1,848 Breast Cancer Clinical Trials Recruiting Now (May 2026): T-DXd, HER2+, HER2-low, TNBC, HR+, ADC

Last updated: May 25, 2026

🔔 Pre-ASCO 2026 (May 29 – June 2) update: The December 15, 2025 FDA approval of trastuzumab deruxtecan (T-DXd) + pertuzumab as first-line therapy for HER2-positive metastatic breast cancer (based on DESTINY-Breast09, NCT04784715) is the first new 1L HER2+ MBC standard in a decade. The DESTINY-Breast09 Rapid Oral Abstract (Plenary candidate) at ASCO 2026 is widely anticipated. New Phase 3 entrants this month: patritumab deruxtecan (HER3-DXd) in breast cancer (NCT07060807) and Dato-DXd extending to HER2-zero (NCT07205822).

Current Clinical Trial Landscape

Active research areas in 2026:

Antibody-drug conjugates — ADCs (155+ trials): T-DXd, sacituzumab govitecan, sacituzumab tirumotecan (MK-2870), datopotamab deruxtecan (Dato-DXd, now extending to HER2-zero), patritumab deruxtecan (HER3-DXd) — new Phase 3 entrant, SHR-A1811, bispecific ADCs
CDK4/6 inhibitors (~160 trials): next-generation agents, new combinations with oral SERDs (palazestrant + ribociclib), adjuvant expansion, post-CDK4/6i strategies
Checkpoint immunotherapy (~146 trials): pembrolizumab in TNBC, PD-1/VEGF bispecifics, de-escalation studies
PIK3CA/AKT pathway inhibitors (~43 trials): inavolisib, capivasertib, gedatolisib, RLY-2608 (mutant-selective)
PARP inhibitors (~54 trials): olaparib, talazoparib, saruparib (next-gen PARP1-selective) for BRCA-mutated tumors
Oral SERDs (next-gen endocrine): camizestrant, palazestrant, D-0502 — replacing fulvestrant injections
HER2 bispecifics: zanidatamab head-to-head vs trastuzumab (with pertuzumab and chemo) — NCT06435429

Standard of care by subtype (updated for the Dec 2025 1L HER2+ approval): HR+/HER2-: Endocrine therapy + CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib) for metastatic; adjuvant endocrine therapy ± abemaciclib for high-risk early-stage. HER2+: T-DXd + pertuzumab is the new first-line metastatic standard (FDA-approved Dec 15, 2025 per DESTINY-Breast09); trastuzumab + pertuzumab + chemo remains an alternative; T-DM1 and chemo regimens for subsequent lines. TNBC: Pembrolizumab + chemotherapy (neoadjuvant/adjuvant for early-stage); sacituzumab govitecan or T-DXd for metastatic. HER2-low (IHC 1+ or 2+/ISH-) and HER2-ultralow (IHC 0 with membrane staining): T-DXd is approved per DESTINY-Breast04 / DESTINY-Breast06. BRCA-mutated: Olaparib or talazoparib for HER2- metastatic; olaparib adjuvant for high-risk HER2- early-stage.

Key Biomarkers for Trial Eligibility

Breast cancer treatment is driven by biomarkers. Knowing your status determines which trials you're eligible for:

Hormone receptor (ER/PR) status — ER+ and/or PR+ (~70% of breast cancers). Determines eligibility for endocrine therapy trials, CDK4/6 inhibitor combinations, and oral SERD trials.
HER2 status — HER2-positive (~15-20%), HER2-low (IHC 1+ or IHC 2+/ISH-negative, ~50%), or HER2-zero (IHC 0). HER2-low is now a distinct treatment category with T-DXd approved. HER2 ADC trials require specific IHC/FISH testing.
BRCA1/2 germline mutation — present in ~5-10% overall (higher in TNBC). Eligible for PARP inhibitors (olaparib, talazoparib, saruparib), platinum-based chemotherapy, and combination trials.
PIK3CA mutation — present in ~40% of HR+/HER2- tumors. Eligible for PI3K inhibitors (inavolisib, alpelisib), AKT inhibitors (capivasertib), and PI3K/mTOR inhibitors (gedatolisib).
PD-L1 expression (CPS) — determines eligibility for pembrolizumab in TNBC. CPS ≥10 is the standard cutoff for metastatic TNBC immunotherapy.
Ki-67 proliferation index — high Ki-67 may qualify for more intensive treatment or specific trial arms. Used in some risk stratification systems (e.g., Oncotype DX).
Tumor mutational burden (TMB) — TMB-high (≥10 mut/Mb) eligible for pembrolizumab regardless of subtype.

