Neoadjuvant TIL- and Response-Adapted Chemoimmunotherapy for TNBC

NCT05645380 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00149312
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 7

Brief Summary

This study will assess if the presence of immune system cells in and around the tumor impacts tumor shrinkage in patients receiving neoadjuvant chemoimmunotherapy for triple-negative breast cancer.

Conditions

Triple Negative Breast Cancer; Breast Cancer

Keywords

Tumor infiltrating lymphocytes; Neoadjuvant chemotherapy; Neoadjuvant immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate in high sTIL cohort with radiographic complete response

  Defined as percentage of participants who achieve pathological complete response in the breast and axilla. Pathological complete response is defined as no evidence of invasive disease in the breast (residual DCIS permitted) and axilla at the time of pathology review.

  Up to 26 weeks

Secondary Outcomes (4)

• Residual cancer burden (RCB) 0+1 rate in high sTIL cohort with radiographic complete response

  Up to 26 weeks

• pCR and RCB 0+1 in intermediate sTIL cohort

  Up to 26 weeks

• pCR and RCB 0+1 in low sTIL cohort

  Up to 32 weeks

• Recurrence-free, event-free, and overall survival

  Up to 5 years

Study Arms (3)

High sTILs (≥30%)

ACTIVE COMPARATOR

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for four cycles.

Drug: Carboplatin; Drug: Docetaxel; Drug: Pembrolizumab

Intermediate sTILs (5-29%)

ACTIVE COMPARATOR

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for six cycles.

Drug: Carboplatin; Drug: Docetaxel; Drug: Pembrolizumab

Low sTILs (<5%)

ACTIVE COMPARATOR

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for four cycles followed by Doxorubicin (60 mg/m2) + Cyclophosphamide (600 mg/m2) + Pembrolizumab (200 mg) every 14 or 21 days for four cycles.

Drug: Carboplatin; Drug: Docetaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pembrolizumab

Interventions

Carboplatin DRUG

AUC=6, IV

Also known as: Paraplatin

High sTILs (≥30%); Intermediate sTILs (5-29%); Low sTILs (<5%)

Docetaxel DRUG

75 mg/m2, IV

Also known as: Taxotere

High sTILs (≥30%); Intermediate sTILs (5-29%); Low sTILs (<5%)

Doxorubicin DRUG

60 mg/m2, IV

Also known as: Adriamycin

Low sTILs (<5%)

Cyclophosphamide DRUG

600 mg/m2, IV

Also known as: Cytoxan

Low sTILs (<5%)

Pembrolizumab DRUG

200 mg, IV

Also known as: Keytruda

High sTILs (≥30%); Intermediate sTILs (5-29%); Low sTILs (<5%)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Female subjects 18 years of age or older
• Histologically confirmed cT1c-T3N0, cT1-T3N1-N2, cTxN1-2 TNBC
• The invasive tumor must be hormone receptor poor, defined as both estrogen receptor (ER) and progesterone receptor staining in ≤ 10% of invasive cancer cells by IHC
• The invasive tumor must be HER2-negative based on the current ASCO-CAP guidelines
• No previous ipsilateral breast surgery for the current breast cancer
• No previous chemotherapy, immunotherapy, endocrine therapy, or radiotherapy for the current breast cancer
• ECOG Performance Status 0 - 1 documented within 21 days prior to the start of study treatment
• Breast and axillary imaging (including ultrasound and MRI) within 42 days (6 weeks) prior to treatment initiation
• Subjects with clinically and/or radiographically abnormal axillary or internal mammary lymph nodes should have pathologic confirmation of disease status with image-guided biopsy or fine needle aspiration
• Archival breast tumor tissue has been obtained or has been requested for use
• No clinically apparent metastatic disease. Staging to rule out metastatic disease is suggested for patients with clinical TNM stage III disease
• Subjects with bilateral synchronous TNBC are eligible if they meet other eligibility criteria
• No baseline neuropathy greater than grade 2
• Patients are not pregnant, not breastfeeding, and either not a woman of childbearing potential or agrees to follow specific contraceptive guidelines during the treatment period and for at least 120 days after the last dose of study treatment

You may not qualify if:

• Current or anticipated use of other investigational agents while participating in this study
• Subject has previously received chemotherapy, immunotherapy, endocrine therapy, radiotherapy, or surgery for this breast cancer
• Subject has clinically or radiographically detected metastatic disease
• Subject has inflammatory breast cancer
• Subject has a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen. Note: Patients with squamous cell or basal cell carcinoma of the skin, ductal carcinoma in situ (DCIS) of the breast, or carcinoma in situ (CIS) of the uterine cervix who have undergone definitive therapy are not excluded from participation
• History of allergic reactions attributed to doxorubicin, cyclophosphamide, carboplatin, or docetaxel
• History of severe (≥ grade 3) hypersensitivity to pembrolizumab or any of its excipients
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 inhibitor or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40, CD137)
• If participant has received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Subject has received a live vaccine within 30 days prior to treatment initiation
• Subject is currently receiving treatment or has received treatment with an investigational agent within four weeks prior to treatment initiation, or has used an investigational device within four weeks prior to treatment initiation
• Has a diagnosis of immunodeficiency or is receiving chronic steroid therapy (in doses exceeding 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
• Active autoimmune disease that has required systemic treatment (e.g., disease-modifying agents, corticosteroids, immunosuppressive drugs) in the past two years. Note: Patients using replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy) are eligible
• Currently has or has history of (within the past one year) non-infectious pneumonitis requiring steroids
• Active infection requiring systemic therapy

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (7)

The University of Kansas Cancer Center - Clinical Research Center

Fairway, Kansas, 66205, United States

Location

The University of Kansas Cancer Center - Main Hospital

Kansas City, Kansas, 66160, United States

Location

The University of Kansas Cancer Center - Westwood

Kansas City, Kansas, 66205, United States

Location

The University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

The University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

The University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Carboplatin; Docetaxel; Doxorubicin; Cyclophosphamide; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Priyanka Sharma, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 9, 2022
• Study Start: December 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (7)