Scope. ClinicalTrials.gov listed roughly 1,400 actively recruiting TNBC-relevant studies as of early 2026 (search query: "Triple Negative Breast Cancer", status: recruiting). The categories below are a navigational starting map, not an enumeration.
Why trials matter in TNBC specifically
Three things make TNBC unusually trial-dependent compared with hormone-receptor-positive or HER2-positive breast cancer:
- Fewer standard-of-care targeted options. Outside the BRCA-mutated subset (PARP inhibitors) and the PD-L1-positive subset (immune checkpoint inhibitors), targeted choices are limited. Many patients exhaust standard options earlier than HR+ or HER2+ patients do.
- Chemosensitivity buys time but not cure. Even patients who achieve pathologic complete response on neoadjuvant therapy have substantial recurrence risk in the first 3–5 years. Trials testing escalation, de-escalation, or alternative regimens directly address this.
- The molecular heterogeneity (BL1, BL2, IM, MES, MSL, LAR; Burstein’s BLIA / BLIS / MES / LAR) is real but not yet routinely actioned in clinical practice. Most subtype-stratified treatment hypotheses are only testable inside trials.
The patient-layer counterpart to this page (treatment options) makes a stronger version of this point for patients: ask about trials at every decision point.
Major active trial categories
Roughly grouped, and linked to ClinicalTrials.gov filtered views where the search syntax allows useful filtering:
1. Antibody-drug conjugates beyond sacituzumab and trastuzumab deruxtecan
Trials of next-generation Trop-2 ADCs (datopotamab deruxtecan), B7-H4 ADCs, HER3-DXd, novel HER2-low strategies (including patients with HER2-ultra-low or HER2 0 by current scoring), and ADC combinations with checkpoint inhibitors or PARP inhibitors. ClinicalTrials.gov — recruiting ADC trials in TNBC →
2. Immunotherapy beyond pembrolizumab
Novel checkpoint targets (TIGIT, LAG-3), bispecifics, adoptive cell therapy (TIL therapy, CAR-T), oncolytic viruses, and rational combinations with chemotherapy, ADCs, PARP inhibitors, and radiation. Earlier-line use of immunotherapy in PD-L1-negative or low-CPS disease is an active area. ClinicalTrials.gov — recruiting immunotherapy trials in TNBC →
3. PARP inhibitors and the homologous-recombination-deficiency space
Extension of PARP-inhibitor benefit beyond germline BRCA1/2 — testing HRD-score-positive but BRCA-wildtype tumors, combinations with immunotherapy, and POLQ inhibitors for HR-proficient tumors. ClinicalTrials.gov — recruiting PARP trials in TNBC →
4. Subtype-stratified targeted therapy
Androgen-receptor antagonists (enzalutamide, bicalutamide, darolutamide) for the luminal-androgen-receptor (LAR) subtype; AKT and PI3K inhibitors for PI3K-pathway-altered TNBC; CDK4/6 inhibitors in specific contexts. These are smaller, biomarker-stratified trials and the eligibility criteria matter.
5. Neoadjuvant intensification and de-escalation
Trials testing whether the KEYNOTE-522 backbone can be intensified for patients at especially high recurrence risk, or de-escalated (shorter duration, fewer cycles, omission of anthracyclines) for patients with favorable response signals. ctDNA-guided adaptive trials are a notable subgroup. The I-SPY platform continues to be the dominant infrastructure here.
6. Adjuvant escalation for residual disease
Following the OlympiA precedent (adjuvant olaparib for BRCA-mutated high-risk residual disease), multiple trials test adjuvant ADCs, immunotherapy continuation, and combinations in patients with residual cancer burden > 0 after neoadjuvant therapy.
7. Brain-metastasis-specific trials
Given the disproportionate CNS metastasis pattern in TNBC, trials of CNS-penetrant ADCs, novel small molecules with intracranial activity, and combinations with whole-brain or stereotactic radiation are an important and historically under-served subspace.
8. Biomarker-discovery and translational studies
Window-of-opportunity trials, baseline-and-on-treatment biopsy studies, ctDNA dynamics, single-cell and spatial-transcriptomic correlative work. Often run alongside therapeutic trials.
