Triple Negative Breast Cancer (TNBC)Phase 2NeoTILsNCT07743190
A Phase II Study of Biomarker-Guided De-escalation Using Anthracycline-Free Neoadjuvant Chemoimmunotherapy in Early-Stage Triple Negative Breast Cancer (TNBC) Patients With High Tumor-Infiltrating Lymphocytes (TILs)
A Phase 2 study testing Carboplatin, Paclitaxcel and Pembrolizumab in people with Triple Negative Breast Cancer (TNBC) and Elevated Tumor-Infiltrating Lymphocytes, run by Medical University of South Carolina at 2 sites in United States.
Trial summary
This study tests a new treatment approach for people with early-stage triple negative breast cancer whose tumors have a high number of immune cells, called tumor-infiltrating lymphocytes or TILs, as seen by a pathologist on tissue review. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer (TNBC), Elevated Tumor-Infiltrating Lymphocytes
- What is being tested?
- Carboplatin, Paclitaxcel and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2027to 29 May 2034
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pre-Screening Phase:
- Age ≥ 18 years at the time of informed consent.
- Ability to understand and willingness to sign a written informed consent document in accordance with institutional and federal guidelines.
- Histologically confirmed diagnosis of triple-negative breast cancer (TNBC) or hormone receptor-low invasive breast carcinoma, with clinical anatomic Stage II or Stage IIIA/B as defined by the AJCC 8th Edition Anatomic Breast Cancer Staging System.
- Invasive tumor must be estrogen receptor (ER) and/or progesterone receptor (PR) negative or low, defined as ≤10% positive staining by immunohistochemistry (IHC).
- HER2-negative disease, defined in accordance with current ASCO-CAP HER2 testing guidelines.
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Screening and Treatment Phases:
- General Eligibility
- Individuals of childbearing potential must be willing and able to use highly effective contraception from the time of informed consent, throughout study treatment, and for at least 6 months after the last dose of trial therapy.
- NOTE: Highly effective contraception is defined as methods with a failure rate <1% per year when used consistently and correctly, and include: copper intrauterine device (IUD); bilateral tubal ligation/occlusion or other documented surgical sterilization; vasectomized partner with documented azoospermia, provided this is the sole sexual partner; or true sexual abstinence, defined as complete abstinence from heterosexual intercourse, when this is the participant's usual and preferred lifestyle. Use of hormonal contraceptive methods (including combined oral contraceptives, progestin-only pills, injectables, implants, hormonal IUDs, patches, or vaginal rings) is not permitted during the study and for at least 6 months after the last dose of study treatment.
- Willingness and ability to comply with all study procedures, including scheduled visits, treatment plans, laboratory tests, and other protocol-specified requirements.
- Willingness and ability to sign and date written informed consent prior to initiation of any study-specific procedures.
- Disease Characteristics
- Breast and axillary imaging (mammogram, ultrasound, or MRI) must have been completed within 45 days prior to registration.
- Patients with abnormal axillary lymph nodes (identified clinically and/or radiographically) must undergo routine pathological confirmation via image-guided core biopsy or fine needle aspiration.
- Presence of:
- Measurable disease in the breast measuring at least 1cm with or without nodal involvement; or
- Clinical T0 disease with biopsy-proven regional lymph node involvement (cT0N1-2M0), consistent with an overall anatomic stage II-IIIB classification.
- For patients with clinical T0 disease confirmed by mammogram/US and MRI, nodal involvement must be documented by core needle biopsy or fine needle aspiration of an axillary or other regional lymph node demonstrating invasive breast carcinoma prior to initiation of neoadjuvant systemic therapy.
- Patients must not have undergone prior surgical excision of an invasive breast primary tumor that would account for the T0 designation (i.e., T0 must not be the result of complete prior excision of the primary breast lesion).
- Patients with multifocal or multicentric disease are allowed if the dominant tumor is confirmed ER and/or PR ≤10%, and HER2-negative.
- Patients with bilateral breast cancer are eligible if both tumors are HER2-negative.
