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

QuantumLeap Healthcare Collaborative

Status and phase

Enrolling

Phase 2

Conditions

Angiosarcoma

Breast Tumors

Breast Cancer

TNBC - Triple-Negative Breast Cancer

Hormone Receptor Negative Tumor

Locally Advanced Breast Cancer

Early-stage Breast Cancer

Hormone Receptor Positive Tumor

HER2-positive Breast Cancer

Breast Neoplasms

HER2-negative Breast Cancer

Treatments

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

Drug: Lasofoxifene

Drug: ARX788 + Cemiplimab

Drug: Cemiplimab plus REGN3767

Drug: Sarilumab + Cemiplimab + Paclitaxel

Drug: AMG 386 with or without Trastuzumab

Drug: Pembrolizumab - 8 cycle

Drug: ARX788

Drug: ARV-471 + Abemaciclib

Drug: Endoxifen + Abemaciclib

Drug: PLX3397

Drug: MK-2206 with or without Trastuzumab

Drug: Amcenestrant + Abemaciclib

Drug: Amcenestrant

Drug: Durvalumab plus Olaparib

Drug: Pertuzumab and Trastuzumab

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

Drug: SGN-LIV1A

Drug: Tucatinib plus trastuzumab and pertuzumab

Drug: AMG 386 and Trastuzumab

Drug: SD-101 + Pembrolizumab

Drug: Dan222 + Niraparib

Drug: Rilvegostomig + TDXd

Drug: AMG 479 (Ganitumab) plus Metformin

Drug: Datopotamab deruxtecan + Durvalumab

Drug: SYD985 ([vic-]trastuzumab duocarmazine)

Drug: ARV-471

Drug: Talazoparib plus Irinotecan

Drug: Z-endoxifen

Drug: Pembrolizumab - 4 cycle

Drug: Neratinib

Drug: VV1 + Cemiplimab

Drug: Ganetespib

Drug: ARV-471 + Letrozole

Drug: Patritumab and Trastuzumab

Drug: T-DM1 and Pertuzumab

Drug: Cemiplimab

Drug: Amcenestrant + Letrozole

Drug: Standard Therapy

Drug: ABT-888

Drug: Trilaciclib with or without trastuzumab + pertuzumab

Drug: Zanidatamab

Drug: Datopotamab deruxtecan

Study type

Interventional

Funder types

Other

Identifiers

NCT01042379

097517

Details and patient eligibility

About

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.

Full 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.

Enrollment

5,000 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

5,000 participants in 42 patient groups

Standard Therapy

Active Comparator group

Description:

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

Treatment:

Drug: Standard Therapy

AMG 386 with or without Trastuzumab

Experimental group

Description:

Arm is closed.

Treatment:

Drug: AMG 386 and Trastuzumab

Drug: AMG 386 with or without Trastuzumab

AMG 479 plus Metformin

Other group

Description:

Arm is closed.

Treatment:

Drug: AMG 479 (Ganitumab) plus Metformin

MK-2206 with or without Trastuzumab

Experimental group

Description:

Arm is closed.

Treatment:

Drug: MK-2206 with or without Trastuzumab

T-DM1 and Pertuzumab

Experimental group

Description:

Arm is closed.

Treatment:

Drug: T-DM1 and Pertuzumab

Pertuzumab and Trastuzumab

Active Comparator group

Description:

Novel Control Investigational Agent. Arm is closed.

Treatment:

Drug: Pertuzumab and Trastuzumab

Ganetespib

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Ganetespib

ABT-888

Other group

Description:

Arm is closed.

Treatment:

Drug: ABT-888

Neratinib

Other group

Description:

Arm is closed.

Treatment:

Drug: Neratinib

PLX3397

Experimental group

Description:

Arm is closed.

Treatment:

Drug: PLX3397

Pembrolizumab 4 cycle

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Pembrolizumab - 4 cycle

Talazoparib plus Irinotecan

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Talazoparib plus Irinotecan

Patritumab with or without Trastuzumab

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Patritumab and Trastuzumab

Pembrolizumab 8 cycle

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Pembrolizumab - 8 cycle

SGN-LIV1A

Experimental group

Description:

Arm is closed.

Treatment:

Drug: SGN-LIV1A

Durvalumab plus Olaparib

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Durvalumab plus Olaparib

SD-101 + Pembrolizumab

Experimental group

Description:

Arm is closed.

Treatment:

Drug: SD-101 + Pembrolizumab

Tucatinib

Experimental group

Description:

Arm is closed.

Treatment:

Drug: Tucatinib plus trastuzumab and pertuzumab

Cemiplimab

Experimental group

Description: