Skip to main content
OpenTrials
Recruiting

NCT Number: NCT01042379

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Breast Neoplasms Angiosarcoma Breast Cancer Breast Diseases Breast Tumors Disease Attributes Disease Progression Early-Stage Breast Cancer HER2-negative Breast Cancer HER2-positive Breast Cancer Hemangiosarcoma Hormone Receptor Negative Tumor Hormone Receptor Positive Tumor Locally Advanced Breast Cancer Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective and Soft Tissue Neoplasms, Vascular Tissue Pathologic Complete Response Pathologic Processes Pathological Conditions, Signs and Symptoms Sarcoma Skin Diseases Skin and Connective Tissue Diseases TNBC - Triple-Negative Breast Cancer Triple Negative Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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)

Exclusion criteria

  • 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

Treatment and study plan

Standard therapy

Drug

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

Other names: Paclitaxel (Taxol); Doxorubicin (Adriamycin)

AMG 386 with or without Trastuzumab

Drug

Arm is closed.

Other names: AMG 386 (Trebananib); (Trastuzumab) Herceptin

AMG 479 (Ganitumab) plus Metformin

Drug

Arm is closed.

Other names: Ganitumab

MK-2206 with or without Trastuzumab

Drug

Arm is closed.

Other names: (Trastuzumab) Herceptin

AMG 386 and Trastuzumab

Drug

Arm is closed.

Other names: AMG 386 (Trebananib); Trastuzumab (Herceptin)

T-DM1 and Pertuzumab

Drug

Arm is closed.

Other names: T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)

Pertuzumab and Trastuzumab

Drug

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

Other names: Pertuzumab (Perjeta); Trastuzumab (Herceptin)

Ganetespib

Drug

Arm is closed.

ABT-888

Drug

Arm is closed.

Other names: Veliparib

Neratinib

Drug

Arm is closed.

PLX3397

Drug

Arm is closed.

Pembrolizumab - 4 cycle

Drug

Arm is closed.

Talazoparib plus Irinotecan

Drug

Arm is closed.

Patritumab and Trastuzumab

Drug

Arm is closed.

Pembrolizumab - 8 cycle

Drug

Arm is closed.

SGN-LIV1A

Drug

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

Durvalumab plus Olaparib

Drug

Arm is closed.

SD-101 + Pembrolizumab

Drug

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 pertuzumab

Drug

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

Drug

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 REGN3767

Drug

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 + pertuzumab

Drug

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

Other names: Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)

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 trastuzumab

Drug

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

Other names: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

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

Drug

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

Other names: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)

amcenestrant

Drug

Arm is closed.

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

Other names: SAR439859

Amcenestrant + Abemaciclib

Drug

Arm is closed.

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

Other names: Amcenestrant (SAR439859), Abemaciclib (Verzenio)

Amcenestrant + Letrozole

Drug

Arm is closed.

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

Other names: Amcenestrant (SAR439859), Letrozole (Femara)

ARX788

Drug

Arm is closed.

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

ARX788 + Cemiplimab

Drug

Arm is closed.

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

VV1 + Cemiplimab

Drug

Arm is closed.

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

Other names: VOYAGER V1™, VSV-IFNβ-NIS

Datopotamab deruxtecan

Drug

Arm is closed.

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

Other names: Dato-DXd

Datopotamab deruxtecan + Durvalumab

Drug

Arm is closed.

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

Other names: Dato-DXd

Zanidatamab

Drug

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.

Lasofoxifene

Drug

Arm is closed.

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

Z-Endoxifen

Drug

Arm is closed.

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

ARV-471

Drug

Arm is closed.

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

ARV-471 + Letrozole

Drug

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 + Abemaciclib

Drug

Arm is closed.

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

Endoxifen + Abemaciclib

Drug

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

Rilvegostomig + TDXd

Drug

Arm closed to accrual

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

Dan222 + Niraparib

Drug

Arm is closed.

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

Sarilumab + Cemiplimab + Paclitaxel

Drug

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 5733584

Drug

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 + Dostarlimab

Drug

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

Strengths to be used in trial:

  • 20 mg/kg IV Q3W monotherapy
  • 20 mg/kg IV Q3W with paclitaxel
  • 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).

Other names: AK112, SMT112, PD-1 / VEGF bispecific antibody, 依达方® (Yiwoxi Dankang Zhusheye)

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

Study contacts

Contact information is provided by the study sponsor or research team.

Heather Prisant

CONTACT

[email protected]

Won Chang

CONTACT

[email protected]

(855) 866-0505

Sponsors and collaborators

Lead sponsor

QuantumLeap Healthcare Collaborative

Other

Registry information

Official study title

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

Acronym: I-SPY

Important dates

Study start
2010
Primary completion
2030
Study completion
2031
First posted
Jan 5, 2010
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.