- Staging scans (e.g., CT chest/abdomen/pelvis with a nuclear bone scan) must be performed to rule out metastatic disease under any of the following conditions:
- Two or more abnormal axillary lymph nodes on imaging, or b. Clinical suspicion of metastatic disease, or c. At the discretion of the treating physician.
- Clinical and Laboratory Requirements
- Peripheral neuropathy must be Grade ≤1 per CTCAE v5.0.
- Complete history and physical examination performed within 45 days prior to registration.
- Adequate hematologic and organ function as defined by the following:
- Hematologic i. Hemoglobin ≥9.0 g/dL (without transfusion or erythropoietin support within 14 days prior to testing) ii. Leukocytes ≥3,000/μL iii. Absolute neutrophil count (ANC) ≥1,500/μL iv. Platelet count ≥100,000/μL b. Hepatic i. AST (SGOT) and ALT (SGPT) ≤3 × ULN ii. For participants without a history of Gilbert's syndrome, total bilirubin ≤1.5 × upper limit of normal (ULN) iii. For participants with a history of Gilbert's syndrome, total bilirubin ≤5 × ULN c. Renal i. Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 mL/min/1.73 m² by Cockcroft-Gault formula.
- Note: Patients with creatinine clearance 30-50 mL/min may be enrolled at the discretion of the Principal Investigator, given that paclitaxel is primarily hepatically metabolized and carboplatin dosing can be adjusted to renal function.
- Cardiac function must be within acceptable limits, as follows: left ventricular ejection fraction (LVEF) ≥50% by
- Echocardiogram (ECHO), or b. Multi-gated acquisition (MUGA) scan.
- Participants with known human immunodeficiency virus (HIV)-infection must be on effective antiretroviral therapy (ART) at randomization and have an undetectable viral load test on the most recent test results obtained within six (6) months prior to randomization.
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within six (6) months prior to randomization, if indicated.
- NOTE: No testing for HBV is required unless mandated by local health authority.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have an undetectable HCV viral load test on the most recent test results obtained within six (6) months prior to randomization, if indicated.
- NOTE: No testing for HCV is required unless mandated by local health authority.
Who cannot join
- Participants meeting any of the following criteria will be excluded from the study:
- Pre-Screening Phase:
- 1. Presence of tumor-infiltrating lymphocytes (TILs) <30% based on central pathology review of hematoxylin and eosin (H\&E) stained slides.
- Screening and Treatment Phases:
- Disease-Related Exclusions
- Presence of N3, inflammatory, or metastatic (M1) breast cancer.
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- History of other malignancies within the past 3 years, with the exception of:
- Adequately treated non-melanoma skin cancer, or
- Cervical carcinoma in situ, or
- Other malignancies with a ≥3-year disease-free interval. Prior and Concurrent Therapy
- Prior systemic therapy, radiation therapy, or definitive surgery for current breast cancer.
- Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, or any other T-cell co-inhibitory or co-stimulatory agents.
- Use of investigational agents or devices within 28 days prior to registration
- Participant is planning to participate, currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Medical Conditions
- History of severe (Grade ≥3) allergic reactions or hypersensitivity to study drugs or their components.
- Uncontrolled diabetes mellitus or hypertension.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy (7-day clearance period for immunosuppressant therapy prior to starting study treatment, if applicable).
- History of solid organ transplant.
- Active autoimmune disease requiring systemic treatment within the past 1 year.
- Recent (within 12 weeks) or active non-infectious pneumonitis requiring corticosteroid therapy.
- Major surgical procedure or active/severe infection within 14 days prior to registration.
- Subject is a WOCBP who has had a positive pregnancy test within 24 hours prior to initiation of study treatment. Females will be determined to be not of child-bearing potential with a history of hysterectomy or with postmenopausal status of >12 months.
- Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 180 days after the last dose of trial treatment.
- History of hypersensitivity to compounds that are similar to carboplatin and paclitaxel.
- Has received major surgery and has not recovered adequately from the toxicity and/or complications before starting study treatment.
