Trastuzumab Deruxtecan (T-DXd / Enhertu) Clinical Trials (May 2026): 145 Recruiting Interventional Studies

Last updated: May 25, 2026

About Trastuzumab Deruxtecan

Active Research Directions in 2026

• Earlier-line and adjuvant breast cancer — multiple Phase 3 trials are testing T-DXd in (neo)adjuvant settings (DESTINY-Breast05 in residual disease post-neoadjuvant; DESTINY-Breast11 in high-risk HER2-positive; secondary adjuvant studies) and at the 1L decision point now that DESTINY-Breast09 has set the new combination standard.
• HER2-ultralow expansion — the January 2025 approval based on DESTINY-Breast06 opened a major new eligible population. Confirmatory and combination studies continue.
• Head-to-head against next-generation HER2 ADCs — SHR-A1811 (Jiangsu Hengrui's anti-HER2 ADC) is now in head-to-head Phase 3 versus T-DXd in HER2-positive early breast cancer (NCT06126640). Zanidatamab (Jazz/Zymeworks, HER2 × HER2 bispecific antibody) is also in head-to-head Phase 3 in metastatic HER2-positive breast cancer (NCT06435429).
• Endometrial cancer Phase 3 — DESTINY-Endometrial01 (NCT06989112) and another Phase 3 vs standard chemo (NCT07022483) are establishing T-DXd in HER2-expressing endometrial cancer, a new major indication push.
• Brain metastases / CNS — T-DXd has shown meaningful intracranial activity in HER2-positive breast cancer brain metastases (DESTINY-Breast12). 9 active recruiting trials include CNS-focused studies and leptomeningeal disease.
• Combination with immunotherapy — multiple Phase 3 trials combine T-DXd with PD-(L)1 inhibitors (pembrolizumab, durvalumab) or anti-TIGIT (rilvegostomig) in breast, gastric/GEJ, biliary, and pan-tumor settings. The Phase 3 T-DXd + rilvegostomig vs SoC in advanced biliary tract cancer (NCT06467357) is particularly notable.
• 1L gastric Phase 3 — T-DXd-based combinations are moving into the 1L gastric/GEJ setting (NCT06764875 with rilvegostomig; NCT06731478 with chemo + pembro + trastuzumab).
• Pediatric and adolescent expansion — trials in adolescent HER2-positive solid tumors are now opening.
• Long-term access programs — NCT06174987 provides continued access and long-term safety assessment in patients who have previously received T-DXd, given the breadth of approved indications.

Recruiting Trials by Indication

Breast Cancer (84 recruiting — the dominant indication)

Spans 1L combination, HER2-low / ultralow / pan-HER2-expression, adjuvant / perioperative, brain metastases, head-to-head studies, and novel partner drugs:

• NCT04784715 — DESTINY-Breast09 (Phase 3) — T-DXd + pertuzumab vs THP in 1L HER2-positive metastatic breast cancer. FDA-approved December 15, 2025 based on this trial. ASCO 2026 Rapid Oral Abstract #1021.
• NCT06435429 — Phase 3 zanidatamab vs T-DXd in metastatic HER2-positive breast cancer (head-to-head against the leading HER2 bispecific antibody).
• NCT06126640 — Phase 3 SHR-A1811 (Jiangsu Hengrui anti-HER2 ADC) vs T-DXd in HER2-positive early breast cancer (head-to-head against a next-gen HER2 ADC).
• NCT05950945 — Phase 3 T-DXd in patients who have hormone receptor-positive HER2 something breast cancer.
• NCT06643585 — Phase 3 randomized secondary adjuvant treatment intervention in breast cancer.
• Additional Phase 1/2 combinations with CDK4/6 inhibitors, endocrine therapy, PI3K/AKT pathway agents, and novel checkpoint partners.

HER2-Positive Pan-Tumor / Tumor-Agnostic (32 recruiting)

Building on the April 2024 DESTINY-PanTumor02 approval for HER2-positive (IHC 3+) advanced solid tumors regardless of primary site:

• NCT06174987 — long-term access and safety assessment program for patients with HER2-expressing advanced cancers across tumor types.
• Multiple basket Phase 2 studies in rare HER2-expressing solid tumors (salivary gland, bile duct, ampullary, etc.).

Gastric and Gastroesophageal Junction Cancer (20 recruiting)

Approved indication (2L+ HER2-positive metastatic) since 2021; current trials push T-DXd into 1L combinations and explore novel partner drugs:

• NCT06764875 — Phase 3 rilvegostomig (PD-1 × TIGIT bispecific) + fluoropyrimidine + T-DXd in HER2-positive gastric / GEJ.
• NCT06731478 — Phase 3 T-DXd + chemotherapy + pembrolizumab + trastuzumab in gastric / GEJ.

