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

NCT ID: NCT01042379

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 5000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-01
• Study Completion Date: 2031-12-31

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.

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Therapy

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

Group Type: ACTIVE_COMPARATOR

Standard Therapy

Intervention Type: 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

AMG 386 with or without Trastuzumab

Arm is closed.

Group Type: EXPERIMENTAL

AMG 386 with or without Trastuzumab

Intervention Type: DRUG

Arm is closed.

AMG 386 and Trastuzumab

Intervention Type: DRUG

Arm is closed.

AMG 479 plus Metformin

Arm is closed.

Group Type: OTHER

AMG 479 (Ganitumab) plus Metformin

Intervention Type: DRUG

Arm is closed.

MK-2206 with or without Trastuzumab

Arm is closed.

Group Type: EXPERIMENTAL

MK-2206 with or without Trastuzumab

Intervention Type: DRUG

Arm is closed.

T-DM1 and Pertuzumab

Arm is closed.

Group Type: EXPERIMENTAL

T-DM1 and Pertuzumab

Intervention Type: DRUG

Arm is closed.

Pertuzumab and Trastuzumab

Arm is closed. Novel Control Investigational Agent.

Group Type: ACTIVE_COMPARATOR

Pertuzumab and Trastuzumab

Intervention Type: 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

Ganetespib

Arm is closed.

Group Type: EXPERIMENTAL

Ganetespib

Intervention Type: DRUG

Arm is closed.

ABT-888

Arm is closed.

Group Type: OTHER

ABT-888

Intervention Type: DRUG

Arm is closed.

Neratinib

Arm is closed.

Group Type: OTHER

Neratinib

Intervention Type: DRUG

Arm is closed.

PLX3397

Arm is closed.

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Arm is closed.

Pembrolizumab 4 cycle

Arm is closed.

Group Type: EXPERIMENTAL

Pembrolizumab - 4 cycle

Intervention Type: DRUG

Arm is closed.

Talazoparib plus Irinotecan

Arm is closed.

Group Type: EXPERIMENTAL

Talazoparib plus Irinotecan

Intervention Type: DRUG

Arm is closed.

Patritumab with or without Trastuzumab

Arm is closed.

Group Type: EXPERIMENTAL

Patritumab and Trastuzumab

Intervention Type: DRUG

Arm is closed.

Pembrolizumab 8 cycle

Arm is closed.

Group Type: EXPERIMENTAL

Pembrolizumab - 8 cycle

Intervention Type: DRUG

Arm is closed.

SGN-LIV1A

Arm is closed.

Group Type: EXPERIMENTAL

SGN-LIV1A

Intervention Type: DRUG

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

Durvalumab plus Olaparib

Arm is closed.

Group Type: EXPERIMENTAL

Durvalumab plus Olaparib

Intervention Type: DRUG

Arm is closed.

SD-101 + Pembrolizumab

Arm is closed.

Group Type: EXPERIMENTAL

SD-101 + Pembrolizumab

Intervention Type: 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

Arm is closed.

Group Type: EXPERIMENTAL

Tucatinib plus trastuzumab and pertuzumab

Intervention Type: 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

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Cemiplimab

Intervention Type: 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

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Cemiplimab plus REGN3767

Intervention Type: 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

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Trilaciclib with or without trastuzumab + pertuzumab

Intervention Type: 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

SYD985 ([vic-]trastuzumab duocarmazine)

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

SYD985 ([vic-]trastuzumab duocarmazine)

Intervention Type: 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

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

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

Intervention Type: 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

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

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Endocrine Optimization Pilot: Amcenestrant Monotherapy

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Amcenestrant

Intervention Type: DRUG

Arm is closed.

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

Endocrine Optimization Pilot: Amcenestrant + Abemaciclib

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Amcenestrant + Abemaciclib

Intervention Type: DRUG

Arm is closed.

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

Endocrine Optimization Pilot: Amcenestrant + Letrozole

Arm is closed. Novel Investigational Agent.

