AzTrials
AzTrials

Breast NeoplasmsPhase 2I-SPYNCT01042379

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

A Phase 2 study testing Standard Therapy, AMG 386 with or without Trastuzumab and AMG 479 (Ganitumab) plus Metformin in people with Breast Neoplasms and Breast Cancer, run by QuantumLeap Healthcare Collaborative at 42 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Neoplasms, Breast Cancer, Breast Tumors
What is being tested?
Standard Therapy, AMG 386 with or without Trastuzumab and AMG 479 (Ganitumab) plus Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5,000 participants
Where
42 sitesUnited States
Study dates
1 Mar 2010to Dec 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed invasive cancer of the breast
  • Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)
  • No prior cytotoxic regimens are allowed for this malignancy. 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
  • ECOG performance status 0-1
  • Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
Show all 16Show fewer
  • 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 informed consent (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 metastasis
  • Any tumor ER/PgR status, any HER-2/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, Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN, AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN
  • No uncontrolled or severe cardiac disease. Baseline ejection fraction (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)

Who cannot join

  • Use of any other investigational 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

Trial locations and contacts

42 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Won Chang contact

(855) 866-0505

w.chang@quantumleaphealth.org

Heather Prisant contact

h.prisant@qlhc.org

42 sites in 1 country

United States42 sites, 33 recruiting

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

    Kevin Kalinsky, MD

    Recruiting

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

    720-848-1622

    Anthony Elias, MD

    Recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Erica Stringer-Reasor, MD

    Recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

    Ellis Levine, MD

    Recruiting

  • University of Chicago

    Chicago, Illinois, 60453

    773-834-2756

    Rita Nanda, MD

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44106

    800-233-2273

    Julie Lang, MD

    Recruiting

  • The Ohio State University, Stefanie Spielman Comprehensive Breast Center

    Columbus, Ohio, 43212

    Nicole Williams, MD

    Recruiting

  • University of Texas, Southwestern Medical Center

    Dallas, Texas, 75390-9155

    Active, not recruiting

  • University of California - Davis, Comprehensive Cancer Center

    Davis, California, 95817

    Mili Arora, MD

    Recruiting

  • City of Hope

    Duarte, California, 91010

    800-826-4673

    Hope Rugo, MD

    Recruiting

  • Inova Health System

    Falls Church, Virginia, 22042

    Active, not recruiting

  • University of Texas, M.D. Anderson Cancer Center

    Houston, Texas, 77230-1439

    Active, not recruiting

  • University of California San Diego

    La Jolla, California, 92093-0698

    858-822-6194

    858-822-6194, CancerCTO@ucsd.edu

    Recruiting

  • Herbert-Herman Cancer Center, Sparrow Hospital

    Lansing, Michigan, 48912

    Brittani Thomas, DO

    Recruiting

  • University of Southern California

    Los Angeles, California, 90033

    Kristy Watkins, RN, 323-865-0452, Watkins_K@ccnt.usc.edu

    Evanthia Roussos Torres, MD

    Recruiting

  • Loyola University

    Maywood, Illinois, 60153

    708-327-3102

    Kathy S Albain, MD

    Recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    612-626-8487

    Douglas Yee, MD

    Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 27204

    Active, not recruiting

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

    732-235-7356

    Coral Omene, MD, PhD

    Recruiting

  • Yale Cancer Center

    New Haven, Connecticut, 06510

    Trisha Burello, MS, 203-737-2848, trisha.burrello@yale.edu

    Tara Snaft, MD

    Recruiting

  • Laura and Isaac Perlmutter Cancer Center / NYU Langone Health

    New York, New York, 10016

    Yannis Karamitas, Yannis.Karamitas@nyulangone.org

    Nancy Chan, MD

    Recruiting

  • Columbia University Medical Center

    New York, New York, 10032

    Meghana Trivedi, MD

    Recruiting

  • HOAG Memorial Hospital Presbyterian

    Newport Beach, California, 92663

    Chaitali Nangia, MD

    Recruiting

  • University of Pennsylvania (U Penn)

    Philadelphia, Pennsylvania, 19104

    215-614-1850

    Amy Clark, MD

    Recruiting

  • University Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

    Active, not recruiting

  • Oregon Health & Science Institute (OHSU)

