is closed for accrual. Novel investigational Agent.

    Drug: Z-endoxifen

  • Experimental
    Endocrine Optimization Pilot: ARV-471

    Arm is closed for accrual. Novel investigational Agent.

    Drug: ARV-471

  • Experimental
    Endocrine Optimization Pilot: ARV-471 + Letrozole

    Arm is closed for accrual. Novel investigational Agent.

    Drug: ARV-471 + Letrozole

  • Experimental
    Endocrine Optimization Pilot: ARV-471 + Abemaciclib

    Arm is closed for accrual. Novel investigational Agent.

    Drug: ARV-471 + Abemaciclib

  • Experimental
    Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib

    Arm is closed for accrual. Enrollment completed. Novel investigational Agent.

    Drug: Endoxifen + Abemaciclib

  • Experimental
    Rilvegostomig + TDXd in Block A and followed by SOC in Block B

    Arm is closed for accrual. Novel investigational Agent.

    Drug: Rilvegostomig + TDXd

  • Experimental
    DAN222 + Niraparib in Block A and followed by SOC in Block B

    Arm is closed for accrual. Novel investigational Agent.

    Drug: Dan222 + Niraparib

  • Experimental
    Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block C

    Arm is closed for accrual. Novel investigational Agent.

    Drug: Sarilumab + Cemiplimab + Paclitaxel

  • Experimental
    GSK 5733584 in Block A and followed by SOC in Block B

    Arm is open for accrual. Novel Investigational Agent.

    Drug: GSK 5733584

  • Experimental
    GSK 5733584 + Dostarlimab in Block A and followed by SOC in Block B

    Arm is open for accrual. Novel Investigational Agent.

    Drug: GSK 5733584 + Dostarlimab

  • Experimental
    Ivonescimab in Blocks A and B

    Open for accrual. Novel Investigational Agent.

    Drug: Ivonescimab (20mg/kg Q3W)

Interventions

  • DrugStandard Therapy

    Paclitaxel: 80 mg/m2 IV during the 12 weekly treatment cycles post randomization; Doxorubicin: 60 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16; Cyclophosphamide: 600 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16

    Also known as: Paclitaxel (Taxol); Doxorubicin (Adriamycin)

  • DrugAMG 386 with or without Trastuzumab

    Drug pages: Trebananib · Trastuzumab

    Arm is closed.

    Also known as: AMG 386 (Trebananib); (Trastuzumab) Herceptin

  • DrugAMG 479 (Ganitumab) plus Metformin

    Drug page: Ganitumab

    Arm is closed.

    Also known as: Ganitumab

  • DrugMK-2206 with or without Trastuzumab

    Drug pages: MK 2206 · Trastuzumab

    Arm is closed.

    Also known as: (Trastuzumab) Herceptin

  • DrugAMG 386 and Trastuzumab

    Drug pages: Trebananib · Trastuzumab

    Arm is closed.

    Also known as: AMG 386 (Trebananib); Trastuzumab (Herceptin)

  • DrugT-DM1 and Pertuzumab

    Drug pages: Ado-Trastuzumab Emtansine · Pertuzumab

    Arm is closed.

    Also known as: T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)

  • DrugPertuzumab and Trastuzumab

    Arm is closed for Accrual. Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization

    Also known as: Pertuzumab (Perjeta); Trastuzumab (Herceptin)

  • Arm is closed.

  • Arm is closed.

    Also known as: Veliparib

  • Arm is closed.

  • Arm is closed.

  • Arm is closed.

  • DrugTalazoparib plus Irinotecan

    Drug pages: Talazoparib · Irinotecan

    Arm is closed.

  • DrugPatritumab and Trastuzumab

    Drug pages: Patritumab · Trastuzumab

    Arm is closed.

  • Arm is closed.

  • Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16

  • DrugDurvalumab plus Olaparib

    Drug pages: Durvalumab · Olaparib

    Arm is closed.

  • DrugSD-101 + Pembrolizumab

    Drug pages: Nelitolimod · Pembrolizumab

    Arm is closed. SD-101: IT injection 2 mg/ml (1 ml for T2 tumors, 2 ml for \>T3 tumors) weekly x 4, then every 3 weeks x 2 cycles 1,2,3,4,7,10 Pembrolizumab: 200mg IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

  • DrugTucatinib plus trastuzumab and pertuzumab

    Drug pages: Tucatinib · Trastuzumab · Pertuzumab

    Arm is closed. Tucatinib: 300 mg PO BID 12 weeks CLOSED Tucatinib: 250 mg PO BID 12 weeks CLOSED Tucatinib adaptive: 150mg BID days 1-28, 250mg BID days 29-84 Trastuzumab: 4 mg/kg IV (loading dose) cycle 1; 2 mg/kg (thereafter) cycles 2-12 Pertuzumab: 840 mg IV (loading dose) cycle 1; 420 mg (thereafter) cycles 4, 7 and 10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

  • Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

  • DrugCemiplimab plus REGN3767

    Drug pages: Cemiplimab · Fianlimab

    Arm is closed. Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 REGN 3767: 1600 mg q3W X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

  • DrugTrilaciclib with or without trastuzumab + pertuzumab

    Drug pages: Trilaciclib · Trastuzumab · Pertuzumab

    Arm closed for accrual. Trilaciclib: 240 mg/m2 IV weekly cycle 1-16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles For HER2+: Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization

    Also known as: Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)

  • Arm is closed. SYD985: 1.2 mg/kg IV (q3w x 12 weeks) cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

  • DrugOral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab

    Drug page: Dostarlimab

    Arm is closed. For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    Also known as: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

  • DrugOral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab

    Drug page: Dostarlimab

    Arm is closed. For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    Also known as: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

  • Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks.

    Also known as: SAR439859

  • DrugAmcenestrant + Abemaciclib

    Drug pages: Amcenestrant · Abemaciclib

    Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks

    Also known as: Amcenestrant (SAR439859), Abemaciclib (Verzenio)

  • DrugAmcenestrant + Letrozole

    Drug pages: Amcenestrant · Letrozole

    Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks

    Also known as: Amcenestrant (SAR439859), Letrozole (Femara)

  • DrugARX788

    Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks

  • DrugARX788 + Cemiplimab

    Drug pages: ARX788 · Cemiplimab

    Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks

  • DrugVV1 + Cemiplimab

    Arm is closed. VV1, 3x10\^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks

    Also known as: VOYAGER V1™, VSV-IFNβ-NIS

  • Arm is closed. Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks

    Also known as: Dato-DXd

  • DrugDatopotamab deruxtecan + Durvalumab

    Drug pages: Datopotamab deruxtecan · Durvalumab

    Arm is closed. Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks

    Also known as: Dato-DXd

  • Zanidatamab: IV Infusion at a 2-tiered flat dose. 1,800mg (\<70 kg) and 2400mg (≥70 kg). Neoadjuvant doing of zanidatamab: The initial dose will be administered on Cycle 1 Day 1, with Cycle 2 Day 1 occurring 14 days thereafter, followed by subsequent dosing every 3 weeks (Q3W) for a total of up to 5 doses in block A, up to 4 doses Block B, up to 5 doses Block C. Adjuvant dosing of zanidatamab: Administered every 3 weeks (Q3W) for a total of 1 year of HER2 based therapy. The total number of adjuvant weeks will be dependent on the number of weeks of exposure of zanidatamab in Blocks A, B, and C.

  • Arm is closed. Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks

  • Arm is closed. Z-endoxifen: 10 mg QD, p.o., for 24 weeks

  • Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks.

  • DrugARV-471 + Letrozole

    Drug pages: Vepdegestrant · Letrozole

    Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks

  • DrugARV-471 + Abemaciclib

    Drug pages: Vepdegestrant · Abemaciclib

    Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks Abemaciclib: 150 mg BID, p.o, for 24 weeks

  • DrugEndoxifen + Abemaciclib

    Drug pages: Endoxifen · Abemaciclib

    Z-endoxifen: 80 mg QD, p.o., for 24 weeks Abemaciclib: 150 mg BID, p.o, for 20 weeks

  • DrugRilvegostomig + TDXd

    Drug page: Rilvegostomig

    Arm closed to accrual Rilvegostomig: 750mg IV Q3W for 12 weeks TDXd: 5.4 mg/kg IV Q3W for 12 weeks

  • DrugDan222 + Niraparib

    Drug page: Niraparib

    Arm is closed. DAN222: 8mg/m2 IV QW for 12 weeks Niraparib: 200mg QD p.p., 12 weeks

  • DrugSarilumab + Cemiplimab + Paclitaxel

    Drug pages: Sarilumab · Cemiplimab · Paclitaxel

    Arm is closed to accrual. Sarilumab: 200mg Subcutaneous injection Q2W for 12 weeks Cemiplimab: 350mg IV Q3W for 12 weeks Paclitaxel: 80 mg/m2 IV QW for 12 weeks

  • Arm is open for accrual. Route: Intravenous infusion Dosage Form: 4.8 mg/kg intravenous Q3W for injection. Will receive a max of 12 weeks.

