Improving immune response in triple negative breast cancer patients

Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients: the TONIC-2 Trial

Phase 2 Interventional The Netherlands Cancer Institute · NCT04159818

This study is testing a combination of treatments to see if they can boost the immune response in patients with metastatic triple negative breast cancer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment52 (estimated)
Ages18 Years and up
SexAll
SponsorThe Netherlands Cancer Institute Academic / other
Drugs / interventionschemotherapy, radiation, doxorubicin, prednisone, nivolumab
Locations1 site (Amsterdam)
Trial IDNCT04159818 on ClinicalTrials.gov

What this trial studies

This phase II trial aims to evaluate immune induction strategies to enhance the effectiveness of immune checkpoint blockade in patients with metastatic triple negative breast cancer. The study will involve administering nivolumab, cisplatin, and low-dose doxorubicin to patients, with a focus on assessing their immune response through paired biopsies. The trial follows a Simon's two-stage design, where initial cohorts of 13 patients will be evaluated for treatment response before expanding to a total of 34 if responses are observed.

Who should consider this trial

Good fit: Ideal candidates include adults with metastatic or incurable locally advanced triple negative breast cancer who have had limited prior chemotherapy and accessible metastatic lesions for biopsy.

Not a fit: Patients with symptomatic brain metastases or those who have previously experienced anthracycline-related cardiac toxicity may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with metastatic triple negative breast cancer.

How similar studies have performed: Other studies have shown promise in using immune checkpoint inhibitors in similar patient populations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Metastatic or incurable locally advanced triple negative breast cancer (ER \< 10%, HER2 IHC 0,1+ or 2+ with no amplification)
* Metastatic lesion accessible for histological biopsy
* 18 years or older
* Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease. Treatment with low-dose doxorubicin in the palliative setting is not allowed.
* WHO performance status of 0 or 1
* Measurable or evaluable disease according to RECIST 1.1
* Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year
* Subjects with brain metastases are eligible if these are not symptomatic and free of progression of at least 4 weeks
* A maximum dosage of 360 mg/m2 of anthracyclines and no previous anthracycline-related cardiac toxicity. In case of radiation in the cardiac area, hypertension, diabetes mellitus or hypercholesterolemia, the left ventricular ejection fraction must be 50% or higher.
* Adequate bone marrow, kidney and liver function

Exclusion Criteria:

* uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
* known history of leptomeningeal disease localization
* history of having received other anticancer therapies within 2 weeks of start of the study drug
* history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (\>10 mgl daily prednisone equivalents) or chronic infections.
* prior treatment with immune checkpoint inhibitors.
* active other cancer
* history of uncontrolled serious medical or psychiatric illness
* current pregnancy or breastfeeding

Where this trial is running

Amsterdam

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Metastatic Breast CancerTriple negativeMetastatic disease
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.