    Portland, Oregon, 97239

    Brienna Palm, 503-494-4438, palmb@ohsu.edu

    503-494-8573

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    507-538-7623

    Judy C Boughey, MD

    Recruiting

  • University of Rochester Wilmot Cancer Institute

    Rochester, New York, 14642

    WCICTOResearch@urmc.rochester.edu

    Carla Folksm, MD

    Recruiting

  • Metro Minnesota Community Oncology Research Consortium, Hennepin County Medical Center

    Saint Louis Park, Minnesota, 55416

    Satya Bommakanti, MD

    Recruiting

  • Huntsman Cancer Institute, University of Utah

    Salt Lake City, Utah, 84112

    Christos Vaklavas, MD

    Recruiting

  • University of California San Francisco (UCSF)

    San Francisco, California, 94115

    Clinical Research Coordinator, 415-443-4296, ispycrc@ucsf.edu

    Amy Jo Chien, MD

    Recruiting

  • Mayo Clinic - Scottsdale

    Scottsdale, Arizona, 85259

    507-538-7623

    Donald Northfelt, MD

    Not yet recruiting

  • Swedish Cancer Institute

    Seattle, Washington, 98104

    Active, not recruiting

  • University of Washington

    Seattle, Washington, 98115

    Active, not recruiting

  • Sanford Clinical Research

    Sioux Falls, South Dakota, 57104

    Amy Sanford, MD

    Recruiting

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

    Hyo Heather Han, MD

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Heather Han, MD

    Recruiting

  • Montefiore Medical Center

    The Bronx, New York, 10467

    Jesus D Anampa

    Recruiting

  • University of Arizona

    Tucson, Arizona, 85724

    Active, not recruiting

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

    Minetta Liu, MD, 202-444-3677, Liumc@georgetown.edu

    Claudine Isaacs, MD

    Recruiting

  • University of Kansas

    Westwood, Kansas, 66205

    Active, not recruiting

  • Wake Forest Baptist Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

    Angela Howell, MD, 336-716-5440, anhowell@wakehealth.edu

    Marissa Howard-McNatt, MD

    Recruiting

Other trials in United States

About this study

Official title: I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

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.

Being tested
Standard Therapy, AMG 386 with or without Trastuzumab, AMG 479 (Ganitumab) plus Metformin, MK-2206 with or without Trastuzumab, AMG 386 and Trastuzumab
Keywords
Neoadjuvant, Breast, Cancer, Neoplasm, Adaptive, pCR, Pathologic Complete Response, Biomarkers signature, MRI Volume, Endocrine Therapy, Chemotherapy, Immunotherapy
Medical subject headings
Breast Neoplasms, Hemangiosarcoma, Triple Negative Breast Neoplasms, Neoplasms, Pathologic Complete Response

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard TherapyDrug

    Also called Paclitaxel (Taxol); Doxorubicin (Adriamycin)

    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

  • AMG 386 with or without TrastuzumabDrug

    Also called AMG 386 (Trebananib); (Trastuzumab) Herceptin

    Arm is closed.

  • AMG 479 (Ganitumab) plus MetforminDrug

    Also called Ganitumab

    Arm is closed.

  • MK-2206 with or without TrastuzumabDrug

    Also called (Trastuzumab) Herceptin

    Arm is closed.

  • AMG 386 and TrastuzumabDrug

    Also called AMG 386 (Trebananib); Trastuzumab (Herceptin)

    Arm is closed.

  • T-DM1 and PertuzumabDrug

    Also called T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)

    Arm is closed.

  • Pertuzumab and TrastuzumabDrug

    Also called Pertuzumab (Perjeta); Trastuzumab (Herceptin)

    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

  • GanetespibDrug

    Arm is closed.

  • ABT-888Drug

    Also called Veliparib

    Arm is closed.

  • NeratinibDrug

    Arm is closed.

  • PLX3397Drug

    Arm is closed.

  • Pembrolizumab - 4 cycleDrug

    Arm is closed.

  • Talazoparib plus IrinotecanDrug

    Arm is closed.

  • Patritumab and TrastuzumabDrug

    Arm is closed.

  • Pembrolizumab - 8 cycleDrug

    Arm is closed.

  • SGN-LIV1ADrug

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

  • Durvalumab plus OlaparibDrug

    Arm is closed.