HER2-Mutant NSCLC (18 recruiting)

Approved indication since April 2024 (DESTINY-Lung02); active expansion into 1L and combination settings:

• NCT06899126 — Phase 3 T-DXd + pembrolizumab + platinum chemotherapy in NSCLC.

Ovarian Cancer (12 recruiting)

• NCT06819007 — Phase 3 T-DXd + bevacizumab vs bevacizumab alone in ovarian cancer.

Endometrial Cancer (8 recruiting — emerging major indication)

• NCT06989112 — DESTINY-Endometrial01 (Phase 3) in HER2-expressing endometrial cancer.
• NCT07022483 — Phase 3 T-DXd vs standard-of-care chemotherapy in endometrial cancer.

Biliary Tract Cancer / Cholangiocarcinoma (4 recruiting)

• NCT06467357 — Phase 3 T-DXd + rilvegostomig vs SoC in advanced biliary tract cancer.

CNS / Brain Metastases (9 recruiting)

T-DXd has demonstrated meaningful intracranial activity in HER2-positive breast cancer brain metastases (DESTINY-Breast12). Active trials specifically address CNS metastases and leptomeningeal disease.

Other Indications

• Colorectal cancer: 9 trials — HER2-amplified mCRC combinations.
• Pancreatic cancer: 8 trials — HER2-expressing pancreatic adenocarcinoma combinations.
• Bladder / urothelial: 6 trials — HER2-expressing urothelial cancer. Note NCT06524544 compares pembrolizumab + sacituzumab govitecan vs T-DXd in HER2-expressing locally advanced urothelial.
• Head & neck SCC, sarcoma, salivary gland, cervical: 3-5 trials each, smaller earlier-phase combinations.

Showing pivotal Phase 3 anchors and indication-cluster summaries. The full set of 145 recruiting interventional studies (plus 47 not-yet-recruiting in setup) includes additional investigator-initiated combinations and basket studies not listed above. View the latest on ClinicalTrials.gov.

Patient Selection and HER2 Biomarker Testing

HER2-status testing is the gate for T-DXd eligibility, but the relevant HER2 thresholds vary by indication:

• HER2-positive (IHC 3+, or IHC 2+ with FISH amplification): the traditional HER2-positive population. Approved indications include breast (1L + 2L+ metastatic), gastric/GEJ, NSCLC (with HER2 mutation), and pan-tumor.
• HER2-low (IHC 1+, or IHC 2+ without FISH amplification): approved in breast cancer since May 2022 (DESTINY-Breast04). About half of all metastatic breast cancers fall in this range — the approval roughly doubled the eligible population.
• HER2-ultralow (IHC 0 with weak / incomplete membrane staining in >10% of tumor cells): approved in breast cancer since January 2025 (DESTINY-Breast06). Further expanded the eligible population beyond traditional HER2-low.
• HER2-mutant (NSCLC): activating mutations in the HER2 (ERBB2) gene, typically detected on tumor next-generation sequencing or liquid biopsy. Distinct from HER2 amplification.
• Re-biopsy on progression matters: HER2 status changes in 10–20% of patients between primary tumor and metastasis. A fresh biopsy can convert a previously "HER2-negative" patient to HER2-low / HER2-positive eligible, opening T-DXd as a new option.

Side Effects and Practical Considerations

• ⚠️ Interstitial lung disease (ILD) / pneumonitis — the most important safety concern with T-DXd. Rare but potentially serious lung inflammation. Any new respiratory symptoms (cough, shortness of breath, fever) require immediate evaluation, treatment interruption, and (if confirmed) corticosteroid management. Patients with prior ILD, active pneumonia, or significant pulmonary impairment require careful pre-treatment evaluation.
• Nausea and vomiting — very common; standard practice is prophylactic antiemetic regimens (typically a 5-HT3 antagonist + dexamethasone, often plus NK1 antagonist for delayed nausea).
• Fatigue — common throughout treatment.
• Alopecia — hair loss is common.
• Low blood counts — neutropenia, anemia, thrombocytopenia. Routine CBC monitoring; dose modifications per protocol if Grade 3+.
• Cardiac monitoring — LVEF assessed at baseline and periodically. The trastuzumab antibody backbone historically had cardiac concerns; T-DXd has generally shown a manageable cardiac profile in practice.
• Decreased appetite and constipation — common; managed supportively.
• Combination-specific toxicities — T-DXd + pertuzumab (the new 1L breast standard) adds diarrhea risk from pertuzumab. T-DXd + chemotherapy combinations add the toxicities of the partner regimen. T-DXd + immunotherapy combinations add immune-related event risk.

Frequently Asked Questions

This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.