NCT01042379

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5,000 (estimated)
• Sponsor: QuantumLeap Healthcare Collaborative · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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
DRUG	AMG 386 with or without Trastuzumab	Arm is closed.
DRUG	AMG 479 (Ganitumab) plus Metformin	Arm is closed.
DRUG	MK-2206 with or without Trastuzumab	Arm is closed.
DRUG	AMG 386 and Trastuzumab	Arm is closed.
DRUG	T-DM1 and Pertuzumab	Arm is closed.
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
DRUG	Ganetespib	Arm is closed.
DRUG	ABT-888	Arm is closed.
DRUG	Neratinib	Arm is closed.
DRUG	PLX3397	Arm is closed.
DRUG	Pembrolizumab - 4 cycle	Arm is closed.
DRUG	Talazoparib plus Irinotecan	Arm is closed.
DRUG	Patritumab and Trastuzumab	Arm is closed.
DRUG	Pembrolizumab - 8 cycle	Arm is closed.
DRUG	SGN-LIV1A	Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
DRUG	Durvalumab plus Olaparib	Arm is closed.
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
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
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
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
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
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
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
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
DRUG	Amcenestrant	Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks.
DRUG	Amcenestrant + Abemaciclib	Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
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
DRUG	ARX788	Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
DRUG	ARX788 + Cemiplimab	Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
DRUG	VV1 + Cemiplimab	Arm is closed. VV1, 3x10\^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
DRUG	Datopotamab deruxtecan	Arm is closed. Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
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
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.
DRUG	Lasofoxifene	Arm is closed. Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
DRUG	Z-endoxifen	Arm is closed. Z-endoxifen: 10 mg QD, p.o., for 24 weeks
DRUG	ARV-471	Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks.
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
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
DRUG	Endoxifen + Abemaciclib	Z-endoxifen: 80 mg QD, p.o., for 24 weeks Abemaciclib: 150 mg BID, p.o, for 20 weeks
DRUG	Rilvegostomig + TDXd	Arm closed to accrual Rilvegostomig: 750mg IV Q3W for 12 weeks TDXd: 5.4 mg/kg IV Q3W for 12 weeks
DRUG	Dan222 + Niraparib	Arm is closed. DAN222: 8mg/m2 IV QW for 12 weeks Niraparib: 200mg QD p.p., 12 weeks
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
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.
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.

Timeline

• Start date: 2010-03-01
• Primary completion: 2030-12-01
• Completion: 2031-12-01
• First posted: 2010-01-05
• Last updated: 2026-03-13

Locations

42 sites across 1 country: United States