  • DrugGSK 5733584 + Dostarlimab

    Drug pages: Mocertatug rezetecan · Dostarlimab

    Arm is open for accrual. GSK 5733584 Route: Intravenous Infusion Dosage Form: 4.8 mg/kg intravenous Q3W for injection x 12 weeks max. Dostarlimab Route: Intravenous Infusion Dosage Form: 500 mg fixed dose intravenous Q3W for infusion x 12 weeks max.

  • DrugIvonescimab (20mg/kg Q3W)

    Drug page: Ivonescimab

    Strengths to be used in trial: 1. 20 mg/kg IV Q3W monotherapy 2. 20 mg/kg IV Q3W with paclitaxel 3. 20 mg/kg IV Q3W with carboplatin and paclitaxel. Standard Regimen: 20 mg/kg IV Q3W. Patients in Block A will receive a minimum of 6 weeks a maximum of 12 weeks of Ivonescimab monotherapy in Block A. Patients that have completed Block A, may receive ivonescimab plus paclitaxel or ivonescimab plus paclitaxel plus carboplatin in Block B (depending on subtype).

    Also known as: AK112, SMT112, PD-1 / VEGF bispecific antibody, 依达方® (Yiwoxi Dankang Zhusheye)

This study also gives Trastuzumab deruxtecan. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

Primary outcomes

  1. Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.

    Time frame: Post surgery based on upto 36-week treatment

Secondary outcomes

  1. Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).