- Has a history of non-infectious pneumonitis that required high-dose steroids and/or has current pneumonitis.
- Has an active bacterial infection requiring systemic therapy.
- Known psychiatric or substance abuse disorders that would interfere with the requirements of the trial.
- Vaccination
- Administration of live vaccines within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza or COVID vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Medical University of South Carolina Hollings Cancer Center,
Charleston, South Carolina, 29425
HCC Clinical Trials Office, 843-792-9321, hcc-clinical-trials@musc.edu
- Not yet recruiting
SUNY Upstate Medical University
Syracuse, New York, 13210
Erinn Mcdowell, McDowelE@upstate.edu
About this study
Official title: NeoTILs: A Phase II Study of Biomarker-Guided De-escalation Using Anthracycline-Free Neoadjuvant Chemoimmunotherapy in Early-Stage Triple Negative Breast Cancer (TNBC) Patients With High Tumor-Infiltrating Lymphocytes (TILs)
This study tests a new treatment approach for people with early-stage triple negative breast cancer whose tumors have a high number of immune cells, called tumor-infiltrating lymphocytes or TILs, as seen by a pathologist on tissue review. A high TIL count is a sign the cancer may respond especially well to chemotherapy and immunotherapy together, meaning more toxic treatment may not be needed for everyone.
All patients with high TILs will receive 12 weeks of chemotherapy (carboplatin and paclitaxel) with the immunotherapy drug pembrolizumab before surgery, without anthracyclines, a class of chemotherapy drugs that is effective but carries risks of heart damage and, rarely, bone marrow disorders or leukemia. Patients with no cancer found at surgery continue on pembrolizumab alone. Those with residual cancer receive anthracycline-based chemotherapy plus pembrolizumab, closer to current standard treatment.
The goal is to personalize treatment, sparing anthracyclines for patients likely to do well without them while reserving stronger therapy for those who need it. The main measure of success is the pathologic complete response rate, with cancer-free survival and overall survival also assessed.
Read the detailed description
NeoTILs is a single-arm, single-institution phase II non-inferiority trial evaluating a 12-week neoadjuvant regimen of carboplatin, paclitaxel, and pembrolizumab (CPP) in patients with early-stage (anatomic Stage II to IIIB) triple negative breast cancer whose tumors show high tumor-infiltrating lymphocytes (TILs), defined as TILs of 30 percent or greater on a digitized hematoxylin and eosin slide from the diagnostic biopsy, assessed centrally. The trial tests whether the pathologic complete response (pCR) rate achieved with this anthracycline-free neoadjuvant regimen is not significantly inferior to the historical pCR rate of 65 percent reported with the KEYNOTE-522 regimen in a comparable TIL-enriched population.
Following pre-screening consent and confirmation of high TIL status, eligible patients are formally consented and enrolled. All patients receive 12 weeks of neoadjuvant CPP, with anthracycline omitted entirely from the neoadjuvant phase, followed by definitive surgery. Treatment after surgery is determined by pathologic response, making this a response-adapted design. Patients who achieve pCR continue pembrolizumab alone to complete a total of nine doses and never receive anthracycline chemotherapy. Patients with residual invasive disease in the breast or axillary lymph nodes receive adjuvant doxorubicin and cyclophosphamide together with continued pembrolizumab for four cycles, consistent with current standard of care, and also complete the planned nine total doses of pembrolizumab. Additional adjuvant therapy, including olaparib for patients with germline BRCA1 or BRCA2 mutations and capecitabine for residual disease, may be given at the treating physician's discretion.
The trial uses a group sequential design with a planned futility analysis at 50 percent information (n1 = 25) and a maximum sample size of 50 evaluable patients if the futility boundary is not crossed, out of an anticipated screening population of approximately 150 patients. Continuous safety monitoring begins with the sixth patient enrolled, with significant safety events defined as grade 3 or 4 adverse events or serious adverse events, or a surgical delay of more than 12 weeks, judged definitely or probably related to the neoadjuvant regimen.