Know your HER2, ER/PR, and BRCA status? Get matched to breast cancer trials in minutes.

Find Matching Trials

Trials by Subtype

HR+/HER2- (Hormone Receptor Positive)

The most common subtype (~70%). Standard treatment includes endocrine therapy + CDK4/6 inhibitors. Key areas of innovation:

After CDK4/6i progression:
- NCT04862663 - CAPItello-292: Capivasertib + CDK4/6i + Fulvestrant (Phase 3)
- NCT05861830 - DAWNA-FES: Dalpiciclib + Endocrine Therapy after CDK4/6i failure (Phase 3)
- NCT06081959 - SKB264 (sacituzumab analog ADC) for HR+/HER2- (Phase 3)
- NCT06312176 - Sacituzumab Tirumotecan (MK-2870) + Pembrolizumab vs TPC (Phase 3)
PIK3CA-mutated:
- NCT06790693 - Inavolisib + CDK4/6i + Letrozole vs Placebo (Phase 3, first-line)
- NCT06982521 - RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant (Phase 3)
- NCT06757634 - Gedatolisib (PI3K/mTOR) as first-line treatment (Phase 3)
Next-gen SERDs / oral endocrine (now combining with CDK4/6i in 1L):
- NCT07085767 - Palazestrant + Ribociclib as first-line treatment for ER+/HER2- advanced breast cancer (Phase 3, new oral SERD + CDK4/6i combination in 1L)
- NCT06016738 - Palazestrant (OP-1250) vs SOC for ER+/HER2- (Phase 3)
- NCT05774951 - Camizestrant in ER+/HER2- early breast cancer (Phase 3)
- NCT06954961 - D-0502 for ER+/HER2- advanced breast cancer (Phase 3)
Adjuvant CDK4/6i expansion:
- NCT06341621 - Chemo omission with extended adjuvant abemaciclib, 1-3 positive nodes (Phase 3)
- NCT07190443 - AURA: Adjuvant abemaciclib for locoregional recurrence (Phase 3)
- NCT05827081 - Ribociclib + ET in early breast cancer (Phase 3b)
BRCA-mutated HR+:
- NCT06380751 - Saruparib (AZD5305) + Camizestrant vs CDK4/6i + ET (Phase 3)

HER2-Positive

~325 recruiting trials. The Dec 15, 2025 FDA approval of T-DXd + pertuzumab as first-line metastatic therapy (DESTINY-Breast09) has reshaped this setting. Active research focuses on next-gen ADCs, biosimilar comparators, de-escalation, and PIK3CA-mutated combinations:

First-line metastatic (post-Dec 2025 1L approval):
- NCT04784715 - DESTINY-Breast09: T-DXd ± pertuzumab vs taxane + trastuzumab + pertuzumab in 1L HER2+ MBC (Phase 3; basis of the Dec 2025 approval; ASCO 2026 Rapid Oral)
- NCT06435429 - Zanidatamab + pertuzumab + chemo vs trastuzumab + pertuzumab + chemo, 1L HER2+ MBC (Phase 3 head-to-head)
Neoadjuvant (before surgery):
- NCT06891833 - BL-M07D1 (HER2 ADC) ± Pertuzumab vs Taxane+THP (Phase 2/3)
- NCT04547907 - Nab-PHP vs TCbHP in HER2+ early breast cancer (Phase 3)
- NCT05883852 - EC-THP vs TCbHP in HER2+ node-positive (Phase 3)
- NCT07393425 - SHR-A1811 (HER2 ADC) + Pertuzumab neoadjuvant (Phase 2)
Metastatic / Advanced (later-line ADC comparators):
- NCT06846437 - JSKN003 vs T-DM1 for HER2+ advanced (Phase 3)
- NCT07008976 - TQB2102 vs T-DM1 for HER2+ advanced (Phase 3)
- NCT07294508 - HLX22 + HLX87 for HER2+ recurrent/metastatic (Phase 2/3)
- NCT05894239 - Inavolisib + Phesgo for PIK3CA-mutated HER2+ (Phase 3)
De-escalation:
- NCT06876714 - ShortStop-HER2: 12 vs 6 months HER2-targeted therapy after pCR (Phase 3)
- NCT06992882 - Oral chemo + trastuzumab vs paclitaxel + trastuzumab, node-negative (Phase 3)