    Time frame: Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery

  2. To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.

    Time frame: Three- and Five-Year Post-surgery Follow-up

  3. To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.

    Time frame: Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up

  4. MRI Volume

    Time frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery

07

Study locations

32 of 42 sites recruiting
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
    Recruiting
    • Erica Stringer-Reasor, MD · Principal investigator
  • Mayo Clinic - Scottsdale
    Scottsdale, Arizona 85259, United States
    Not yet recruiting
    • · Contact507-538-7623
    • Donald Northfelt, MD · Principal investigator
  • University of Arizona
    Tucson, Arizona 85724, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • University of California - Davis, Comprehensive Cancer Center
    Davis, California 95817, United States
    Recruiting
    • Mili Arora, MD · Principal investigator
  • City of Hope
    Duarte, California 91010, United States
    Recruiting
    • · Contact800-826-4673
    • Hope Rugo, MD · Principal investigator
  • University of California San Diego
    La Jolla, California 92093-0698, United States
    Recruiting
    • · Contact858-822-6194
    • · ContactCancerCTO@ucsd.edu · 858-822-6194
    • Anne Wallace, MD · Principal investigator
  • University of Southern California
    Los Angeles, California 90033, United States
    Recruiting
    • Kristy Watkins, RN · ContactWatkins_K@ccnt.usc.edu · 323-865-0452
    • Evanthia Roussos Torres, MD · Principal investigator
  • HOAG Memorial Hospital Presbyterian
    Newport Beach, California 92663, United States
    Recruiting
    • Chaitali Nangia, MD · Principal investigator
  • University of California San Francisco (UCSF)
    San Francisco, California 94115, United States
    Recruiting
    • Clinical Research Coordinator · Contactispycrc@ucsf.edu · 415-443-4296
    • Amy Jo Chien, MD · Principal investigator
  • University of Colorado Cancer Center
    Aurora, Colorado 80045, United States
    Recruiting
    • · Contact720-848-1622
    • Anthony Elias, MD · Sub investigator
    • Virgnia Borges, MD · Principal investigator
  • Yale Cancer Center
    New Haven, Connecticut 06510, United States
    Recruiting
    • Trisha Burello, MS · Contacttrisha.burrello@yale.edu · 203-737-2848
    • Tara Snaft, MD · Sub investigator
    • Lajos Pusztai, MD · Sub investigator
    • Mariya Rozenblit, MD · Principal investigator
  • Georgetown University Medical Center
    Washington D.C., District of Columbia 20007, United States
    Recruiting
    • Minetta Liu, MD · ContactLiumc@georgetown.edu · 202-444-3677
    • Claudine Isaacs, MD · Principal investigator
  • H. Lee Moffitt Cancer Center and Research Institute
    Tampa, Florida 33612, United States
    Recruiting
    • Hyo Heather Han, MD · Principal investigator
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
    Recruiting
    • Heather Han, MD · Principal investigator
  • Winship Cancer Institute of Emory University
    Atlanta, Georgia 30322, United States
    Recruiting
    • Kevin Kalinsky, MD · Principal investigator
  • University of Chicago
    Chicago, Illinois 60453, United States
    Recruiting
    • · Contact773-834-2756
    • Rita Nanda, MD · Principal investigator
  • Loyola University
    Maywood, Illinois 60153, United States
    Recruiting
    • · Contact708-327-3102
    • Kathy S Albain, MD · Principal investigator
  • University of Kansas
    Westwood, Kansas 66205, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • Herbert-Herman Cancer Center, Sparrow Hospital
    Lansing, Michigan 48912, United States
    Recruiting
    • Brittani Thomas, DO · Principal investigator
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
    Recruiting
    • · Contact612-626-8487
    • Douglas Yee, MD · Principal investigator
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
    Recruiting
    • · Contact507-538-7623
    • Judy C Boughey, MD · Principal investigator
  • Metro Minnesota Community Oncology Research Consortium, Hennepin County Medical Center
    Saint Louis Park, Minnesota 55416, United States
    Recruiting
    • Satya Bommakanti, MD · Principal investigator
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey 08903, United States
    Recruiting
    • · Contact732-235-7356
    • Coral Omene, MD, PhD · Principal investigator
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
    Recruiting
    • Ellis Levine, MD · Principal investigator
  • Laura and Isaac Perlmutter Cancer Center / NYU Langone Health
    New York, New York 10016, United States
    Recruiting
  • Columbia University Medical Center
    New York, New York 10032, United States
    Recruiting
    • Meghana Trivedi, MD · Principal investigator
  • University of Rochester Wilmot Cancer Institute
    Rochester, New York 14642, United States
    Recruiting
  • Montefiore Medical Center
    The Bronx, New York 10467, United States
    Recruiting
    • Jesus D Anampa · Principal investigator
  • Wake Forest Baptist Comprehensive Cancer Center
    Winston-Salem, North Carolina 27157, United States
    Recruiting
    • Angela Howell, MD · Contactanhowell@wakehealth.edu · 336-716-5440
    • Marissa Howard-McNatt, MD · Principal investigator
  • Cleveland Clinic
    Cleveland, Ohio 44106, United States
    Recruiting
    • · Contact800-233-2273
    • Julie Lang, MD · Principal investigator
  • The Ohio State University, Stefanie Spielman Comprehensive Breast Center
    Columbus, Ohio 43212, United States
    Recruiting
    • Nicole Williams, MD · Principal investigator
  • Oregon Health & Science Institute (OHSU)
    Portland, Oregon 97239, United States
    Recruiting
    • Brienna Palm · Contactpalmb@ohsu.edu · 503-494-4438
    • · Contact503-494-8573
    • Alexandra Zimmer, MD · Principal investigator
  • University of Pennsylvania (U Penn)
    Philadelphia, Pennsylvania 19104, United States
    Recruiting
    • · Contact215-614-1850
    • Amy Clark, MD · Principal investigator
  • University Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15213, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • Sanford Clinical Research
    Sioux Falls, South Dakota 57104, United States
    Recruiting
    • Amy Sanford, MD · Principal investigator
  • Vanderbilt University Medical Center
    Nashville, Tennessee 27204, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • University of Texas, Southwestern Medical Center
    Dallas, Texas 75390-9155, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • University of Texas, M.D. Anderson Cancer Center
    Houston, Texas 77230-1439, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • Huntsman Cancer Institute, University of Utah
    Salt Lake City, Utah 84112, United States
    Recruiting
    • Christos Vaklavas, MD · Principal investigator
  • Inova Health System
    Falls Church, Virginia 22042, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • Swedish Cancer Institute
    Seattle, Washington 98104, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

  • University of Washington
    Seattle, Washington 98115, United States
    Active, not recruiting

    Not enrolling at this site — choose another above.

