MRI-guided early surgery and reduced chemotherapy for stage II–III triple-negative breast cancer

NOGA: Neoadjuvant Treatment Optimization Via MRI-Guided De-Escalation in Stage II-III TNBC - A Phase 2 Study.

This trial will try using MRI to decide whether adults with stage II–III triple-negative breast cancer who are receiving a pembrolizumab-containing neoadjuvant regimen can have earlier surgery and less chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tel-Aviv Sourasky Medical Center (Government)
• Drugs / interventions: pembrolizumab, cyclophosphamide, doxorubicin, prednisone, chemotherapy, immunotherapy
• Locations: 2 sites (Tel Aviv and 1 other locations)
• Trial ID: NCT07327021 on ClinicalTrials.gov

What this trial studies

This is a phase 2 interventional protocol for patients eligible for the KEYNOTE-522 neoadjuvant regimen (paclitaxel, carboplatin, doxorubicin, cyclophosphamide plus pembrolizumab). Participants must have histologically confirmed triple-negative breast cancer (ER/PR <1%, HER2 negative), stage T2-3N0 or T1-3N1, no distant metastases on FDG-PET, and a visible tumor on contrast-enhanced breast MRI performed within 35 days prior to enrollment. MRI response will guide a de-escalation strategy that may include earlier surgery instead of completing the full planned neoadjuvant course. Nodal status is assessed by ultrasound with biopsy if suspicious, and standard clinical eligibility and performance status criteria apply.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed stage II–III triple-negative breast cancer who are eligible for the KEYNOTE-522 regimen, have a visible tumor on contrast-enhanced MRI, no distant metastases, and WHO performance status ≤2.

Not a fit: Patients with metastatic disease, hormone-receptor or HER2-positive tumors, tumors not visible on MRI, or those unable to undergo MRI are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the approach could allow some patients to avoid additional chemotherapy cycles and related toxicities by moving to earlier surgery based on MRI response.

How similar studies have performed: Adding pembrolizumab to neoadjuvant chemotherapy improved pCR and survival in KEYNOTE-522, but MRI-guided de-escalation strategies are relatively novel and not yet established.

Eligibility criteria

Inclusion Criteria:

* Patient is eligible per physician's discretion for the KEYNOTE-522 regimen (Neoadjuvant paclitaxel-carboplatin-doxorubicin-cyclophosphamide-pembrolizumab)
* Signed written informed consent
* Histologically confirmed primary infiltrating breast cancer with estrogen receptor expression \<1%, Progesterone receptor expression \<1%, and without overexpression and/or amplification of HER2 according to ASCO/CAP 2013 guideline (locally assessed)
* T2-3N0, T1-3N1 disease according to TNM-staging (8th edition, AJCC).
* Nodal status must be examined by ultrasound and fine-needle aspiration or core biopsy in case of suspicious lymph nodes.
* No evidence of distant metastases (Stage IV disease) on FDG-PET performed within 35 days of enrollment.
* Age ≥18
* WHO performance status ≤ 2
* Visible breast tumor on contrast enhanced MRI (no minimal longest diameter required)
* MRI breast must be performed within 35 days prior to registration
* Patients with a history of autoimmune disease are eligible for the study per treating physician's discretion.
* Laboratory requirements - within 21 days prior to enrollment:

  * Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l)
  * Adequate hepatic function (ALT, AST and bilirubin ≤2.5 times upper limit of normal)
  * Subjects with Gilbert's syndrome may have a total bilirubin ≥2.5 × the ULN range, if no evidence of biliary obstruction exists;
  * Adequate renal function: creatinine clearance \>50 ml/min estimated using the Cockcroft-Gault equation, or based on a 24-hour urine collection measurement
  * LVEF ≥50% measured by echocardiography
* Women of childbearing potential and men must agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods (failure rate of \<1% per year,) during treatment and for at least 6 months after the last dose of pembrolizumab. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative β-HCG serum or urine pregnancy test result.

Exclusion Criteria:

* Concurrent breastfeeding
* Concurrent contralateral or ipsilateral non-TNBC second primary infiltrating breast cancer. Contralateral or ipsilateral TNBC second primary infiltrating breast cancer or DCIS is allowed.
* Concurrent anti-cancer treatment or another investigational drug
* Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Patients who have a history of a second malignancy are eligible, provided the malignancy has been adequately treated, there is no ongoing treatment for the second malignancy, and overall principal investigator (PI) approval is obtained.
* Has undergone excisional biopsy of the primary tumor, and/or axillary lymph node dissection prior to study treatment.
* 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 within 7 days prior to the first dose of study intervention.
* History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Where this trial is running

Tel Aviv and 1 other locations

• Tel Aviv Sourasky Medical Center — Tel Aviv, Israel (Recruiting)
• Sheba Medical Center — Tel Litwinsky, Israel (Recruiting)

Study contacts

• Study coordinator: Tal Sella, MD

Conditions TNBC, Triple Negative Breast Cancer; Early Breast Cancer; TNBC; KEYNOTE-522; MRI