  • SD-101 + PembrolizumabDrug

    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

  • Tucatinib plus trastuzumab and pertuzumabDrug

    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

  • CemiplimabDrug

    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

  • Cemiplimab plus REGN3767Drug

    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

  • Trilaciclib with or without trastuzumab + pertuzumabDrug

    Also called Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)

    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

  • SYD985 ([vic-]trastuzumab duocarmazine)Drug

    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

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

    Also called Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

    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

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

    Also called Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

    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

  • AmcenestrantDrug

    Also called SAR439859

    Arm is closed.

    Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks.

  • Amcenestrant + AbemaciclibDrug

    Also called Amcenestrant (SAR439859), Abemaciclib (Verzenio)

    Arm is closed.

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

  • Amcenestrant + LetrozoleDrug

    Also called Amcenestrant (SAR439859), Letrozole (Femara)

    Arm is closed.

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

  • ARX788Drug

    Arm is closed.

    ARX788, 1.5 mg/kg Q3W, IV for 12 weeks

  • ARX788 + CemiplimabDrug

    Arm is closed.

    ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks

  • VV1 + CemiplimabDrug

    Also called VOYAGER V1™, VSV-IFNβ-NIS

    Arm is closed.

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

  • Datopotamab deruxtecanDrug

    Also called Dato-DXd

    Arm is closed.

    Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks

  • Datopotamab deruxtecan + DurvalumabDrug

    Also called Dato-DXd

    Arm is closed.

    Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks

  • ZanidatamabDrug

    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.

  • LasofoxifeneDrug

    Arm is closed.

    Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks

  • Z-endoxifenDrug

    Arm is closed.

    Z-endoxifen: 10 mg QD, p.o., for 24 weeks

  • ARV-471Drug

    Arm is closed.

    ARV-471: 200 mg QD, p.o, for 24 weeks.

  • ARV-471 + LetrozoleDrug

    Arm is closed.

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

  • ARV-471 + AbemaciclibDrug

    Arm is closed.

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

  • Endoxifen + AbemaciclibDrug

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

  • Rilvegostomig + TDXdDrug

    Arm closed to accrual

    Rilvegostomig: 750mg IV Q3W for 12 weeks TDXd: 5.4 mg/kg IV Q3W for 12 weeks

  • Dan222 + NiraparibDrug

    Arm is closed.

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

  • Sarilumab + Cemiplimab + PaclitaxelDrug

    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

  • GSK 5733584Drug

    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.

  • GSK 5733584 + DostarlimabDrug

    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.

  • Ivonescimab (20mg/kg Q3W)Drug

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

    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).