08

References and documents

Publications

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  • Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, van 't Veer L, Hylton N. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012 Sep 10;30(26):3242-9. doi: 10.1200/JCO.2011.39.2779. Epub 2012 May 29. PubMed 22649152 ↗
  • Hylton NM, Blume JD, Bernreuter WK, Pisano ED, Rosen MA, Morris EA, Weatherall PT, Lehman CD, Newstead GM, Polin S, Marques HS, Esserman LJ, Schnall MD; ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012 Jun;263(3):663-72. doi: 10.1148/radiol.12110748. PubMed 22623692 ↗
  • Lin C, Buxton MB, Moore D, Krontiras H, Carey L, DeMichele A, Montgomery L, Tripathy D, Lehman C, Liu M, Olapade O, Yau C, Berry D, Esserman LJ; I-SPY TRIAL Investigators. Locally advanced breast cancers are more likely to present as Interval Cancers: results from the I-SPY 1 TRIAL (CALGB 150007/150012, ACRIN 6657, InterSPORE Trial). Breast Cancer Res Treat. 2012 Apr;132(3):871-9. doi: 10.1007/s10549-011-1670-4. Epub 2011 Jul 28. PubMed 21796368 ↗
  • Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, DeMichele A, Gray JW, Conway-Dorsey K, Lenburg ME, Buxton MB, Davis SE, van't Veer LJ, Hudis C, Chin K, Wolf D, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Livasy C, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, Au A, Hylton N; I-SPY 1 TRIAL Investigators. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012 Apr;132(3):1049-62. doi: 10.1007/s10549-011-1895-2. Epub 2011 Dec 25. PubMed 22198468 ↗
  • Isaacs C, Nanda R, Yau C, Chien AJ, Hershman DL, Stringer-Reasor EM, Wallace AM, Thomas A, Vaklavas C, Clark AS, Kennedy LC, Sanford A, Boughey JC, Albain KS, Pusztai L, Kalinsky KM, Beckwith H, Williams NO, Han HS, Falkson C, Arora M, Elias AD, Pohlmann PR, Rozenblit M, Marshall N, Chen YY, Trivedi MS, McGuinness JE, Howard FM, Chen N, Khoury K, Lancaster RB, Yeung KT, Douglas E, Wei M, Mainor C, LeStage B, Delson AL, Asare AL, Brown-Swigart L, Hirst GL, Matthews JB, Perlmutter J, Symmans WF, Yee D, Hylton NM, van 't Veer LJ, Rugo HS, DeMichele AM, Berry DA, Esserman LJ. Cemiplimab and Fianlimab With Neoadjuvant Chemotherapy in Early-Stage High-Risk ERBB2-Negative Breast Cancer: The I-SPY2 Randomized Clinical Trial. JAMA Oncol. 2026 Jul 30. doi: 10.1001/jamaoncol.2026.2576. Online ahead of print. PubMed 42530945 ↗
  • Teng X, Ma J, Zhang J, Zhao M, Meng X, Yin Y, Xiao H, Lai Q, Zhang X, Jiang Y, Cai J. Longitudinal DCE MRI Vascular Textures: Radiologic and Biologic Insights for pCR Prediction in HER2-Negative Breast Cancer. Radiol Artif Intell. 2026 May;8(3):e250734. doi: 10.1148/ryai.250734. PubMed 41879562 ↗
  • Hensley M, Lengfeld J, Stoesz S, Edwards M, Pass F, Hirst GL, Brown-Swigart L, van 't Veer L, Esserman LJ, Beckwith H, Yee D. Detection of serum HER2 in patients treated with neratinib or trastuzumab: analysis of the I-SPY Trial. Front Oncol. 2025 Jul 24;15:1605120. doi: 10.3389/fonc.2025.1605120. eCollection 2025. PubMed 40777112 ↗
  • Gilad M, Partridge SC, Iima M, Md RR, Freiman M. Radiomics-based Machine Learning Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Using Physiologically Decomposed Diffusion-weighted MRI. Radiol Imaging Cancer. 2025 Jul;7(4):e240312. doi: 10.1148/rycan.240312. PubMed 40679371 ↗
  • Jing B, Wang J. A two-stage dual-task learning strategy for early prediction of pathological complete response to neoadjuvant chemotherapy for breast cancer using dynamic contrast-enhanced magnetic resonance images. Phys Med Biol. 2025 Jul 18;70(14):145030. doi: 10.1088/1361-6560/adee73. PubMed 40639409 ↗
  • Leon-Ferre RA, Dimitroff K, Yau C, Giridhar KV, Mukhtar R, Hirst G, Hylton N, Perlmutter J, DeMichele A, Yee D, van 't Veer L, Rugo H, Symmans WF, Goetz MP, Esserman L, Boughey JC. Combined prognostic impact of initial clinical stage and residual cancer burden after neoadjuvant systemic therapy in triple-negative and HER2-positive breast cancer: an analysis of the I-SPY2 randomized clinical trial. Breast Cancer Res. 2025 Jun 23;27(1):115. doi: 10.1186/s13058-025-02070-1. PubMed 40551254 ↗
  • Wolf DM, Yau C, Campbell M, Glas A, Barcaru A, Mittempergher L, Kuilman M, Brown-Swigart L, Hirst G, Basu A, Magbanua M, Sayaman R, Huppert L, Delson A; I-SPY2 Investigators; Symmans WF, Borowsky A, Pohlmann P, Rugo H, Clark A, Yee D, DeMichele A, Perlmutter J, Petricoin EF, Chien J, Stringer-Reasor E, Shatsky R, Liu M, Han H, Soliman H, Isaacs C, Nanda R, Hylton N, Pusztai L, Esserman L, van 't Veer L. Immune Subtyping Identifies Patients With Hormone Receptor-Positive Early-Stage Breast Cancer Who Respond to Neoadjuvant Immunotherapy (IO): Results From Five IO Arms of the I-SPY2 Trial. JCO Precis Oncol. 2025 Jun;9:e2400776. doi: 10.1200/PO-24-00776. Epub 2025 Jun 17. PubMed 40526879 ↗
