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

NCT01042379 | Recruiting Phase 2 DMC

• 1 other identifier: 097517
• Study Type: interventional
• Target: 5,000
• Locations: 1 country
• Sites: 42

Brief 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.

Conditions

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

Outcome Measures

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.

  Post surgery based on upto 36-week treatment

Secondary Outcomes (4)

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

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

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

  Three- and Five-Year Post-surgery Follow-up

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

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

• MRI Volume

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

Study Arms (45)

Standard Therapy

ACTIVE COMPARATOR

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

Drug: Standard Therapy

AMG 386 with or without Trastuzumab

EXPERIMENTAL

Arm is closed.

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

AMG 479 plus Metformin

OTHER

Arm is closed.

Drug: AMG 479 (Ganitumab) plus Metformin

MK-2206 with or without Trastuzumab

EXPERIMENTAL

Arm is closed.

Drug: MK-2206 with or without Trastuzumab

T-DM1 and Pertuzumab

EXPERIMENTAL

Arm is closed.

Drug: T-DM1 and Pertuzumab

Pertuzumab and Trastuzumab

ACTIVE COMPARATOR

Arm is closed. Novel Control Investigational Agent.

Drug: Pertuzumab and Trastuzumab

Ganetespib

EXPERIMENTAL

Arm is closed.

Drug: Ganetespib

ABT-888

OTHER

Arm is closed.

Drug: ABT-888

Neratinib

OTHER

Arm is closed.

Drug: Neratinib

PLX3397

EXPERIMENTAL

Arm is closed.

Drug: PLX3397

Pembrolizumab 4 cycle

EXPERIMENTAL

Arm is closed.

Drug: Pembrolizumab - 4 cycle

Talazoparib plus Irinotecan

EXPERIMENTAL

Arm is closed.

Drug: Talazoparib plus Irinotecan

Patritumab with or without Trastuzumab

EXPERIMENTAL

Arm is closed.

Drug: Patritumab and Trastuzumab

Pembrolizumab 8 cycle

EXPERIMENTAL

Arm is closed.

Drug: Pembrolizumab - 8 cycle

SGN-LIV1A

EXPERIMENTAL

Arm is closed.

Drug: SGN-LIV1A

Durvalumab plus Olaparib

EXPERIMENTAL

Arm is closed.

Drug: Durvalumab plus Olaparib

SD-101 + Pembrolizumab

EXPERIMENTAL

Arm is closed.

Drug: SD-101 + Pembrolizumab

Tucatinib

EXPERIMENTAL

Arm is closed.

Drug: Tucatinib plus trastuzumab and pertuzumab

Cemiplimab

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Cemiplimab

Cemiplimab plus REGN3767

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Cemiplimab plus REGN3767

Trilaciclib with or without trastuzumab + pertuzumab

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Trilaciclib with or without trastuzumab + pertuzumab

SYD985 ([vic-]trastuzumab duocarmazine)

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: SYD985 ([vic-]trastuzumab duocarmazine)

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

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

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

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

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

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

Endocrine Optimization Pilot: Amcenestrant Monotherapy

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Amcenestrant

Endocrine Optimization Pilot: Amcenestrant + Abemaciclib

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Amcenestrant + Abemaciclib

Endocrine Optimization Pilot: Amcenestrant + Letrozole

EXPERIMENTAL

Arm is closed. Novel Investigational Agent.

Drug: Amcenestrant + Letrozole

ARX788 in Block A and followed by SOC in Block B

EXPERIMENTAL

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

Drug: ARX788

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

EXPERIMENTAL

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

Drug: ARX788 + Cemiplimab

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

EXPERIMENTAL

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

Drug: VV1 + Cemiplimab

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

EXPERIMENTAL

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

Drug: Datopotamab deruxtecan

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

EXPERIMENTAL

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

Drug: Datopotamab deruxtecan + Durvalumab

Zanidatamab for Block ABC

EXPERIMENTAL

Arm open for accrual. Novel investigational Agent.