Group Type: EXPERIMENTAL

Amcenestrant + Letrozole

Intervention Type: DRUG

Arm is closed.

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

ARX788 in Block A and followed by SOC in Block B

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

Group Type: EXPERIMENTAL

ARX788

Intervention Type: DRUG

Arm is closed.

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

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

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

Group Type: EXPERIMENTAL

ARX788 + Cemiplimab

Intervention Type: DRUG

Arm is closed.

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

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

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

Group Type: EXPERIMENTAL

VV1 + Cemiplimab

Intervention Type: DRUG

Arm is closed.

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

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

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

Group Type: EXPERIMENTAL

Datopotamab deruxtecan

Intervention Type: DRUG

Arm is closed.

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

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

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

Group Type: EXPERIMENTAL

Datopotamab deruxtecan + Durvalumab

Intervention Type: DRUG

Arm is closed.

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

Zanidatamab for Block ABC

Arm open for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Zanidatamab

Intervention Type: 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.

Endocrine Optimization Pilot: Lasofoxifene

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Lasofoxifene

Intervention Type: DRUG

Arm is closed.

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

Endocrine Optimization Pilot: (Z)-Endoxifen

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Z-endoxifen

Intervention Type: DRUG

Arm is closed.

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

Endocrine Optimization Pilot: ARV-471

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

ARV-471

Intervention Type: DRUG

Arm is closed.

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

Endocrine Optimization Pilot: ARV-471 + Letrozole

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

ARV-471 + Letrozole

Intervention Type: 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 + Abemaciclib

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

ARV-471 + Abemaciclib

Intervention Type: 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: (Z)-Endoxifen + Abemaciclib

Arm is open for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Endoxifen + Abemaciclib

Intervention Type: DRUG

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

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

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Rilvegostomig + TDXd

Intervention Type: DRUG

Arm closed to accrual

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

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

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Dan222 + Niraparib

Intervention Type: DRUG

Arm is closed.

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

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

Arm is closed for accrual. Novel investigational Agent.

Group Type: EXPERIMENTAL

Sarilumab + Cemiplimab + Paclitaxel

Intervention Type: 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 in Block A and followed by SOC in Block B

Arm is open for accrual. Novel Investigational Agent.

Group Type: EXPERIMENTAL

GSK 5733584

Intervention Type: 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 in Block A and followed by SOC in Block B

Arm is open for accrual. Novel Investigational Agent.

Group Type: EXPERIMENTAL

GSK 5733584 + Dostarlimab

Intervention Type: 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.

Interventions

Standard Therapy

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

Intervention Type: DRUG

AMG 386 with or without Trastuzumab

Arm is closed.

Intervention Type: DRUG

AMG 479 (Ganitumab) plus Metformin

Arm is closed.

Intervention Type: DRUG

MK-2206 with or without Trastuzumab

Arm is closed.

Intervention Type: DRUG

AMG 386 and Trastuzumab

Arm is closed.

Intervention Type: DRUG

T-DM1 and Pertuzumab

Arm is closed.

Intervention Type: DRUG

Pertuzumab and Trastuzumab

Arm is closed for Accrual.

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

Intervention Type: DRUG

Ganetespib

Arm is closed.

Intervention Type: DRUG

ABT-888

Arm is closed.

Intervention Type: DRUG

Neratinib

Arm is closed.

Intervention Type: DRUG

PLX3397

Arm is closed.

Intervention Type: DRUG

Pembrolizumab - 4 cycle

Arm is closed.

Intervention Type: DRUG

Talazoparib plus Irinotecan

Arm is closed.

Intervention Type: DRUG

Patritumab and Trastuzumab

Arm is closed.

Intervention Type: DRUG

Pembrolizumab - 8 cycle

Arm is closed.

Intervention Type: DRUG

SGN-LIV1A

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

Intervention Type: DRUG

Durvalumab plus Olaparib

Arm is closed.