Study groups in NCT01042379
Study groupRoleWhat they receive
Standard TherapyActive comparatorPaclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
Receives: Drug: Standard Therapy
AMG 386 with or without TrastuzumabExperimentalArm is closed.
Receives: Drug: AMG 386 with or without Trastuzumab; Drug: AMG 386 and Trastuzumab
AMG 479 plus MetforminOtherArm is closed.
Receives: Drug: AMG 479 (Ganitumab) plus Metformin
MK-2206 with or without TrastuzumabExperimentalArm is closed.
Receives: Drug: MK-2206 with or without Trastuzumab
T-DM1 and PertuzumabExperimentalArm is closed.
Receives: Drug: T-DM1 and Pertuzumab
Pertuzumab and TrastuzumabActive comparatorArm is closed. Novel Control Investigational Agent.
Receives: Drug: Pertuzumab and Trastuzumab
GanetespibExperimentalArm is closed.
Receives: Drug: Ganetespib
ABT-888OtherArm is closed.
Receives: Drug: ABT-888
NeratinibOtherArm is closed.
Receives: Drug: Neratinib
PLX3397ExperimentalArm is closed.
Receives: Drug: PLX3397
Pembrolizumab 4 cycleExperimentalArm is closed.
Receives: Drug: Pembrolizumab - 4 cycle
Talazoparib plus IrinotecanExperimentalArm is closed.
Receives: Drug: Talazoparib plus Irinotecan
Patritumab with or without TrastuzumabExperimentalArm is closed.
Receives: Drug: Patritumab and Trastuzumab
Pembrolizumab 8 cycleExperimentalArm is closed.
Receives: Drug: Pembrolizumab - 8 cycle
SGN-LIV1AExperimentalArm is closed.
Receives: Drug: SGN-LIV1A
Durvalumab plus OlaparibExperimentalArm is closed.
Receives: Drug: Durvalumab plus Olaparib
SD-101 + PembrolizumabExperimentalArm is closed.
Receives: Drug: SD-101 + Pembrolizumab
TucatinibExperimentalArm is closed.
Receives: Drug: Tucatinib plus trastuzumab and pertuzumab
CemiplimabExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Cemiplimab
Cemiplimab plus REGN3767ExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Cemiplimab plus REGN3767
Trilaciclib with or without trastuzumab + pertuzumabExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Trilaciclib with or without trastuzumab + pertuzumab
SYD985 ([vic-]trastuzumab duocarmazine)ExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: SYD985 ([vic-]trastuzumab duocarmazine)
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumabExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumabExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
Endocrine Optimization Pilot: Amcenestrant MonotherapyExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Amcenestrant
Endocrine Optimization Pilot: Amcenestrant + AbemaciclibExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Amcenestrant + Abemaciclib
Endocrine Optimization Pilot: Amcenestrant + LetrozoleExperimentalArm is closed. Novel Investigational Agent.
Receives: Drug: Amcenestrant + Letrozole
ARX788 in Block A and followed by SOC in Block BExperimentalArm is closed for accrual for accrual. Novel investigational Agent followed by SOC.
Receives: Drug: ARX788
ARX788 + Cemiplimab in Block A and followed by SOC in Block BExperimentalArm is closed for accrual. Novel investigational Agent followed by SOC.
Receives: Drug: ARX788 + Cemiplimab
VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block BExperimentalArm is closed for accrual. Novel investigational Agent followed by SOC.
Receives: Drug: VV1 + Cemiplimab
Datopotamab Deruxtecan in Block A and followed by SOC in block BExperimentalArm is closed for accrual. Novel investigational Agent followed by SOC.
Receives: Drug: Datopotamab deruxtecan
Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block BExperimentalArm is closed for accrual. Novel investigational Agent followed by SOC.
Receives: Drug: Datopotamab deruxtecan + Durvalumab
Zanidatamab for Block ABCExperimentalArm open for accrual. Novel investigational Agent.
Receives: Drug: Zanidatamab
Endocrine Optimization Pilot: LasofoxifeneExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: Lasofoxifene
Endocrine Optimization Pilot: (Z)-EndoxifenExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: Z-endoxifen
Endocrine Optimization Pilot: ARV-471ExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: ARV-471
Endocrine Optimization Pilot: ARV-471 + LetrozoleExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: ARV-471 + Letrozole
Endocrine Optimization Pilot: ARV-471 + AbemaciclibExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: ARV-471 + Abemaciclib
Endocrine Optimization Pilot: (Z)-Endoxifen + AbemaciclibExperimentalArm is closed for accrual. Enrollment completed. Novel investigational Agent.
Receives: Drug: Endoxifen + Abemaciclib
Rilvegostomig + TDXd in Block A and followed by SOC in Block BExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: Rilvegostomig + TDXd
DAN222 + Niraparib in Block A and followed by SOC in Block BExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: Dan222 + Niraparib
Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block CExperimentalArm is closed for accrual. Novel investigational Agent.
Receives: Drug: Sarilumab + Cemiplimab + Paclitaxel
GSK 5733584 in Block A and followed by SOC in Block BExperimentalArm is open for accrual. Novel Investigational Agent.
Receives: Drug: GSK 5733584
GSK 5733584 + Dostarlimab in Block A and followed by SOC in Block BExperimentalArm is open for accrual. Novel Investigational Agent.
Receives: Drug: GSK 5733584 + Dostarlimab
Ivonescimab in Blocks A and BExperimentalOpen for accrual. Novel Investigational Agent.
Receives: Drug: Ivonescimab (20mg/kg Q3W)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Post surgery based on upto 36-week treatment

Secondary outcomes (4)

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

    Measured: 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.

    Measured: 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.

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

  4. MRI Volume

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2010 (estimated)
  2. Study start1 Mar 2010
  3. Primary completionDec 2030 (estimated)
  4. Study completionDec 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01042379
Sponsor's protocol ID
097517
Acronym
I-SPY
Status last verified
May 2026
First submitted
31 Dec 2009
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009 Jul;86(1):97-100. doi: 10.1038/clpt.2009.68. Epub 2009 May 13.

    PubMed 19440188

  • Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA. 2011 Dec 21;306(23):2608-9. doi: 10.1001/jama.2011.1837. No abstract available.