Drug: Zanidatamab

Endocrine Optimization Pilot: Lasofoxifene

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: Lasofoxifene

Endocrine Optimization Pilot: (Z)-Endoxifen

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: Z-endoxifen

Endocrine Optimization Pilot: ARV-471

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: ARV-471

Endocrine Optimization Pilot: ARV-471 + Letrozole

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: ARV-471 + Letrozole

Endocrine Optimization Pilot: ARV-471 + Abemaciclib

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: ARV-471 + Abemaciclib

Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib

EXPERIMENTAL

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

Drug: Endoxifen + Abemaciclib

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

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: Rilvegostomig + TDXd

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

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: Dan222 + Niraparib

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

EXPERIMENTAL

Arm is closed for accrual. Novel investigational Agent.

Drug: Sarilumab + Cemiplimab + Paclitaxel

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

EXPERIMENTAL

Arm is open for accrual. Novel Investigational Agent.

Drug: GSK 5733584

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

EXPERIMENTAL

Arm is open for accrual. Novel Investigational Agent.

Drug: GSK 5733584 + Dostarlimab

Ivonescimab in Blocks A and B

EXPERIMENTAL

Open for accrual. Novel Investigational Agent.

Drug: Ivonescimab (20mg/kg Q3W)

Interventions

Pembrolizumab - 4 cycle DRUG

Arm is closed.

Pembrolizumab 4 cycle

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

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

Trilaciclib with or without trastuzumab + pertuzumab

Ivonescimab (20mg/kg Q3W) DRUG

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)

Ivonescimab in Blocks A and B

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

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

Standard Therapy

AMG 386 with or without Trastuzumab DRUG

Arm is closed.

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

AMG 386 with or without Trastuzumab

AMG 479 (Ganitumab) plus Metformin DRUG

Arm is closed.

Also known as: Ganitumab

AMG 479 plus Metformin

MK-2206 with or without Trastuzumab DRUG

Arm is closed.

Also known as: (Trastuzumab) Herceptin

MK-2206 with or without Trastuzumab

AMG 386 and Trastuzumab DRUG

Arm is closed.

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

AMG 386 with or without Trastuzumab

T-DM1 and Pertuzumab DRUG

Arm is closed.

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

T-DM1 and Pertuzumab

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

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

Pertuzumab and Trastuzumab

Ganetespib DRUG

Arm is closed.

Ganetespib

ABT-888 DRUG

Arm is closed.

Also known as: Veliparib

ABT-888

Neratinib DRUG

Arm is closed.

Neratinib

PLX3397 DRUG

Arm is closed.

PLX3397

Talazoparib plus Irinotecan DRUG

Arm is closed.

Talazoparib plus Irinotecan

Patritumab and Trastuzumab DRUG

Arm is closed.

Patritumab with or without Trastuzumab

Pembrolizumab - 8 cycle DRUG

Arm is closed.

Pembrolizumab 8 cycle

SGN-LIV1A DRUG

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

SGN-LIV1A

Durvalumab plus Olaparib DRUG

Arm is closed.

Durvalumab plus Olaparib

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

SD-101 + Pembrolizumab

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

Tucatinib

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

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

Cemiplimab plus REGN3767

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

SYD985 ([vic-]trastuzumab duocarmazine)

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

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

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

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

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

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

Amcenestrant DRUG

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

Also known as: SAR439859

Endocrine Optimization Pilot: Amcenestrant Monotherapy

Amcenestrant + Abemaciclib DRUG

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)

Endocrine Optimization Pilot: Amcenestrant + Abemaciclib

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

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

Endocrine Optimization Pilot: Amcenestrant + Letrozole

ARX788 DRUG

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

ARX788 in Block A and followed by SOC in Block B

ARX788 + Cemiplimab DRUG

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

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

VV1 + Cemiplimab DRUG

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

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

Datopotamab deruxtecan DRUG

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

Also known as: Dato-DXd

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

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

Also known as: Dato-DXd

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

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.