The primary endpoint is pCR rate. Secondary endpoints include three-year event-free survival, three- and five-year overall survival, treatment-related toxicity, incidence of chemotherapy-induced peripheral neuropathy, and patient-reported quality of life measured with the EORTC QLQ-C30 and QLQ-CIPN20 at baseline, end of neoadjuvant therapy, and 6 and 12 months post-treatment. Exploratory endpoints include near-pCR rate (residual cancer burden 0 or 1), radiographic response, and correlation of baseline and on-treatment TIL levels, PD-L1 expression, and circulating tumor DNA dynamics with pathologic response and long-term survival outcomes. Patients are followed for a minimum of five years for event-free and overall survival.
- Being tested
- Carboplatin, Paclitaxcel, Pembrolizumab
- Keywords
- Triple Negative Breast Cancer, Neoadjuvant chemoimmunotherapy, Neoadjuvant treatment, TILs, TIL, anthracycline sparing, non-anthracycline based
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Target AUC 5 every 3 weeks for 12 weeks (depending on response) OR Target AUC 1.5 every week for 12 weeks (depending on response).
PaclitaxcelDrug
80 mg/m2 every week for 12 weeks.
PembrolizumabDrug
200 mg every 3 weeks for 4-6 cycles (depending on response).
| Study group | Role | What they receive |
|---|---|---|
| pCR for TNBC patients high TILs treated w/neoadjuvant CPP regimen not significantly inferior | Experimental | Patients will receive carboplatin, paclitaxel, pembrolizumab. Followed by surgery. After surgery, if pCR = pembro maintenance. If no pCR = adjuvant AC/Pembro Receives: Drug: Carboplatin; Drug: Paclitaxcel; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of pCR in breast and axilla
proportion of patients who experience a pathologic complete response (pCR) and report an exact binomial (Clopper-Pearson) 95% confidence interval (CI) to convey precision
Measured: 60 months
Secondary outcomes (4)
Event-free survival (EFS)
the time from the start of treatment to the first occurrence of any of the following events: disease progression during NAC, failure to undergo surgery due to progression or toxicity, local, regional or distant recurrence, or death from any cause.
Measured: 60 months
Overall survival
time from the start of treatment until death from any cause.
Measured: 60 months
Quality of life (QOL)
will be assessed using EORTC QLQ-C30 at baseline, at the conclusion of neoadjuvant chemotherapy (NAC) , and at 6 and 12 months post-NAC.
Measured: 12 months post surgery
Incidence and Severity of Adverse Events
Frequency and grade of adverse events per CTCAE v5.0.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2026
- Study start1 Jan 2027 (estimated)
- Primary completion22 Sep 2029 (estimated)
- Study completion29 May 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (56)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- State University of New York - Upstate Medical University
- Responsible party
- Principal investigator, Abirami Sivapiragasam, Medical University of South Carolina
- Investigators
- Abirami Sivapiragasam, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07743190
- Sponsor's protocol ID
- 104044
- Acronym
- NeoTILs
- Status last verified
- Oct 2026
- First submitted
- 29 Jul 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Loi, S., et al., Abstract LBO1-03: Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N). Cancer Research, 2024. 84(9_Supplement): p. LBO1-03-LBO1-03.
Yuan Y. Modelling the spatial heterogeneity and molecular correlates of lymphocytic infiltration in triple-negative breast cancer. J R Soc Interface. 2015 Feb 6;12(103):20141153. doi: 10.1098/rsif.2014.1153.
PubMed 25505134Maley CC, Koelble K, Natrajan R, Aktipis A, Yuan Y. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Res. 2015 Sep 22;17(1):131. doi: 10.1186/s13058-015-0638-4.
PubMed 26395345Zhang H, AbdulJabbar K, Moore DA, Akarca A, Enfield KSS, Jamal-Hanjani M, Raza SEA, Veeriah S, Salgado R, McGranahan N, Le Quesne J, Swanton C, Marafioti T, Yuan Y. Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma. Cancer Res. 2023 May 2;83(9):1410-1425. doi: 10.1158/0008-5472.CAN-22-2589.