  • Rugo HS, Campbell M, Yau C, Jo Chien A, Wallace AM, Isaacs C, Boughey JC, Han HS, Buxton M, Clennell JL, Asare SM, Steeg K, Wilson A, Singhrao R, Matthews JB, Perlmutter J, Fraser Symmans W, Hylton NM, DeMichele AM, Yee D, Van't Veer LJ, Berry DA, Esserman LJ. Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer. Breast Cancer Res Treat. 2025 Feb;209(3):487-492. doi: 10.1007/s10549-024-07555-9. Epub 2024 Dec 3. PubMed 39625569 ↗
  • Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothe F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nat Commun. 2024 Nov 29;15(1):10402. doi: 10.1038/s41467-024-54621-3. PubMed 39613746 ↗
  • Shatsky RA, Trivedi MS, Yau C, Nanda R, Rugo HS, Davidian M, Tsiatis B, Wallace AM, Chien AJ, Stringer-Reasor E, Boughey JC, Omene C, Rozenblit M, Kalinsky K, Elias AD, Vaklavas C, Beckwith H, Williams N, Arora M, Nangia C, Roussos Torres ET, Thomas B, Albain KS, Clark AS, Falkson C, Hershman DL, Isaacs C, Thomas A, Tseng J, Sanford A, Yeung K, Boles S, Chen YY, Huppert L, Jahan N, Parker C, Giridhar K, Howard FM, Blackwood MM, Sanft T, Li W, Onishi N, Asare AL, Beineke P, Norwood P, Brown-Swigart L, Hirst GL, Matthews JB, Moore B, Symmans WF, Price E, Heditsian D, LeStage B, Perlmutter J, Pohlmann P, DeMichele A, Yee D, van 't Veer LJ, Hylton NM, Esserman LJ. Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. Nat Med. 2024 Dec;30(12):3737-3747. doi: 10.1038/s41591-024-03267-1. Epub 2024 Sep 14. PubMed 39277672 ↗
  • Khoury K, Meisel JL, Yau C, Rugo HS, Nanda R, Davidian M, Tsiatis B, Chien AJ, Wallace AM, Arora M, Rozenblit M, Hershman DL, Zimmer A, Clark AS, Beckwith H, Elias AD, Stringer-Reasor E, Boughey JC, Nangia C, Vaklavas C, Omene C, Albain KS, Kalinsky KM, Isaacs C, Tseng J, Roussos Torres ET, Thomas B, Thomas A, Sanford A, Balassanian R, Ewing C, Yeung K, Sauder C, Sanft T, Pusztai L, Trivedi MS, Outhaythip A, Li W, Onishi N, Asare AL, Beineke P, Norwood P, Brown-Swigart L, Hirst GL, Matthews JB, Moore B, Fraser Symmans W, Price E, Beedle C, Perlmutter J, Pohlmann P, Shatsky RA, DeMichele A, Yee D, van 't Veer LJ, Hylton NM, Esserman LJ. Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. Nat Med. 2024 Dec;30(12):3728-3736. doi: 10.1038/s41591-024-03266-2. Epub 2024 Sep 14. PubMed 39277671 ↗
  • Northrop A, Christofferson A, Umashankar S, Melisko M, Castillo P, Brown T, Heditsian D, Brain S, Simmons C, Hieken T, Ruddy KJ, Mainor C, Afghahi A, Tevis S, Blaes A, Kang I, Asare A, Esserman L, Hershman DL, Basu A. Implementation and impact of an electronic patient reported outcomes system in a phase II multi-site adaptive platform clinical trial for early-stage breast cancer. J Am Med Inform Assoc. 2025 Jan 1;32(1):172-180. doi: 10.1093/jamia/ocae190. PubMed 39158353 ↗
  • Xu J, Gao H, Guan X, Meng J, Ding S, Long Q, Yi W. Circulating tumor DNA: from discovery to clinical application in breast cancer. Front Immunol. 2024 Apr 30;15:1355887. doi: 10.3389/fimmu.2024.1355887. eCollection 2024. PubMed 38745646 ↗
  • Li W, Partridge SC, Newitt DC, Steingrimsson J, Marques HS, Bolan PJ, Hirano M, Bearce BA, Kalpathy-Cramer J, Boss MA, Teng X, Zhang J, Cai J, Kontos D, Cohen EA, Mankowski WC, Liu M, Ha R, Pellicer-Valero OJ, Maier-Hein K, Rabinovici-Cohen S, Tlusty T, Ozery-Flato M, Parekh VS, Jacobs MA, Yan R, Sung K, Kazerouni AS, DiCarlo JC, Yankeelov TE, Chenevert TL, Hylton NM. Breast Multiparametric MRI for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: The BMMR2 Challenge. Radiol Imaging Cancer. 2024 Jan;6(1):e230033. doi: 10.1148/rycan.230033. PubMed 38180338 ↗
  • Gallagher RI, Wulfkuhle J, Wolf DM, Brown-Swigart L, Yau C, O'Grady N, Basu A, Lu R, Campbell MJ, Magbanua MJ, Coppe JP; I-SPY 2 Investigators; Asare SM, Sit L, Matthews JB, Perlmutter J, Hylton N, Liu MC, Symmans WF, Rugo HS, Isaacs C, DeMichele AM, Yee D, Pohlmann PR, Hirst GL, Esserman LJ, van 't Veer LJ, Petricoin EF. Protein signaling and drug target activation signatures to guide therapy prioritization: Therapeutic resistance and sensitivity in the I-SPY 2 Trial. Cell Rep Med. 2023 Dec 19;4(12):101312. doi: 10.1016/j.xcrm.2023.101312. Epub 2023 Dec 11. PubMed 38086377 ↗
