PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC (NeoADAPT)

A Pilot Study of Neoadjuvant Response-Adapted Chemotherapy With Pembrolizumab in Patients With Stage 2 and 3 Triple Negative Breast Cancer to Determine Early PET and Biomarker Dynamics

Eligible patients with stage 2 and 3 triple negative breast cancer will be treated with 4 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab. A PET scan will be performed at baseline and after 1 cycle of therapy. A breast MRI will be performed after treatment completion. Patients with complete clinical response will proceed to surgery. Patients with clinical residual disease will complete neoadjuvant rescue with 4 cycles of doxorubicin/cyclophosphamide prior to surgery. If residual disease identified after surgery, adjuvant therapy to be determined by the treating oncologist (may include doxorubicin/cyclophosphamide/pembrolizumab, capecitabine etc).

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Olaparib; Drug: Capecitabine

Detailed Description

Eligible participants will undergo baseline procedures including research bloodwork, MRI and PET scan. Participants will then be treated with one cycle of paclitaxel, carboplatin and pembrolizumab (TCarbo/pembro). At the end of Cycle one patients will undergo repeat procedures (bloodwork and PET scan), and then continue with treatment for an additional three cycles. ctDNA will be collected on day 1 of each cycle. At the end of treatment patients will undergo repeat MRI.

Patients achieving a clinical complete response (CR) on MRI will proceed with surgery. Patients with clinical residual disease (RD) on MRI will be recommended a biopsy, and be recommended "rescue" neoadjuvant doxorubicin and cyclophosphamide with pembrolizumab (AC/pembro) for four additional cycles, and then proceed with surgery. Note: patients/treating physician may opt to proceed with surgery.

Archival tissue will be collected from the surgical product. Patients achieving a pathologic CR (pCR) may proceed with adjuvant pembrolizumab per standard of care, and treating physician's discretion. Patients with pathological RD may proceed with "rescue" adjuvant AC/pembrolizumab for four additional cycles (if not given neoadjuvantly), per treating physician discretion. The participants may also receive Aadjuvant capecitabine or olaparib as indicated and per treating physician's discretion.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hopkins Breast Trials; Phone Number: 410-614-1361; Email: HopkinsBreastTrials@jhmi.edu
• Study Contact Backup: Name: Cesar A Santa-Maria, MD; Phone Number: 410-614-0874; Email: csantam2@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Contact: JHCCCRO; Phone Number: 410-955-8866; Email: jhcccro@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stage II-III TNBC - estrogen receptor (ER) and progesterone receptor (PR) up to and including 10% is eligible
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

4. Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:

   1. Adequate marrow and organ function
   2. Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
5. Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

1. Patients unable to undergo PET or MRI
2. Evidence of metastatic disease or loco-regional recurrence (i.e. distant or chest wall recurrence)
3. Inflammatory breast cancer
4. Previous treatment with paclitaxel, carboplatin, or immune checkpoint inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant therapy; 4 cycles of paclitaxel/carboplatin/pembrolizumab

Drug: Carboplatin; chemotherapy; Other Names: Paraplatin; Drug: Paclitaxel; chemotherapy; Other Names: Taxol; Drug: Pembrolizumab; immunotherapy; Other Names: Keytruda; Drug: Doxorubicin; additional chemotherapy - neoadjuvant or adjuvant rescue; Other Names: Adriamycin; Drug: Cyclophosphamide; additional chemotherapy - adjuvant rescue; Other Names: Cytoxan; Drug: Olaparib; adjuvant rescue; Other Names: Lynparza; Drug: Capecitabine; adjuvant rescue; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SULmax in relation to pCR	Evaluate if lack of decrease in fluorodeooxyglucose (FDG) / positron emission tomography (PET) standardized uptake value corrected for lean body mass (SULmax) by <40% after 1 cycle of neoadjuvant therapy correlates with residual disease at the time of surgery.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR)	Evaluate the pathologic complete response (pCR) rate in patients with early-stage triple negative breast cancer (TNBC) treated with neoadjuvant chemo-immunotherapy.	3 years
Circulating tumor deoxyribonucleic acid (ctDNA) clearance	Evaluate how circulating tumor deoxyribonucleic acid (ctDNA) kinetics collected at pre-treatment, and during and after completion of neoadjuvant treatment correlate with pathologic complete response (pCR) at the time of surgery.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR) comparison	Compare the pathologic complete response (pCR) rates among patients who achieved clinical complete response (cCR) by breast magnetic resonance imaging (MRI) and those received "rescue" neoadjuvant AC/pembrolizumab with clinical residual disease (RD) after MRI scan.	3 years
Diagnostic accuracy of percent and absolute change between baseline and C1D15 measurements	Evaluate the diagnostic accuracy of percent and absolute change (between baseline and C1D15 measurements), and C1D15 absolute measurements in fluorodeooxyglucose (FDG) / positron emission tomography (PET) standardized uptake value corrected for lean body mass (SULmax) for predicting clinical complete response (cCR) using receiver operating characteristic (ROC) curve.	3 years
Clinical complete response (cCR) and pathologic complete response (pCR)	Investigate if clinical complete response (cCR) by MRI is predictive of pathologic complete response (pCR).	3 years
Change in microbiome	Number of patients that experienced changes in the microbiome serially over time of residual disease.	3 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Breast Cancer Research Foundation
• Investigators: Study Chair: Cesar A Santa-Maria, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. Epub 2020 Sep 20.
• Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant; triple negative
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Uracil; Pyrimidinones; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Deoxyribonucleosides; Fluorouracil; Capecitabine; Cyclophosphamide; Carboplatin; Doxorubicin; Paclitaxel; pembrolizumab; olaparib
• Other Study ID Numbers: J2395; IRB00398141 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No