PubMed 36853169AbdulJabbar K, Raza SEA, Rosenthal R, Jamal-Hanjani M, Veeriah S, Akarca A, Lund T, Moore DA, Salgado R, Al Bakir M, Zapata L, Hiley CT, Officer L, Sereno M, Smith CR, Loi S, Hackshaw A, Marafioti T, Quezada SA, McGranahan N, Le Quesne J; TRACERx Consortium; Swanton C, Yuan Y. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma. Nat Med. 2020 Jul;26(7):1054-1062. doi: 10.1038/s41591-020-0900-x. Epub 2020 May 27.
PubMed 32461698Schlam, I., et al., Artificial intelligence (AI) based spatial assessment of tumor-infiltrating lymphocytes (TIL) and pathologic complete response in early HER2+ breast cancer (BC): Secondary analysis of NSABP B-41. Journal of Clinical Oncology, 2025. 43(16_suppl): p. 551-551.
Loi, S., et al. Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N). in SABCS. 2023. San Antonio.
Gluz O, Nitz U, Kolberg-Liedtke C, Prat A, Christgen M, Kuemmel S, Mohammadian MP, Gebauer D, Kates R, Pare L, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Wuerstlein R, Graeser M, Pelz E, Jozwiak K, Zu Eulenburg C, Kreipe HH, Harbeck N; ADAPT TN investigators. De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial. Clin Cancer Res. 2022 Nov 14;28(22):4995-5003. doi: 10.1158/1078-0432.CCR-22-0482.
PubMed 35797219Sharma P, Stecklein SR, Yoder R, Staley JM, Schwensen K, O'Dea A, Nye L, Satelli D, Crane G, Madan R, O'Neil MF, Wagner J, Larson KE, Balanoff C, Kilgore L, Phadnis MA, Godwin AK, Salgado R, Khan QJ, O'Shaughnessy J. Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial. JAMA Oncol. 2024 Feb 1;10(2):227-235. doi: 10.1001/jamaoncol.2023.5033.
PubMed 37991778Sharma P, Kimler BF, O'Dea A, Nye L, Wang YY, Yoder R, Staley JM, Prochaska L, Wagner J, Amin AL, Larson K, Balanoff C, Elia M, Crane G, Madhusudhana S, Hoffmann M, Sheehan M, Rodriguez R, Finke K, Shah R, Satelli D, Shrestha A, Beck L, McKittrick R, Pluenneke R, Raja V, Beeki V, Corum L, Heldstab J, LaFaver S, Prager M, Phadnis M, Mudaranthakam DP, Jensen RA, Godwin AK, Salgado R, Mehta K, Khan Q. Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP). Clin Cancer Res. 2021 Feb 15;27(4):975-982. doi: 10.1158/1078-0432.CCR-20-3646. Epub 2020 Nov 18.
PubMed 33208340Hershman DL, Shao T. Anthracycline cardiotoxicity after breast cancer treatment. Oncology (Williston Park). 2009 Mar;23(3):227-34.
PubMed 19418823Mata Caballero R, Serrano Antolin JM, Jimenez Hernandez RM, Talavera Calle P, Curcio Ruigomez A, Del Castillo Arrojo S, Graupner Abad C, Cristobal Varela C, Alonso Martin JJ. Incidence of long-term cardiotoxicity and evolution of the systolic function in patients with breast cancer treated with anthracyclines. Cardiol J. 2022;29(2):228-234. doi: 10.5603/CJ.a2020.0062. Epub 2020 Apr 24.
PubMed 32329038Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kummel S, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Im SA, Untch M, Fasching PA, Mouret-Reynier MA, Foukakis T, Ferreira M, Cardoso F, Zhou X, Karantza V, Tryfonidis K, Aktan G, O'Shaughnessy J; KEYNOTE-522 Investigators. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024 Nov 28;391(21):1981-1991. doi: 10.1056/NEJMoa2409932. Epub 2024 Sep 15.
PubMed 39282906FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer [cited 2024 March 13]; Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer.
Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gomez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in Early Breast Cancer: The ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. doi: 10.1200/JCO.2016.71.4147. Epub 2017 Apr 11.
PubMed 28398846
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NeoTILs: A Phase II Study of Biomarker-Guided De-escalation Using Anthracycline-Free Neoadjuvant Chemoimmunotherapy in Early-Stage Triple Negative Breast Cancer (TNBC) Patients With High Tumor-Infiltrating Lymphocytes (TILs)
- ClinicalTrials.gov ID
- NCT07743190
- Acronym / sponsor ID
- NeoTILs / 104044
- Keywords
- Triple Negative Breast Cancer, Neoadjuvant chemoimmunotherapy, Neoadjuvant treatment, TILs, TIL, anthracycline sparing, non-anthracycline based
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- State University of New York - Upstate Medical University
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 22 Sep 2029 (estimated)
- Study completion
- 29 May 2034 (estimated)
- First posted
- 3 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study tests a new treatment approach for people with early-stage triple negative breast cancer whose tumors have a high number of immune cells, called tumor-infiltrating lymphocytes or TILs, as seen by a pathologist on tissue review. A high TIL count is a sign the cancer may respond especially well to chemotherapy and immunotherapy together, meaning more toxic treatment may not be needed for everyone.
All patients with high TILs will receive 12 weeks of chemotherapy (carboplatin and paclitaxel) with the immunotherapy drug pembrolizumab before surgery, without anthracyclines, a class of chemotherapy drugs that is effective but carries risks of heart damage and, rarely, bone marrow disorders or leukemia. Patients with no cancer found at surgery continue on pembrolizumab alone. Those with residual cancer receive anthracycline-based chemotherapy plus pembrolizumab, closer to current standard treatment.
The goal is to personalize treatment, sparing anthracyclines for patients likely to do well without them while reserving stronger therapy for those who need it. The main measure of success is the pathologic complete response rate, with cancer-free survival and overall survival also assessed.
Detailed description
NeoTILs is a single-arm, single-institution phase II non-inferiority trial evaluating a 12-week neoadjuvant regimen of carboplatin, paclitaxel, and pembrolizumab (CPP) in patients with early-stage (anatomic Stage II to IIIB) triple negative breast cancer whose tumors show high tumor-infiltrating lymphocytes (TILs), defined as TILs of 30 percent or greater on a digitized hematoxylin and eosin slide from the diagnostic biopsy, assessed centrally. The trial tests whether the pathologic complete response (pCR) rate achieved with this anthracycline-free neoadjuvant regimen is not significantly inferior to the historical pCR rate of 65 percent reported with the KEYNOTE-522 regimen in a comparable TIL-enriched population.
Following pre-screening consent and confirmation of high TIL status, eligible patients are formally consented and enrolled. All patients receive 12 weeks of neoadjuvant CPP, with anthracycline omitted entirely from the neoadjuvant phase, followed by definitive surgery. Treatment after surgery is determined by pathologic response, making this a response-adapted design. Patients who achieve pCR continue pembrolizumab alone to complete a total of nine doses and never receive anthracycline chemotherapy. Patients with residual invasive disease in the breast or axillary lymph nodes receive adjuvant doxorubicin and cyclophosphamide together with continued pembrolizumab for four cycles, consistent with current standard of care, and also complete the planned nine total doses of pembrolizumab. Additional adjuvant therapy, including olaparib for patients with germline BRCA1 or BRCA2 mutations and capecitabine for residual disease, may be given at the treating physician's discretion.
The trial uses a group sequential design with a planned futility analysis at 50 percent information (n1 = 25) and a maximum sample size of 50 evaluable patients if the futility boundary is not crossed, out of an anticipated screening population of approximately 150 patients. Continuous safety monitoring begins with the sixth patient enrolled, with significant safety events defined as grade 3 or 4 adverse events or serious adverse events, or a surgical delay of more than 12 weeks, judged definitely or probably related to the neoadjuvant regimen.