    PubMed 22187281

  • 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

  • I-SPY2 Trial Investigators and Advocates; O'Sullivan CC, Kalinsky KM, Yau C, Kulkarni T, Yee D, Wallace AM, Chien AJ, Boughey JC, Elias AD, Nanda R, Isaacs C, Omene C, Stringer-Reasor E, Clark AS, Thomas A, Han HS, Chan N, Williams N, Trivedi MS, Arora M, Vaklavas C, Tseng J, Bommakanti S, Anampa Mesias JD, Zimmer A, Falkson C, Torres ER, Nangia C, Albain KS, Rozenblit M, Zare S, Fazelli S, Chen YY, Huppert LA, Church AL, Beckwith H, Carroll E, Solanki M, Borges VF, Tevis SEA, Chen N, Zeck JC, Kowzun MJ, Sullivan J, Marshall N, Klein ME, Giridhar KV, Acharya-Leon R, Fan B, Walsh EM, Litvak A, Jahan N, McDonald E, Douglas EH, Zena J, Guth A, Johnson K, McGuinness JE, Matsuda K, Shakeri S, Krishnamurthy J, Kang I, Madans A, Feldman S, Johnson M, Katerji H, Ma Y, Matthews JB, Delson AL, LeStage B, Perlmutter J, Petricoin EF, Shatsky RA, Price E, Basu A, Asare AL, Helsten T, McNatt MH, Mukhtar RA, Symmans WF, Borowsky AD, Heshman DL, DeMichele AM, Rugo HS, Hylton NM, van 't Veer LJ, Esserman LJ. Rilvegostomig Plus Trastuzumab-Deruxtecan for Early-Stage Breast Cancer: The I-SPY2.2 Randomized Clinical Trial. JAMA Oncol. 2026 Oct 22:e264258. doi: 10.1001/jamaoncol.2026.4258. Online ahead of print.

    PubMed 42911610

  • Nakano H, Shiinoki T. Separating Ranking Signal, Incremental Feature Value, and Evaluation-Induced Optimism in Breast MRI Treatment-Effect Analysis: Foundation Model and Radiomic Representations. J Imaging Inform Med. 2026 Sep 29. doi: 10.1007/s10278-026-02344-w. Online ahead of print.

    PubMed 42811224

  • Magbanua MJM, Wolf DM, Yau C, Manon NA, Sayaman RW, Brown Swigart L, Hirst G, Li W, Isaacs C, Shatsky R, Clark AS, Zimmer A, Mukhtar R, Delson AL, Perlmutter J, Pohlmann PR, Hylton NM, Nanda R, Yee D, Symmans WF, Esserman LJ, Rugo HS, DeMichele A, van 't Veer LJ. Circulating tumor DNA concentration at diagnosis is a modifiable prognostic factor for distant metastatic recurrence in patients with high-risk breast cancer receiving neoadjuvant therapy. medRxiv [Preprint]. 2026 Jul 29:2026.07.28.26358343. doi: 10.64898/2026.07.28.26358343.

    PubMed 42619946

  • Tseng J, Dimitroff K, Sauder CAM, Chien AJ, Ahmed KA, Allen LF, Arciero CA, Burke EE, Chandler JM, Jordan JE, Golshan M, Gutnik LA, Jaskowiak NT, Hewitt KC, Howard-McNatt M, Ito F, Kang IM, Kesmodel SB, Kuerer HM, Lee MC, Moran MC, Postlewait LM, Prionas ND, Rao R, Reyna CR, Schwer A, Taunk NK, Tchou J, Wallace AM, Li TJ, Perlmutter J, DeMichele AM, Yee D, Hylton NM, Veer LJV, Rugo HS, Symmans WF, Shatsky RA, Isaacs CJD, Yau C, Esserman LJ, Boughey JC, Mukhtar RA. Surgical Management of Young Women with High-Risk Breast Cancer Receiving Neoadjuvant Systemic Therapy on the I-SPY2 Trial. Ann Surg Oncol. 2026 Aug 3. doi: 10.1245/s10434-026-20153-x. Online ahead of print.

    PubMed 42545411

  • 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:e262576. 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard Therapy, AMG 386 with or without Trastuzumab and AMG 479 (Ganitumab) plus Metformin in people with Breast Neoplasms and Breast Cancer, run by QuantumLeap Healthcare Collaborative at 42 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Won Chang ((855) 866-0505, w.chang@quantumleaphealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01042379, which also lists 41 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.

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