Triple-Negative Breast Cancer (TNBC)

306 recruiting trials. Immunotherapy + chemotherapy is now standard in early TNBC. Active frontiers include ADCs and de-escalation:

First-line metastatic:
- NCT06926868 - Izalontamab Brengitecan (ADC) vs Chemo, first-line mTNBC (Phase 2/3)
- NCT06419621 - PM8002 (PD-L1/VEGF bispecific) + Nab-Paclitaxel, first-line (Phase 3)
- NCT06767527 - AK112 (PD-1/VEGF bispecific) + Nab-Paclitaxel, first-line (Phase 3)
- NCT07173751 - ROSETTA: Pumitamig in TNBC (Phase 3)
Pretreated / later-line:
- NCT06841354 - Sacituzumab Tirumotecan (MK-2870) ± Pembrolizumab in TNBC (Phase 3)
- NCT06279364 - SKB264 vs Chemo in recurrent/metastatic TNBC (Phase 3)
- NCT07111832 - SHR-A1811 in TNBC (Phase 3)
Neoadjuvant / early-stage:
- NCT06081244 - ADAPT-TN-III: SG vs SG+Pembrolizumab in low-risk early TNBC (Phase 3)
- NCT06606730 - Personalizing pembrolizumab use based on response (Phase 3)
- NCT05999149 - Camrelizumab + Chemo ± Famitinib neoadjuvant (Phase 3)
- NCT03150576 - Platinum + PARP inhibitor neoadjuvant for TNBC/gBRCA (Phase 2/3)
Post-neoadjuvant (non-pCR):
- NCT06393374 - Sacituzumab Tirumotecan + Pembrolizumab vs TPC in non-pCR TNBC (Phase 3)
- NCT06533384 - PARPi or Capecitabine + PD-1 inhibitor adjuvant in high-risk TNBC (Phase 3)

HER2-Low and HER2-Zero

~54 HER2-low recruiting trials. HER2-low = IHC 1+ or IHC 2+/ISH-negative; T-DXd is FDA-approved for HER2-low metastatic per DESTINY-Breast04 and HER2-ultralow (IHC 0 with membrane staining) per DESTINY-Breast06. New Dato-DXd trials are now extending into HER2-zero (IHC 0 without membrane staining):

NCT06486883 - T-DXd vs CDK4/6i-based ET as first-line in HR+/HER2-low (Phase 2)
NCT07071337 - SKB264 vs Chemo in HR+/HER2-low advanced (Phase 3)
NCT05950945 - T-DXd in HR-negative and HR-positive HER2-low/ultralow breast cancer (Phase 3 pan-HR)
NCT07205822 - Dato-DXd in HR+, HER2 IHC 0 (HER2-zero) inoperable/metastatic breast cancer (Phase 3, expanding TROP2 ADC into a previously-excluded subset)
NCT06103864 - Dato-DXd ± Durvalumab vs investigator's choice chemo (Phase 3)

HER3-Targeted (Pan-Subtype)

Patritumab deruxtecan (HER3-DXd) has entered Phase 3 in breast cancer as a new ADC class beyond HER2/TROP2 — HER3 is overexpressed across multiple breast cancer subtypes:

NCT07060807 - MK-1022-016: Patritumab Deruxtecan (HER3-DXd) in breast cancer (Phase 3, new Phase 3 entrant May 2026)

Novel Approaches

Next-gen ADCs: Sacituzumab tirumotecan (MK-2870), SKB264, izalontamab brengitecan, SHR-A1811, BL-M07D1 — improving on first-gen ADCs with new payloads and targets
HER3 ADC (new Phase 3 class): Patritumab deruxtecan (HER3-DXd) entering Phase 3 in breast cancer (NCT07060807, MK-1022-016)
Bispecific antibodies: PD-1/VEGF bispecifics (PM8002, AK112 / ivonescimab), HER2 bispecifics (zanidatamab head-to-head vs trastuzumab in 1L HER2+ MBC, HLX22+HLX87) — ~30 recruiting trials
Next-gen PARP inhibitors: Saruparib (AZD5305) with improved selectivity for PARP1, combined with novel endocrine agents (camizestrant)
Oral SERDs in 1L combinations: Palazestrant + ribociclib (1L Phase 3), camizestrant in early-stage, D-0502 — replacing fulvestrant injections and now pairing with CDK4/6i in first-line
Radiopharmaceuticals: NCT05870579 - [177Lu]Lu-NeoB + Ribociclib + Fulvestrant for GRPR+ ER+/HER2- (Phase 1b)

Showing selected notable trials. View all 1,848 recruiting interventional trials on ClinicalTrials.gov.

Frequently Asked Questions

How do I find breast cancer clinical trials for my subtype?

Enter your breast cancer details into ClinTrialFinder — including HER2 status (positive, low, or zero), hormone receptor status (ER/PR), BRCA mutations, PIK3CA status, PD-L1 expression, and prior treatments. The AI matches you with trials based on your specific profile in minutes. No login required.

What breast cancer trials are currently recruiting?

There are 1,848 recruiting interventional trials for breast cancer in May 2026, following the December 15, 2025 FDA approval of trastuzumab deruxtecan (T-DXd) + pertuzumab as 1L HER2+ metastatic therapy (DESTINY-Breast09). Active trials cover ADCs (T-DXd, datopotamab deruxtecan including new HER2-zero trials, sacituzumab govitecan, sacituzumab tirumotecan / MK-2870, patritumab deruxtecan / HER3-DXd, SHR-A1811, zanidatamab head-to-head vs trastuzumab), CDK4/6 inhibitors and oral SERD + CDK4/6i combinations (palazestrant + ribociclib 1L Phase 3), checkpoint immunotherapy, PARP inhibitors (saruparib for BRCA-mutated), PI3K/AKT pathway inhibitors (inavolisib, capivasertib, RLY-2608), oral SERDs, and PD-1/VEGF bispecific antibodies.

What is HER2-low breast cancer and how does it affect trial options?

HER2-low is a classification for breast cancers with IHC 1+ or IHC 2+/ISH-negative HER2 expression — about 50% of all breast cancers. Trastuzumab deruxtecan (T-DXd) is FDA-approved for HER2-low metastatic breast cancer based on the DESTINY-Breast04 trial, with eligibility extended to HER2-ultralow (IHC 0 with membrane staining) per DESTINY-Breast06. New Dato-DXd (datopotamab deruxtecan) Phase 3 trials are now also targeting HER2-zero (IHC 0 without membrane staining; NCT07205822). Ask your pathologist to confirm your exact HER2 IHC score and whether membrane staining is present, and consider re-biopsy at progression — HER2 expression can change between primary and metastatic samples.

What options are there after CDK4/6 inhibitor progression in HR+ breast cancer?

After progressing on CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), options include: PI3K/AKT pathway inhibitors (capivasertib, inavolisib for PIK3CA-mutated), ADCs (T-DXd, sacituzumab govitecan), oral SERDs (camizestrant, palazestrant), and next-generation PARP inhibitors (saruparib for BRCA-mutated). Many Phase 3 trials are specifically recruiting post-CDK4/6i patients.

Find Breast Cancer Trials Matched to Your Situation

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