Zanidatamab for Block ABC

Lasofoxifene DRUG

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

Endocrine Optimization Pilot: Lasofoxifene

Z-endoxifen DRUG

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

Endocrine Optimization Pilot: (Z)-Endoxifen

ARV-471 DRUG

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

Endocrine Optimization Pilot: ARV-471

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

Endocrine Optimization Pilot: ARV-471 + Letrozole

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

Endocrine Optimization Pilot: ARV-471 + Abemaciclib

Endoxifen + Abemaciclib DRUG

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

Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib

Rilvegostomig + TDXd DRUG

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

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

Dan222 + Niraparib DRUG

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

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

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

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

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 in Block A and followed by SOC in Block B

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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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™)

You may not qualify if:

• 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

Sponsors & Collaborators

• QuantumLeap Healthcare Collaborative: lead

Study Sites (42)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

NOT YET RECRUITING

University of Arizona

Tucson, Arizona, 85724, United States

ACTIVE NOT RECRUITING

University of California - Davis, Comprehensive Cancer Center

Davis, California, 95817, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of California San Diego

La Jolla, California, 92093-0698, United States

RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

HOAG Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

University of California San Francisco (UCSF)

San Francisco, California, 94115, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60453, United States

RECRUITING

Loyola University

Maywood, Illinois, 60153, United States

RECRUITING

University of Kansas

Westwood, Kansas, 66205, United States

ACTIVE NOT RECRUITING

Herbert-Herman Cancer Center, Sparrow Hospital

Lansing, Michigan, 48912, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Metro Minnesota Community Oncology Research Consortium, Hennepin County Medical Center

Saint Louis Park, Minnesota, 55416, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

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

University of Rochester Wilmot Cancer Institute

Rochester, New York, 14642, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44106, United States

RECRUITING

The Ohio State University, Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

RECRUITING

Oregon Health & Science Institute (OHSU)

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania (U Penn)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

ACTIVE NOT RECRUITING

Sanford Clinical Research

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 27204, United States

ACTIVE NOT RECRUITING

University of Texas, Southwestern Medical Center

Dallas, Texas, 75390-9155, United States

ACTIVE NOT RECRUITING

University of Texas, M.D. Anderson Cancer Center

Houston, Texas, 77230-1439, United States

ACTIVE NOT RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Inova Health System

Falls Church, Virginia, 22042, United States

ACTIVE NOT RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

ACTIVE NOT RECRUITING

University of Washington

Seattle, Washington, 98115, United States

ACTIVE NOT RECRUITING

Related Publications (35)

• 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.

  PMID: 19440188 BACKGROUND

• 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.

  PMID: 22187281 BACKGROUND

• 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.

  PMID: 22649152 RESULT

• 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.

  PMID: 22623692 RESULT

• 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.

  PMID: 21796368 RESULT

• 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.

  PMID: 22198468 RESULT

• 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 Mar 25:e250734. doi: 10.1148/ryai.250734. Online ahead of print.

  PMID: 41879562 DERIVED

• 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.

  PMID: 40777112 DERIVED

• 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.

  PMID: 40679371 DERIVED

• 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.

  PMID: 40639409 DERIVED

• 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.

  PMID: 40551254 DERIVED

• 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.

  PMID: 40526879 DERIVED

• 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.

  PMID: 39625569 DERIVED

• 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.

  PMID: 39613746 DERIVED

• 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.

  PMID: 39277672 DERIVED

• 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.

  PMID: 39277671 DERIVED

• 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.

  PMID: 39158353 DERIVED

• 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.

  PMID: 38180338 DERIVED

• 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.

  PMID: 38086377 DERIVED

• 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.

  PMID: 37505107 DERIVED

• 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.

  PMID: 37325931 DERIVED

• 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.

  PMID: 37029329 DERIVED

• 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.

  PMID: 36456573 DERIVED

• 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.

  PMID: 36069821 DERIVED

• 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.

  PMID: 35993306 DERIVED

• 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.

  PMID: 35623341 DERIVED

• 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.

  PMID: 34741021 DERIVED

• 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.

