160+ HER2-Positive Breast Cancer Clinical Trials Recruiting Now (August 2026)

Last updated: August 30, 2026

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Why HER2 Status Defines a Different Trial Pathway

Roughly 15–20% of breast cancers are HER2-positive (ERBB2-amplified), and that one biomarker opens an entirely separate treatment pathway — one of the most drug-rich in all of oncology, with more than a dozen approved HER2-targeted agents and hundreds of active trials. HER2 status is assessed independently of hormone-receptor (ER/PR) status, so a tumor can be HER2-positive and either hormone-receptor-positive or triple-for-HER2 (HR-negative, HER2-positive). If you're HER2-positive, the trials worth looking at are different from those for HER2-negative or triple-negative disease.

HER2 testing required: IHC 3+, or IHC 2+ with positive ISH/FISH for gene amplification. Almost all HER2-positive trials require this confirmation. If your tumor is IHC 1+ or IHC 2+/ISH-negative, you're "HER2-low" — a distinct and now separately-treatable category (see below).

How HER2 Status is Confirmed

HER2 testing in breast cancer follows the ASCO/CAP guideline algorithm. The pathologist starts with immunohistochemistry (IHC) on a tumor biopsy and assigns one of four scores based on how strongly HER2 protein stains on the cell membrane:

IHC 0 — no staining, or faint/incomplete staining in ≤10% of cells. HER2-zero.
IHC 1+ — faint, incomplete membrane staining in >10% of cells. HER2-low — eligible for HER2-low trials and for trastuzumab deruxtecan.
IHC 2+ — weak-to-moderate complete membrane staining in >10% of cells. Equivocal — reflexively confirmed with ISH/FISH. IHC 2+/ISH-positive = HER2-positive; IHC 2+/ISH-negative = HER2-low.
IHC 3+ — strong complete membrane staining in >10% of cells. HER2-positive — eligible for the full HER2-targeted toolkit.

For IHC 2+ tumors, an in situ hybridization (ISH/FISH) test counts copies of the HER2 gene. A HER2:CEP17 ratio ≥ 2.0 (or average HER2 copy number ≥ 6) confirms amplification — equivalent to HER2-positive for trial eligibility.

Re-testing matters. HER2 status can differ between the primary tumor and a metastasis, and can change after treatment. If your initial biopsy was HER2-negative and you've since progressed, a fresh biopsy of a metastatic lesion is worth discussing with your oncologist — some trials specifically allow re-testing for eligibility, and a switch to HER2-low or HER2-positive can open entirely new options.

Already-Approved HER2-Targeted Therapies (2026 Standard of Care)

Outside a clinical trial, here's what your oncologist would currently offer for HER2-positive breast cancer. Trial decisions usually compare against (or build on) these standards:

First-line metastatic (CLEOPATRA "THP"): docetaxel + trastuzumab + pertuzumab, median overall survival ~57 months — the long-standing 1L standard.
Second line — trastuzumab deruxtecan (T-DXd, ENHERTU): in DESTINY-Breast03, T-DXd extended median progression-free survival to 28.8 vs 6.8 months versus T-DM1, making it the clear 2L standard.
Third line and beyond: tucatinib + trastuzumab + capecitabine (HER2CLIMB — notable for brain-metastasis activity); trastuzumab emtansine / T-DM1 (EMILIA); margetuximab + chemo (SOPHIA); neratinib + capecitabine (NALA).
HER2-low metastatic: trastuzumab deruxtecan is approved based on DESTINY-Breast04 (median OS 23.4 vs 16.8 months vs chemotherapy), with DESTINY-Breast06 extending benefit to earlier and HER2-ultralow disease.
Early-stage / (neo)adjuvant: neoadjuvant trastuzumab + pertuzumab + chemotherapy; adjuvant T-DM1 for residual disease after neoadjuvant therapy (KATHERINE); adjuvant neratinib after trastuzumab (ExteNET) in higher-risk HR-positive disease.

Approval status varies by country. The above reflects FDA + EMA labels as of August 2026. Local availability and reimbursement differ.