The primary endpoint is pCR rate. Secondary endpoints include three-year event-free survival, three- and five-year overall survival, treatment-related toxicity, incidence of chemotherapy-induced peripheral neuropathy, and patient-reported quality of life measured with the EORTC QLQ-C30 and QLQ-CIPN20 at baseline, end of neoadjuvant therapy, and 6 and 12 months post-treatment. Exploratory endpoints include near-pCR rate (residual cancer burden 0 or 1), radiographic response, and correlation of baseline and on-treatment TIL levels, PD-L1 expression, and circulating tumor DNA dynamics with pathologic response and long-term survival outcomes. Patients are followed for a minimum of five years for event-free and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pCR for TNBC patients high TILs treated w/neoadjuvant CPP regimen not significantly inferior | Experimental | Drug: Carboplatin, Drug: Paclitaxcel, Drug: PembrolizumabPatients will receive carboplatin, paclitaxel, pembrolizumab. Followed by surgery. After surgery, if pCR = pembro maintenance. If no pCR = adjuvant AC/Pembro |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Age ≥ 18 years at the time of informed consent.
- Ability to understand and willingness to sign a written informed consent document in accordance with institutional and federal guidelines.
- Histologically confirmed diagnosis of triple-negative breast cancer (TNBC) or hormone receptor-low invasive breast carcinoma, with clinical anatomic Stage II or Stage IIIA/B as defined by the AJCC 8th Edition Anatomic Breast Cancer Staging System.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- General Eligibility
Key exclusion criteria (31 listed)
- 1. Presence of tumor-infiltrating lymphocytes (TILs) <30% based on central pathology review of hematoxylin and eosin (H\&E) stained slides.
- Disease-Related Exclusions
- Presence of N3, inflammatory, or metastatic (M1) breast cancer.
- History of other malignancies within the past 3 years, with the exception of:
- Prior systemic therapy, radiation therapy, or definitive surgery for current breast cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinTarget AUC 5 every 3 weeks for 12 weeks (depending on response) OR Target AUC 1.5 every week for 12 weeks (depending on response). | Drug | pCR for TNBC patients high TILs treated w/neoadjuvant CPP regimen not significantly inferior |
| Paclitaxcel80 mg/m2 every week for 12 weeks. | Drug | pCR for TNBC patients high TILs treated w/neoadjuvant CPP regimen not significantly inferior |
| Pembrolizumab200 mg every 3 weeks for 4-6 cycles (depending on response). | Drug | pCR for TNBC patients high TILs treated w/neoadjuvant CPP regimen not significantly inferior |
Primary outcome
Rate of pCR in breast and axilla
Time frame: 60 months
proportion of patients who experience a pathologic complete response (pCR) and report an exact binomial (Clopper-Pearson) 95% confidence interval (CI) to convey precision
4 secondary outcomes
Event-free survival (EFS)
Time frame: 60 months
Overall survival
Time frame: 60 months
Quality of life (QOL)
Time frame: 12 months post surgery
Incidence and Severity of Adverse Events
Time frame: 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- BackgroundLoi, S., et al., Abstract LBO1-03: Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N). Cancer Research, 2024. 84(9_Supplement): p. LBO1-03-LBO1-03.
- Background: PubMed 25505134Yuan Y. Modelling the spatial heterogeneity and molecular correlates of lymphocytic infiltration in triple-negative breast cancer. J R Soc Interface. 2015 Feb 6;12(103):20141153. doi: 10.1098/rsif.2014.1153.
- Background: PubMed 26395345Maley CC, Koelble K, Natrajan R, Aktipis A, Yuan Y. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Res. 2015 Sep 22;17(1):131. doi: 10.1186/s13058-015-0638-4.
- Background: PubMed 36853169Zhang H, AbdulJabbar K, Moore DA, Akarca A, Enfield KSS, Jamal-Hanjani M, Raza SEA, Veeriah S, Salgado R, McGranahan N, Le Quesne J, Swanton C, Marafioti T, Yuan Y. Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma. Cancer Res. 2023 May 2;83(9):1410-1425. doi: 10.1158/0008-5472.CAN-22-2589.
