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

Conditions

• Angiosarcoma
• Breast Cancer
• Breast Neoplasms
• Breast Tumors
• Early-stage Breast Cancer
• HER2-negative Breast Cancer
• HER2-positive Breast Cancer
• Hormone Receptor Negative Tumor
• Hormone Receptor Positive Tumor
• Locally Advanced Breast Cancer
• TNBC - Triple-Negative Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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
• AMG 386 with or without Trastuzumab — DRUG
  Arm is closed.
• AMG 479 (Ganitumab) plus Metformin — DRUG
  Arm is closed.
• MK-2206 with or without Trastuzumab — DRUG
  Arm is closed.
• AMG 386 and Trastuzumab — DRUG
  Arm is closed.
• T-DM1 and Pertuzumab — DRUG
  Arm is closed.
• 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
• Ganetespib — DRUG
  Arm is closed.
• ABT-888 — DRUG
  Arm is closed.
• Neratinib — DRUG
  Arm is closed.
• PLX3397 — DRUG
  Arm is closed.
• Pembrolizumab - 4 cycle — DRUG
  Arm is closed.
• Talazoparib plus Irinotecan — DRUG
  Arm is closed.
• Patritumab and Trastuzumab — DRUG
  Arm is closed.
• Pembrolizumab - 8 cycle — DRUG
  Arm is closed.
• SGN-LIV1A — DRUG
  Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
• Durvalumab plus Olaparib — DRUG
  Arm is closed.
• SD-101 + Pembrolizumab — DRUG
  Arm is closed. SD-101: IT injection 2 mg/ml (1 ml for T2 tumors, 2 ml for \>T3 tumors) weekly x 4, then every 3 weeks x 2 cycles 1,2,3,4,7,10 Pembrolizumab: 200mg IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
• Tucatinib plus trastuzumab and pertuzumab — DRUG
  Arm is closed. Tucatinib: 300 mg PO BID 12 weeks CLOSED Tucatinib: 250 mg PO BID 12 weeks CLOSED Tucatinib adaptive: 150mg BID days 1-28, 250mg BID days 29-84 Trastuzumab: 4 mg/kg IV (loading dose) cycle 1; 2 mg/kg (thereafter) cycles 2-12 Pertuzumab: 840 mg IV (loading dose) cycle 1; 420 mg (thereafter) cycles 4, 7 and 10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
• Cemiplimab — DRUG
  Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
• Cemiplimab plus REGN3767 — DRUG
  Arm is closed. Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 REGN 3767: 1600 mg q3W X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
• Trilaciclib with or without trastuzumab + pertuzumab — DRUG
  Arm closed for accrual. Trilaciclib: 240 mg/m2 IV weekly cycle 1-16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles For HER2+: Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
• SYD985 ([vic-]trastuzumab duocarmazine) — DRUG
  Arm is closed. SYD985: 1.2 mg/kg IV (q3w x 12 weeks) cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
• Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab — DRUG
  Arm is closed. For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle
• 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
• Amcenestrant — DRUG
  Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks.
• Amcenestrant + Abemaciclib — DRUG
  Arm is closed. Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
• 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
• ARX788 — DRUG
  Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
• ARX788 + Cemiplimab — DRUG
  Arm is closed. ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
• VV1 + Cemiplimab — DRUG
  Arm is closed. VV1, 3x10\^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
• Datopotamab deruxtecan — DRUG
  Arm is closed. Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
• 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
• Zanidatamab — DRUG
  Zanidatamab: IV Infusion at a 2-tiered flat dose. 1,800mg (\<70 kg) and 2400mg (≥70 kg). Neoadjuvant doing of zanidatamab: The initial dose will be administered on Cycle 1 Day 1, with Cycle 2 Day 1 occurring 14 days thereafter, followed by subsequent dosing every 3 weeks (Q3W) for a total of up to 5 doses in block A, up to 4 doses Block B, up to 5 doses Block C. Adjuvant dosing of zanidatamab: Administered every 3 weeks (Q3W) for a total of 1 year of HER2 based therapy. The total number of adjuvant weeks will be dependent on the number of weeks of exposure of zanidatamab in Blocks A, B, and C.
• Lasofoxifene — DRUG
  Arm is closed. Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
• Z-endoxifen — DRUG
  Arm is closed. Z-endoxifen: 10 mg QD, p.o., for 24 weeks
• ARV-471 — DRUG
  Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks.
• ARV-471 + Letrozole — DRUG
  Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks
• ARV-471 + Abemaciclib — DRUG
  Arm is closed. ARV-471: 200 mg QD, p.o, for 24 weeks Abemaciclib: 150 mg BID, p.o, for 24 weeks
• Endoxifen + Abemaciclib — DRUG
  Z-endoxifen: 80 mg QD, p.o., for 24 weeks Abemaciclib: 150 mg BID, p.o, for 20 weeks
• Rilvegostomig + TDXd — DRUG
  Arm closed to accrual Rilvegostomig: 750mg IV Q3W for 12 weeks TDXd: 5.4 mg/kg IV Q3W for 12 weeks
• Dan222 + Niraparib — DRUG
  Arm is closed. DAN222: 8mg/m2 IV QW for 12 weeks Niraparib: 200mg QD p.p., 12 weeks
• Sarilumab + Cemiplimab + Paclitaxel — DRUG
  Arm is closed to accrual. Sarilumab: 200mg Subcutaneous injection Q2W for 12 weeks Cemiplimab: 350mg IV Q3W for 12 weeks Paclitaxel: 80 mg/m2 IV QW for 12 weeks
• GSK 5733584 — DRUG
  Arm is open for accrual. Route: Intravenous infusion Dosage Form: 4.8 mg/kg intravenous Q3W for injection. Will receive a max of 12 weeks.
• GSK 5733584 + Dostarlimab — DRUG
  Arm is open for accrual. GSK 5733584 Route: Intravenous Infusion Dosage Form: 4.8 mg/kg intravenous Q3W for injection x 12 weeks max. Dostarlimab Route: Intravenous Infusion Dosage Form: 500 mg fixed dose intravenous Q3W for infusion x 12 weeks max.
• Ivonescimab (20mg/kg Q3W) — DRUG
  Strengths to be used in trial: 1. 20 mg/kg IV Q3W monotherapy 2. 20 mg/kg IV Q3W with paclitaxel 3. 20 mg/kg IV Q3W with carboplatin and paclitaxel. Standard Regimen: 20 mg/kg IV Q3W. Patients in Block A will receive a minimum of 6 weeks a maximum of 12 weeks of Ivonescimab monotherapy in Block A. Patients that have completed Block A, may receive ivonescimab plus paclitaxel or ivonescimab plus paclitaxel plus carboplatin in Block B (depending on subtype).