  • Onishi N, Bareng TJ, Gibbs J, Li W, Price ER, Joe BN, Kornak J, Esserman LJ, Newitt DC, Hylton NM; I-SPY 2 Imaging Working Group; I-SPY 2 Investigator Network. Effect of Longitudinal Variation in Tumor Volume Estimation for MRI-guided Personalization of Breast Cancer Neoadjuvant Treatment. Radiol Imaging Cancer. 2023 Jul;5(4):e220126. doi: 10.1148/rycan.220126. PubMed 37505107 ↗
  • Mukhtar RA, Chau H, Woriax H, Piltin M, Ahrendt G, Tchou J, Yu H, Ding Q, Dugan CL, Sheade J, Crown A, Carr M, Wong J, Son J, Yang R, Chan T, Terando A, Alvarado M, Ewing C, Tonneson J, Tamirisa N, Gould R, Singh P, Godellas C, Larson K, Chiba A, Rao R, Sauder C, Postlewait L, Lee MC, Symmans WF, Esserman LJ, Boughey JC; ISPY-2 Locoregional Working Group. Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial. Ann Surg. 2023 Sep 1;278(3):320-327. doi: 10.1097/SLA.0000000000005968. Epub 2023 Jun 16. PubMed 37325931 ↗
  • Parker BA, Shatsky RA, Schwab RB, Wallace AM; I-SPY 2 Consortium; Wolf DM, Hirst GL, Brown-Swigart L, Esserman LJ, van 't Veer LJ, Ghia EM, Yau C, Kipps TJ. Association of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial. Breast Cancer Res Treat. 2023 Jun;199(2):281-291. doi: 10.1007/s10549-023-06914-2. Epub 2023 Apr 8. PubMed 37029329 ↗
  • Lang JE, Forero-Torres A, Yee D, Yau C, Wolf D, Park J, Parker BA, Chien AJ, Wallace AM, Murthy R, Albain KS, Ellis ED, Beckwith H, Haley BB, Elias AD, Boughey JC, Yung RL, Isaacs C, Clark AS, Han HS, Nanda R, Khan QJ, Edmiston KK, Stringer-Reasor E, Price E, Joe B, Liu MC, Brown-Swigart L, Petricoin EF, Wulfkuhle JD, Buxton M, Clennell JL, Sanil A, Berry S, Asare SM, Wilson A, Hirst GL, Singhrao R, Asare AL, Matthews JB, Melisko M, Perlmutter J, Rugo HS, Symmans WF, van 't Veer LJ, Hylton NM, DeMichele AM, Berry DA, Esserman LJ. Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer. NPJ Breast Cancer. 2022 Dec 1;8(1):128. doi: 10.1038/s41523-022-00493-z. PubMed 36456573 ↗
  • Osdoit M, Yau C, Symmans WF, Boughey JC, Ewing CA, Balassanian R, Chen YY, Krings G, Wallace AM, Zare S, Fadare O, Lancaster R, Wei S, Godellas CV, Tang P, Tuttle TM, Klein M, Sahoo S, Hieken TJ, Carter JM, Chen B, Ahrendt G, Tchou J, Feldman M, Tousimis E, Zeck J, Jaskowiak N, Sattar H, Naik AM, Lee MC, Rosa M, Khazai L, Rendi MH, Lang JE, Lu J, Tawfik O, Asare SM, Esserman LJ, Mukhtar RA. Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial. JAMA Surg. 2022 Nov 1;157(11):1034-1041. doi: 10.1001/jamasurg.2022.4118. PubMed 36069821 ↗
  • Trapani D, Ferraro E, Giugliano F, Boscolo Bielo L, Curigliano G, Burstein HJ. Postneoadjuvant treatment for triple-negative breast cancer. Curr Opin Oncol. 2022 Nov 1;34(6):623-634. doi: 10.1097/CCO.0000000000000893. Epub 2022 Aug 19. PubMed 35993306 ↗
  • Wolf DM, Yau C, Wulfkuhle J, Brown-Swigart L, Gallagher RI, Lee PRE, Zhu Z, Magbanua MJ, Sayaman R, O'Grady N, Basu A, Delson A, Coppe JP, Lu R, Braun J; I-SPY2 Investigators; Asare SM, Sit L, Matthews JB, Perlmutter J, Hylton N, Liu MC, Pohlmann P, Symmans WF, Rugo HS, Isaacs C, DeMichele AM, Yee D, Berry DA, Pusztai L, Petricoin EF, Hirst GL, Esserman LJ, van 't Veer LJ. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022 Jun 13;40(6):609-623.e6. doi: 10.1016/j.ccell.2022.05.005. Epub 2022 May 26. PubMed 35623341 ↗
  • Engebraaten O, Yau C, Berg K, Borgen E, Garred O, Berstad MEB, Fremstedal ASV, DeMichele A, Veer LV', Esserman L, Weyergang A. RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer. Nat Commun. 2021 Nov 5;12(1):6427. doi: 10.1038/s41467-021-26018-z. PubMed 34741021 ↗
  • Symmans WF, Yau C, Chen YY, Balassanian R, Klein ME, Pusztai L, Nanda R, Parker BA, Datnow B, Krings G, Wei S, Feldman MD, Duan X, Chen B, Sattar H, Khazai L, Zeck JC, Sams S, Mhawech-Fauceglia P, Rendi M, Sahoo S, Ocal IT, Fan F, LeBeau LG, Vinh T, Troxell ML, Chien AJ, Wallace AM, Forero-Torres A, Ellis E, Albain KS, Murthy RK, Boughey JC, Liu MC, Haley BB, Elias AD, Clark AS, Kemmer K, Isaacs C, Lang JE, Han HS, Edmiston K, Viscusi RK, Northfelt DW, Khan QJ, Leyland-Jones B, Venters SJ, Shad S, Matthews JB, Asare SM, Buxton M, Asare AL, Rugo HS, Schwab RB, Helsten T, Hylton NM, van 't Veer L, Perlmutter J, DeMichele AM, Yee D, Berry DA, Esserman LJ. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial. JAMA Oncol. 2021 Nov 1;7(11):1654-1663. doi: 10.1001/jamaoncol.2021.3690. PubMed 34529000 ↗
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09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Mar 2010 (actual). Primary completion is estimated for Dec 2030, 249 months after the start.