- Background: PubMed 32461698AbdulJabbar K, Raza SEA, Rosenthal R, Jamal-Hanjani M, Veeriah S, Akarca A, Lund T, Moore DA, Salgado R, Al Bakir M, Zapata L, Hiley CT, Officer L, Sereno M, Smith CR, Loi S, Hackshaw A, Marafioti T, Quezada SA, McGranahan N, Le Quesne J; TRACERx Consortium; Swanton C, Yuan Y. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma. Nat Med. 2020 Jul;26(7):1054-1062. doi: 10.1038/s41591-020-0900-x. Epub 2020 May 27.
- BackgroundSchlam, I., et al., Artificial intelligence (AI) based spatial assessment of tumor-infiltrating lymphocytes (TIL) and pathologic complete response in early HER2+ breast cancer (BC): Secondary analysis of NSABP B-41. Journal of Clinical Oncology, 2025. 43(16_suppl): p. 551-551.
- BackgroundLoi, S., et al. Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N). in SABCS. 2023. San Antonio.
- Background: PubMed 35797219Gluz O, Nitz U, Kolberg-Liedtke C, Prat A, Christgen M, Kuemmel S, Mohammadian MP, Gebauer D, Kates R, Pare L, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Wuerstlein R, Graeser M, Pelz E, Jozwiak K, Zu Eulenburg C, Kreipe HH, Harbeck N; ADAPT TN investigators. De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial. Clin Cancer Res. 2022 Nov 14;28(22):4995-5003. doi: 10.1158/1078-0432.CCR-22-0482.
- Background: PubMed 37991778Sharma P, Stecklein SR, Yoder R, Staley JM, Schwensen K, O'Dea A, Nye L, Satelli D, Crane G, Madan R, O'Neil MF, Wagner J, Larson KE, Balanoff C, Kilgore L, Phadnis MA, Godwin AK, Salgado R, Khan QJ, O'Shaughnessy J. Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial. JAMA Oncol. 2024 Feb 1;10(2):227-235. doi: 10.1001/jamaoncol.2023.5033.
- Background: PubMed 33208340Sharma P, Kimler BF, O'Dea A, Nye L, Wang YY, Yoder R, Staley JM, Prochaska L, Wagner J, Amin AL, Larson K, Balanoff C, Elia M, Crane G, Madhusudhana S, Hoffmann M, Sheehan M, Rodriguez R, Finke K, Shah R, Satelli D, Shrestha A, Beck L, McKittrick R, Pluenneke R, Raja V, Beeki V, Corum L, Heldstab J, LaFaver S, Prager M, Phadnis M, Mudaranthakam DP, Jensen RA, Godwin AK, Salgado R, Mehta K, Khan Q. Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP). Clin Cancer Res. 2021 Feb 15;27(4):975-982. doi: 10.1158/1078-0432.CCR-20-3646. Epub 2020 Nov 18.
- Background: PubMed 19418823Hershman DL, Shao T. Anthracycline cardiotoxicity after breast cancer treatment. Oncology (Williston Park). 2009 Mar;23(3):227-34.
- Background: PubMed 32329038Mata Caballero R, Serrano Antolin JM, Jimenez Hernandez RM, Talavera Calle P, Curcio Ruigomez A, Del Castillo Arrojo S, Graupner Abad C, Cristobal Varela C, Alonso Martin JJ. Incidence of long-term cardiotoxicity and evolution of the systolic function in patients with breast cancer treated with anthracyclines. Cardiol J. 2022;29(2):228-234. doi: 10.5603/CJ.a2020.0062. Epub 2020 Apr 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Abirami Sivapiragasam, MD principal investigator
Medical University of South Carolina
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin, Paclitaxcel and Pembrolizumab in people with Triple Negative Breast Cancer (TNBC) and Elevated Tumor-Infiltrating Lymphocytes, run by Medical University of South Carolina at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 38 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact HCC Clinical Trials Office (843-792-9321, hcc-clinical-trials@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of pCR in breast and axilla (time frame: 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07743190, which also lists 56 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.