  PMID: 34529000 DERIVED

• I-SPY2 Trial Consortium; Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, Chen YY, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal IT, Tawfik O, LeBeau LG, Sahoo S, Vinh T, Chien AJ, Forero-Torres A, Stringer-Reasor E, Wallace AM, Pusztai L, Boughey JC, Ellis ED, Elias AD, Lu J, Lang JE, Han HS, Clark AS, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Park JW, Liu MC, Olopade O, Leyland-Jones B, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton NM, Van't Veer LJ, Perlmutter J, Melisko ME, Wilson A, Peterson G, Asare AL, Buxton MB, Paoloni M, Clennell JL, Hirst GL, Singhrao R, Steeg K, Matthews JB, Asare SM, Sanil A, Berry SM, Esserman LJ, Berry DA. Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1355-1362. doi: 10.1001/jamaoncol.2020.2535.

  PMID: 32701140 DERIVED

• Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.

  PMID: 32450725 DERIVED

• Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van 't Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020 May 1;6(5):676-684. doi: 10.1001/jamaoncol.2019.6650.

  PMID: 32053137 DERIVED

• Chien AJ, Tripathy D, Albain KS, Symmans WF, Rugo HS, Melisko ME, Wallace AM, Schwab R, Helsten T, Forero-Torres A, Stringer-Reasor E, Ellis ED, Kaplan HG, Nanda R, Jaskowiak N, Murthy R, Godellas C, Boughey JC, Elias AD, Haley BB, Kemmer K, Isaacs C, Clark AS, Lang JE, Lu J, Korde L, Edmiston KK, Northfelt DW, Viscusi RK, Yee D, Perlmutter J, Hylton NM, Van't Veer LJ, DeMichele A, Wilson A, Peterson G, Buxton MB, Paoloni M, Clennell J, Berry S, Matthews JB, Steeg K, Singhrao R, Hirst GL, Sanil A, Yau C, Asare SM, Berry DA, Esserman LJ; I-SPY 2 Consortium. MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial. J Clin Oncol. 2020 Apr 1;38(10):1059-1069. doi: 10.1200/JCO.19.01027. Epub 2019 Feb 7.

  PMID: 32031889 DERIVED

• Severson TM, Wolf DM, Yau C, Peeters J, Wehkam D, Schouten PC, Chin SF, Majewski IJ, Michaut M, Bosma A, Pereira B, Bismeijer T, Wessels L, Caldas C, Bernards R, Simon IM, Glas AM, Linn S, van 't Veer L. The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting. Breast Cancer Res. 2017 Aug 25;19(1):99. doi: 10.1186/s13058-017-0861-2.

  PMID: 28851423 DERIVED

• Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. doi: 10.1056/NEJMoa1513749.

  PMID: 27406347 DERIVED

• Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive Randomization of Neratinib in Early Breast Cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. doi: 10.1056/NEJMoa1513750.

  PMID: 27406346 DERIVED

Related Links

• I-SPY 2 TRIAL Website
• Abstract S5-02 SABCC 2014
• Abstract CT227 AACR 2014
• Abstract P1-14-03; SABCC 2015

MeSH Terms

Conditions

Breast Neoplasms; Hemangiosarcoma; Triple Negative Breast Neoplasms; Neoplasms; Pathologic Complete Response

Interventions

Standard of Care; Paclitaxel; Doxorubicin; trebananib; Trastuzumab; ganitumab; MK 2206; Ado-Trastuzumab Emtansine; pertuzumab; STA 9090; veliparib; neratinib; pexidartinib; talazoparib; Irinotecan; patritumab; SGN-LIV1A; durvalumab; olaparib; pembrolizumab; tucatinib; cemiplimab; trilaciclib; trastuzumab duocarmazine; dostarlimab; Carboplatin; abemaciclib; Letrozole; ARX788; zanidatamab; Lasofoxifene; 4-hydroxy-N-desmethyltamoxifen; niraparib; sarilumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Laura Esserman, MD, MBA

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Won Chang

CONTACT

(855) 866-0505; w.chang@quantumleaphealth.org

Heather Prisant

CONTACT

h.prisant@qlhc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2009
• First Posted: January 5, 2010
• Study Start: March 1, 2010
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (42)