Intervention Type: DRUG

SD-101 + Pembrolizumab

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

Intervention Type: DRUG

Tucatinib plus trastuzumab and pertuzumab

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

Intervention Type: DRUG

Cemiplimab

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

Intervention Type: DRUG

Cemiplimab plus REGN3767

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

Intervention Type: DRUG

Trilaciclib with or without trastuzumab + pertuzumab

Arm closed for accrual.

Trilaciclib: 240 mg/m2 IV weekly cycle 1-16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

For HER2+:

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

Intervention Type: DRUG

SYD985 ([vic-]trastuzumab duocarmazine)

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

Amcenestrant

Arm is closed.

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

Intervention Type: DRUG

Amcenestrant + Abemaciclib

Arm is closed.

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

Intervention Type: DRUG

Amcenestrant + Letrozole

Arm is closed.

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

Intervention Type: DRUG

ARX788

Arm is closed.

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

Intervention Type: DRUG

ARX788 + Cemiplimab

Arm is closed.

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

Intervention Type: DRUG

VV1 + Cemiplimab

Arm is closed.

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

Intervention Type: DRUG

Datopotamab deruxtecan

Arm is closed.

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

Intervention Type: DRUG

Datopotamab deruxtecan + Durvalumab

Arm is closed.

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

Intervention Type: DRUG

Zanidatamab

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.

Intervention Type: DRUG

Lasofoxifene

Arm is closed.

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

Intervention Type: DRUG

Z-endoxifen

Arm is closed.

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

Intervention Type: DRUG

ARV-471

Arm is closed.

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

Intervention Type: DRUG

ARV-471 + Letrozole

Arm is closed.

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

Intervention Type: DRUG

ARV-471 + Abemaciclib

Arm is closed.

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

Intervention Type: DRUG

Endoxifen + Abemaciclib

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

Intervention Type: DRUG

Rilvegostomig + TDXd

Arm closed to accrual

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

Intervention Type: DRUG

Dan222 + Niraparib

Arm is closed.

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

Intervention Type: DRUG

Sarilumab + Cemiplimab + Paclitaxel

Arm is closed to accrual.

Sarilumab: 200mg Subcutaneous injection Q2W for 12 weeks Cemiplimab: 350mg IV Q3W for 12 weeks Paclitaxel: 80 mg/m2 IV QW for 12 weeks

Intervention Type: DRUG

GSK 5733584

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.

Intervention Type: DRUG

GSK 5733584 + Dostarlimab

Arm is open for accrual.

GSK 5733584 Route: Intravenous Infusion Dosage Form: 4.8 mg/kg intravenous Q3W for injection x 12 weeks max.

Dostarlimab Route: Intravenous Infusion Dosage Form: 500 mg fixed dose intravenous Q3W for infusion x 12 weeks max.

Intervention Type: DRUG

Other Intervention Names

Paclitaxel (Taxol); Doxorubicin (Adriamycin); AMG 386 (Trebananib); (Trastuzumab) Herceptin; Ganitumab; (Trastuzumab) Herceptin; AMG 386 (Trebananib); Trastuzumab (Herceptin); T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta); Pertuzumab (Perjeta); Trastuzumab (Herceptin); Veliparib; Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin); Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin); Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin); SAR439859; Amcenestrant (SAR439859), Abemaciclib (Verzenio); Amcenestrant (SAR439859), Letrozole (Femara); VOYAGER V1™; VSV-IFNβ-NIS; Dato-DXd; Dato-DXd

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

QuantumLeap Healthcare Collaborative

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura Esserman, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

Site Status: NOT_YET_RECRUITING

University of Arizona

Tucson, Arizona, United States

Site Status: ACTIVE_NOT_RECRUITING

University of California - Davis, Comprehensive Cancer Center

Davis, California, United States

Site Status: RECRUITING

City of Hope

Duarte, California, United States

Site Status: RECRUITING

University of California San Diego

La Jolla, California, United States

Site Status: RECRUITING

University of Southern California

Los Angeles, California, United States

Site Status: RECRUITING

HOAG Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status: RECRUITING

University of California San Francisco (UCSF)