Study Details

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.

Key Dates

Start date

Mar 1, 2010

Status verified

May 2026

Primary completion

Dec 31, 2030

Completion

Dec 31, 2031

Study Design

Enrollment

5,000 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Standard Therapy
  Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
• Experimental: AMG 386 with or without Trastuzumab
  Arm is closed.
• Other: AMG 479 plus Metformin
  Arm is closed.
• Experimental: MK-2206 with or without Trastuzumab
  Arm is closed.
• Experimental: T-DM1 and Pertuzumab
  Arm is closed.
• Active Comparator: Pertuzumab and Trastuzumab
  Arm is closed. Novel Control Investigational Agent.
• Experimental: Ganetespib
  Arm is closed.
• Other: ABT-888
  Arm is closed.
• Other: Neratinib
  Arm is closed.
• Experimental: PLX3397
  Arm is closed.
• Experimental: Pembrolizumab 4 cycle
  Arm is closed.
• Experimental: Talazoparib plus Irinotecan
  Arm is closed.
• Experimental: Patritumab with or without Trastuzumab
  Arm is closed.
• Experimental: Pembrolizumab 8 cycle
  Arm is closed.
• Experimental: SGN-LIV1A
  Arm is closed.
• Experimental: Durvalumab plus Olaparib
  Arm is closed.
• Experimental: SD-101 + Pembrolizumab
  Arm is closed.
• Experimental: Tucatinib
  Arm is closed.
• Experimental: Cemiplimab
  Arm is closed. Novel Investigational Agent.
• Experimental: Cemiplimab plus REGN3767
  Arm is closed. Novel Investigational Agent.
• Experimental: Trilaciclib with or without trastuzumab + pertuzumab
  Arm is closed. Novel Investigational Agent.
• Experimental: SYD985 ([vic-]trastuzumab duocarmazine)
  Arm is closed. Novel Investigational Agent.
• Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
  Arm is closed. Novel Investigational Agent.
• Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
  Arm is closed. Novel Investigational Agent.
• Experimental: Endocrine Optimization Pilot: Amcenestrant Monotherapy
  Arm is closed. Novel Investigational Agent.
• Experimental: Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
  Arm is closed. Novel Investigational Agent.
• Experimental: Endocrine Optimization Pilot: Amcenestrant + Letrozole
  Arm is closed. Novel Investigational Agent.
• Experimental: ARX788 in Block A and followed by SOC in Block B
  Arm is closed for accrual for accrual. Novel investigational Agent followed by SOC.
• Experimental: ARX788 + Cemiplimab in Block A and followed by SOC in Block B
  Arm is closed for accrual. Novel investigational Agent followed by SOC.
• Experimental: 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.
• Experimental: Datopotamab Deruxtecan in Block A and followed by SOC in block B
  Arm is closed for accrual. Novel investigational Agent followed by SOC.
• Experimental: Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
  Arm is closed for accrual. Novel investigational Agent followed by SOC.
• Experimental: Zanidatamab for Block ABC
  Arm open for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: Lasofoxifene
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: (Z)-Endoxifen
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: ARV-471
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: ARV-471 + Letrozole
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: ARV-471 + Abemaciclib
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib
  Arm is closed for accrual. Enrollment completed. Novel investigational Agent.
• Experimental: Rilvegostomig + TDXd in Block A and followed by SOC in Block B
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: DAN222 + Niraparib in Block A and followed by SOC in Block B
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block C
  Arm is closed for accrual. Novel investigational Agent.
• Experimental: GSK 5733584 in Block A and followed by SOC in Block B
  Arm is open for accrual. Novel Investigational Agent.
• Experimental: GSK 5733584 + Dostarlimab in Block A and followed by SOC in Block B
  Arm is open for accrual. Novel Investigational Agent.
• Experimental: Ivonescimab in Blocks A and B
  Open for accrual. Novel Investigational Agent.

Primary Outcome Measure

Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry. [ Time Frame: Post surgery based on upto 36-week treatment ]

Central Contacts

• Won Chang
  (855) 866-0505
  [email protected]
• Heather Prisant
  [email protected]

Locations (42)

Find similar trials in Birmingham, AL

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