Trial design types currently active
The trial landscape has shifted in the last decade toward designs that share infrastructure and biomarker selection across arms:
- Adaptive platform trials. I-SPY 2 / 2.2 is the dominant neoadjuvant platform for high-risk early breast cancer including TNBC, with Bayesian adaptive randomization across ten-plus simultaneously-tested experimental arms. Multiple TNBC-relevant drug approvals have come out of I-SPY.
- Basket and umbrella trials. Basket trials enroll patients across tumor types selected by a shared biomarker (e.g., HRD-positive solid tumors). Umbrella trials enroll patients within a single tumor type stratified into biomarker-defined sub-arms.
- Randomized phase 2 / 3 sequential designs. The pivotal-trial workhorse; KEYNOTE-522, KEYNOTE-355, ASCENT, and DESTINY-Breast04 are all in this family.
- Early-phase first-in-human and dose-escalation trials. Increasingly important as the ADC and bispecific pipelines mature; these are often the only path to novel-mechanism options once standard therapy is exhausted.
Where trials are running
Three overlapping infrastructures account for most TNBC trial activity in the US:
- NCI-designated comprehensive cancer centers (Dana-Farber, MD Anderson, MSKCC, Yale, UCSF, Vanderbilt, Duke, Hopkins, and many others). Highest density of early-phase and biomarker-stratified trials.
- NCI cooperative groups (NRG Oncology, Alliance, SWOG, ECOG-ACRIN) run large multicenter trials that enroll broadly across academic and community sites.
- Industry-sponsored multicenter trials run at a mix of academic and community sites; ClinicalTrials.gov is the primary discovery surface.
Outside the US, the European Organisation for Research and Treatment of Cancer (EORTC), the German Breast Group (GBG), and the Japanese Breast Cancer Study Group (JBCSG) are the dominant cooperative-group infrastructures.
Assessing trial fit at the patient level
Standard considerations when discussing a trial with a patient:
- Setting. Early-stage neoadjuvant / adjuvant / metastatic first-line / metastatic later-line — each trial is open to one of these. Most trial protocols are very specific.
- Biomarker eligibility. PD-L1 CPS threshold, germline BRCA status, HRD score, HER2-low status, AR expression — each can be a gate.
- Prior therapy history. Some trials exclude patients with prior anthracycline, prior immunotherapy, prior ADC of the same drug class, etc.
- Organ function and performance status. Standard inclusion / exclusion criteria.
- Logistical fit. Travel time to the trial site, frequency of in-person visits, supportive-care availability, insurance coordination (most trials cover the experimental drug and trial-specific procedures; routine care continues to be billed to insurance).
- Goals of treatment. A phase 1 dose-escalation trial in a heavily-pre-treated metastatic patient has a different goal than a phase 3 adjuvant trial in someone with curative intent.
Cooperative group and trial-network resources
- NCI Clinical Trials Search — the NCI’s patient-and-clinician-friendly front-end on ClinicalTrials.gov, with TNBC-specific filtering.
- ClinicalTrials.gov — the authoritative registry; required listing for most US-regulated trials.
- Triple Negative Breast Cancer Foundation — patient-facing trial-matching support and educational resources.
- Metavivor — metastatic-breast-cancer-focused trial advocacy.
- The I-SPY 2 / 2.2 platform homepage and the NCI MATCH / ComboMATCH precision-medicine trial pages list active arms across multiple cancer types.
What this page deliberately does not do
- We do not mirror ClinicalTrials.gov. They update in real time and have far more resources for trial-registry maintenance than this project ever will. Linking out is correct.
- We do not endorse specific trials, sponsors, or sites. The categories above are descriptive of the landscape, not a recommendation.
- We do not offer trial-matching for individual patients. The patient-advocacy organizations linked above do this professionally and far better than we could; a treating oncologist’s research nurse is the most effective first step.
- We do not interpret unpublished trial results. Synthesis pages on this site cover trials only after they are published in peer-reviewed form; press releases and conference abstracts inform our future drafting but are not cited as evidence.
Last reviewed: 2026-05-18. Trial-landscape categories shift as new mechanism classes mature; this page is re-reviewed quarterly. Specific trial counts and links go out of date faster than the page is revised — treat them as orientation, not as a registry.