San Francisco, California, United States

Site Status: RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status: RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

Site Status: RECRUITING

Georgetown University Medical Center

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

Site Status: RECRUITING

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status: RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status: RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status: RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Loyola University

Maywood, Illinois, United States

Site Status: RECRUITING

University of Kansas

Westwood, Kansas, United States

Site Status: ACTIVE_NOT_RECRUITING

Herbert-Herman Cancer Center, Sparrow Hospital

Lansing, Michigan, United States

Site Status: RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status: RECRUITING

Metro Minnesota Community Oncology Research Consortium, Hennepin County Medical Center

Saint Louis Park, Minnesota, United States

Site Status: RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status: RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status: RECRUITING

Laura and Isaac Perlmutter Cancer Center / NYU Langone Health

New York, New York, United States

Site Status: RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status: RECRUITING

University of Rochester Wilmot Cancer Institute

Rochester, New York, United States

Site Status: RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status: RECRUITING

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

The Ohio State University, Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, United States

Site Status: RECRUITING

Oregon Health & Science Institute (OHSU)

Portland, Oregon, United States

Site Status: RECRUITING

University of Pennsylvania (U Penn)

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

University Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status: ACTIVE_NOT_RECRUITING

Sanford Clinical Research

Sioux Falls, South Dakota, United States

Site Status: RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Texas, Southwestern Medical Center

Dallas, Texas, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Texas, M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status: ACTIVE_NOT_RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status: RECRUITING

Inova Health System

Falls Church, Virginia, United States

Site Status: ACTIVE_NOT_RECRUITING

Swedish Cancer Institute

Seattle, Washington, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Washington

Seattle, Washington, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Won Chang

Role: CONTACT

w.chang@quantumleaphealth.org

(855) 866-0505

Maria Pitsiouni, PhD

Role: CONTACT

m.pitsiouni@quantumleaphealth.org

Facility Contacts

Role: primary

507-538-7623

Role: primary

800-826-4673

Role: primary

858-822-6194

Role: backup

CancerCTO@ucsd.edu

858-822-6194

Kristy Watkins, RN

Role: primary

Watkins_K@ccnt.usc.edu

323-865-0452

Role: primary

415-443-4296

Role: primary

720-848-1622

Trisha Burello, MS

Role: primary

trisha.burrello@yale.edu

203-737-2848

Minetta Liu, MD

Role: primary

Liumc@georgetown.edu

202-444-3677

Role: primary

773-834-2756

Role: primary

708-327-3102

Role: primary

612-626-8487

Role: primary

507-538-7623

Role: primary

732-235-7356

Yannis Karamitas

Role: primary

Yannis.Karamitas@nyulangone.org

Role: primary

WCICTOResearch@urmc.rochester.edu

Angela Howell, MD

Role: primary

anhowell@wakehealth.edu

336-716-5440

Role: primary

800-233-2273

Brienna Palm

Role: primary

palmb@ohsu.edu

503-494-4438

Role: backup

503-494-8573

Role: primary

215-614-1850

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Related Links

http://www.ispy2.org

I-SPY 2 TRIAL Website

http://d3ciwvs59ifrt8.cloudfront.net/6cac4f3d-e0de-4924-9f2a-9b5b95ea9a0d/25399142-2af5-4a8e-8a21-184e5fc141c7.pdf

Abstract S5-02 SABCC 2014

http://d3ciwvs59ifrt8.cloudfront.net/6cac4f3d-e0de-4924-9f2a-9b5b95ea9a0d/e8745ff8-6e60-412c-8e14-930a42d1f477.pdf

Abstract CT227 AACR 2014

http://d3ciwvs59ifrt8.cloudfront.net/6cac4f3d-e0de-4924-9f2a-9b5b95ea9a0d/30b6e099-e50c-48dd-a733-2ecb9f7bc6a3.pdf

Abstract P1-14-03; SABCC 2015

Other Identifiers

097517

Identifier Type: -

Identifier Source: org_study_id