Current Trial Landscape (August 2026)

Active research areas:

Next-generation HER2 ADCs (BL-M07D1, SHR-A1811/trastuzumab rezetecan, disitamab vedotin, ARX788) testing whether different payloads or linkers improve on T-DXd — including after T-DXd progression
HER2 bispecific antibodies (zanidatamab, KN026) moving into first-line, neoadjuvant, and adjuvant settings
Brain-metastasis-directed regimens — tucatinib and HER2 ADC combinations with radiotherapy and intrathecal therapy for CNS and leptomeningeal disease
First-line challengers to the trastuzumab + pertuzumab standard (new ADCs and antibodies head-to-head against THP)
HER2-low expansion into its own dedicated ADC pipeline
Vaccines and immunotherapy combinations in early-stage and locally advanced disease

Standard of care (2026): 1L metastatic — docetaxel + trastuzumab + pertuzumab (CLEOPATRA). 2L — trastuzumab deruxtecan (DESTINY-Breast03). 3L+ — tucatinib + trastuzumab + capecitabine (HER2CLIMB, brain-active), T-DM1, margetuximab, neratinib. HER2-low — T-DXd (DESTINY-Breast04).

Recruiting Trials by Treatment Setting

First-Line Metastatic HER2+

Testing whether new HER2 ADCs, antibodies, and bispecifics improve on the trastuzumab + pertuzumab + taxane standard:

NCT07377643 — IBI354 (HER2 ADC) with or without pertuzumab vs taxane + trastuzumab + pertuzumab in HER2-positive breast cancer (head-to-head against the THP standard)
NCT05838066 — KN026 (HER2 bispecific antibody) + HB1801 in first-line HER2-positive recurrent or metastatic breast cancer
NCT06641544 — Different combination regimens of inetetamab (anti-HER2 monoclonal antibody) in first-line HER2-positive metastatic breast cancer
NCT06254690 — Pyrotinib (HER2 TKI) dosing regimen in HER2-positive advanced first-line breast cancer

Second-Line and Beyond — HER2 ADCs & Bispecifics

After progression on trastuzumab-based therapy — the most active area, including agents studied after T-DXd:

NCT06435429 — Zanidatamab (HER2 bispecific) vs trastuzumab, each in combination with chemotherapy, in metastatic HER2-positive breast cancer
NCT05461768 — BL-M07D1 (next-generation HER2 ADC) in locally advanced or metastatic HER2-positive breast cancer and other solid tumors

Brain Metastases & Leptomeningeal Disease

HER2-positive breast cancer has a high rate of CNS spread. These trials specifically address brain and leptomeningeal metastases — a setting where tucatinib and T-DXd have proven intracranial activity:

NCT06016387 — Tucatinib + trastuzumab + capecitabine with brain and/or spinal radiotherapy in HER2-positive breast cancer with CNS/leptomeningeal disease
NCT05800275 — Capecitabine + tucatinib + intrathecal trastuzumab for HER2-positive breast cancer with leptomeningeal metastasis
NCT05769010 — SHR-A1811 (HER2 ADC) in HER2-expressing advanced breast cancer with brain metastases
NCT07503717 — SURVEY-CNS: a randomization-feasibility study in HER2-positive metastatic breast cancer with CNS involvement

Early-Stage — Neoadjuvant & Adjuvant

Curative-intent trials testing de-escalation (chemo-free HER2 blockade) and new agents before or after surgery:

NCT06162559 — Neoadjuvant trastuzumab + pertuzumab + tucatinib without chemotherapy in HER2-positive breast cancer (chemo-free de-escalation)
NCT07102381 — Neoadjuvant zanidatamab (HER2 bispecific) + chemotherapy in HER2-positive breast cancer
NCT07441460 — KN026 + HB1801 as adjuvant therapy for resectable HER2-positive breast cancer (Phase 3)

HER2-Low (IHC 1+ or IHC 2+/ISH-Negative)

HER2-low is now its own treatment category with a dedicated next-generation ADC pipeline. If your IHC is 1+ or 2+/ISH-negative, these are recruiting:

NCT06224673 — ARX788 (HER2 ADC) in HER2-low locally advanced unresectable or metastatic breast cancer
NCT07203729 — Trastuzumab rezetecan (SHR-A1811) in HER2-low unresectable/metastatic breast cancer
NCT05831878 — RC48-ADC (disitamab vedotin) in HER2-low advanced breast cancer
NCT06832202 — HLX22 + trastuzumab deruxtecan in HER2-low, hormone-receptor-positive breast cancer

Vaccines & Immunotherapy Combinations

Earlier-stage and prevention-oriented approaches training the immune system against HER2:

NCT06949410 — HER2 vaccine for locally advanced HER2-positive breast cancer
NCT04144023 — H2NVAC vaccine before surgery for HER2-expressing ductal carcinoma in situ (DCIS)

Showing selected notable HER2-positive-specific trials. View all recruiting HER2-positive breast cancer trials on ClinicalTrials.gov (~160 HER2-positive-specific recruiting in August 2026). Every trial listed above was verified as recruiting in ClinTrialFinder's corpus as of August 30, 2026.

Frequently Asked Questions

What does HER2-positive mean in breast cancer?

HER2-positive breast cancer means the tumor overexpresses HER2 (ERBB2) protein or has amplification of the HER2 gene, defined as IHC 3+, or IHC 2+ with a positive ISH/FISH test. Roughly 15–20% of breast cancers are HER2-positive. HER2 status is required for trastuzumab-based, HER2 ADC, and HER2 bispecific trials, and is assessed separately from hormone-receptor (ER/PR) status.

What is the standard treatment for HER2-positive metastatic breast cancer in 2026?

First line is typically docetaxel + trastuzumab + pertuzumab (the CLEOPATRA "THP" regimen, median OS ~57 months). Second line is trastuzumab deruxtecan (T-DXd), which in DESTINY-Breast03 extended median PFS to 28.8 vs 6.8 months versus T-DM1. Third line and beyond includes tucatinib + trastuzumab + capecitabine (HER2CLIMB, with brain-metastasis activity), T-DM1, margetuximab, and neratinib + capecitabine.

What clinical trials are available for HER2-positive breast cancer?

About 160 recruiting interventional trials specifically for HER2-positive breast cancer are active in August 2026, spanning next-generation HER2 ADCs (BL-M07D1, SHR-A1811/trastuzumab rezetecan, disitamab vedotin, ARX788), HER2 bispecific antibodies (zanidatamab, KN026), tucatinib-based brain-metastasis regimens, first-line challengers to the trastuzumab + pertuzumab standard, HER2-low expansion cohorts, and neoadjuvant/adjuvant studies.

I have brain metastases from HER2-positive breast cancer. Am I eligible for trials?

Yes, often. HER2-positive breast cancer has a high rate of brain metastasis, and several regimens have documented intracranial activity: tucatinib + trastuzumab + capecitabine (HER2CLIMB) and trastuzumab deruxtecan both work in the brain. Dedicated CNS trials are recruiting, including combinations with brain/spinal radiotherapy and intrathecal trastuzumab for leptomeningeal disease. Treated/stable brain mets are frequently allowed; untreated or actively symptomatic mets are still excluded from some protocols.

What about HER2-low breast cancer?

HER2-low (IHC 1+, or IHC 2+ with a negative ISH test) is now a distinct treatment category. Trastuzumab deruxtecan is FDA-approved for HER2-low metastatic breast cancer based on DESTINY-Breast04 (median OS 23.4 vs 16.8 months vs chemotherapy). Multiple trials are recruiting HER2-low patients for next-generation ADCs (ARX788, SHR-A1811, disitamab vedotin/RC48) and combinations. HER2-low eligibility differs from HER2-positive, so testing precision matters.

Can I join a HER2 ADC trial after prior trastuzumab or T-DXd?

Usually yes. Most second-line-and-beyond HER2 ADC and bispecific trials require prior trastuzumab-based therapy, and many now enroll patients who have already progressed on trastuzumab deruxtecan (post-T-DXd is an active area of study). First-line trials testing new agents against the trastuzumab + pertuzumab standard typically exclude prior anti-HER2 therapy for metastatic disease but allow it in the adjuvant/neoadjuvant setting if completed 6–12 months earlier. Always check the specific trial's washout and prior-therapy requirements.

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