Of 220 non-industry phase 2 interventional studies under Triple Negative Breast Neoplasms, half reached primary completion within 60 months of starting (the median), counting those still running; a quarter within 38 and three quarters within 99. This study's planned 249 months is above that.

Counting every sponsor, half of 255 studies reached it within 59 months; a quarter within 37 and three quarters within 94.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 31, 2009
First posted
Jan 5, 2010
StartActual
Mar 1, 2010
Primary completionEst.
Dec 2030
CompletionEst.
Dec 2031
Last update
May 6, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 6, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01042379
Lead sponsor
QuantumLeap Healthcare Collaborative
Responsible party
Sponsor
First posted
Jan 5, 2010
Start date
Mar 1, 2010
Primary completion
Dec 2030 (estimated)
Completion
Dec 2031 (estimated)
Last update
May 6, 2026

Study contacts

Won Chang
Contact
w.chang@quantumleaphealth.org
(855) 866-0505
Heather Prisant
Contact
h.prisant@qlhc.org
Laura Esserman, MD, MBA
principal investigator · University of California, San Francisco

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Ganitumab · Ado-Trastuzumab Emtansine · Pertuzumab · STA 9090 · Veliparib · Neratinib · Pexidartinib · Pembrolizumab · Talazoparib · Irinotecan · SGN-LIV1A · Durvalumab · Olaparib · Nelitolimod · Tucatinib · Trastuzumab · Cemiplimab · Fianlimab · Trastuzumab duocarmazine · Amcenestrant · Abemaciclib · Letrozole · ARX788 · Datopotamab deruxtecan · Zanidatamab · Lasofoxifene · Endoxifen · Vepdegestrant · Rilvegostomig · Niraparib · Sarilumab · Paclitaxel · Mocertatug rezetecan · Dostarlimab · Ivonescimab

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