marked.bio

HER2 ADC · ADC

trastuzumab deruxtecan

53 active trials across 11 of our biomarkers, targeting HER2. 6 active approvals for a biomarker on marked.bio.

Also known as T-DXd, DS-8201a, DS-8201, Enhertu.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
trastuzumab deruxtecan
FDA, 2022
unresectable or metastatic, activating HER2 mutation, after prior systemic therapy FDA accelerated approval 11/08/2022 (5.4 mg/kg). Source
EU (EMA), 2023
advanced, activating HER2 (ERBB2) mutation, needing systemic therapy after platinum chemotherapy with or without immunotherapy EU approval 23/10/2023 (company announcement). Source
Enhertu 		HER2 (ERBB2) activating mutation NSCLC Approved 2022 accelerated Approved 2023

In the US approval report

DESTINY-Lung02 single-arm, 52 patients
Response 58% (43-71)Lasting 8.7 months

Trial details and side effects
Patients
HER2-mutant NSCLC after systemic therapy (NCT04644237)
Most common side effects
nausea, fatigue, constipation, decreased appetite, vomiting, alopecia, low blood counts, raised liver enzymes
Notes
FDA approval as reported by ASCO Post (2022). Randomised dose-optimisation trial; figures are for the approved 5.4 mg/kg arm. Interstitial lung disease is a boxed warning.
Source
US approval report

In the EU approval report

DESTINY-Lung02 single-arm
Response 49% (39-59)Lasting 16.8 months

Trial details and side effects
Patients
HER2-mutant NSCLC after systemic therapy (NCT04644237)
Most common side effects
nausea, fatigue, constipation, decreased appetite, vomiting, alopecia, low blood counts, raised liver enzymes
Notes
Later DESTINY-Lung02 analysis at 5.4 mg/kg, as reported by the company at EU approval. Side effects from the US approval.
Source
EU approval report
trastuzumab deruxtecan
FDA, 2022
unresectable or metastatic HER2-low (IHC 1+ or 2+/ISH-), after chemotherapy Label: HER2-low (IHC 1+ or 2+/ISH-) after prior chemotherapy in the metastatic setting or recurrence within 6 months of adjuvant chemotherapy. Year confirmed: FDA approval announced 05/08/2022. Source
FDA, 2025
unresectable or metastatic HR-positive, HER2-low or HER2-ultralow, after >=1 endocrine therapy FDA approval 27/01/2025; label: HR-positive HER2-low or HER2-ultralow, progressed on >=1 endocrine therapy in the metastatic setting. Source
EU (EMA), 2023
unresectable or metastatic HER2-low, after chemotherapy II/0022, EC decision 23/01/2023. Enhertu's EU MA as a whole has been conditional since 18/01/2021; approval_type reflects the MA. Source
EU (EMA), 2025
unresectable or metastatic HR-positive, HER2-low or HER2-ultralow, after >=1 endocrine therapy in the metastatic setting and not suitable for endocrine therapy as next line II/0048, EC decision 31/03/2025. EU adds 'not considered suitable for endocrine therapy as the next line'. Enhertu MA conditional. Source
Enhertu 		HER2-low / ultralow (IHC 1+ or 2+/ISH-) breast Approved 2022 Approved 2023 conditional

In the FDA approval summary

DESTINY-Breast04 vs physician's choice chemotherapy, 373 vs 184 patients
PFS 9.9 months vs 5.1 months, HR 0.50 (0.40-0.63)OS 23.4 months vs 16.8 months, HR 0.64 (0.49-0.84)

Trial details and side effects
Patients
HER2-low metastatic breast cancer after chemotherapy (NCT03734029)
Most common side effects
nausea, fatigue, alopecia, vomiting, anaemia, constipation, decreased appetite
Notes
Boxed warning for interstitial lung disease and embryo-fetal toxicity. HR-positive cohort: PFS 10.1 vs 5.4 months, HR 0.51.
Source
FDA approval summary

In the EU product information

DESTINY-Breast04 vs physician's choice chemotherapy, 373 vs 184 patients
PFS 9.9 months vs 5.1 months, HR 0.50 (0.40-0.63)Response 52% vs 16%OS 23.4 months vs 16.8 months, HR 0.64 (0.49-0.84)

Trial details and side effects
Patients
HER2-low metastatic breast cancer after chemotherapy (NCT03734029)
Most common side effects
nausea, fatigue, alopecia, vomiting, anaemia, constipation, decreased appetite
Notes
EU SmPC section 5.1 (DESTINY-Breast04, all patients; HR-positive cohort 331 vs 163, PFS HR 0.51). Side effects from the US label.
Source
EU product information

In the EU product information

DESTINY-Breast06 vs physician's choice chemotherapy, 436 vs 430 patients
PFS 13.2 months vs 8.1 months, HR 0.64 (0.54-0.76)Response 57% vs 31%OS 28.9 months vs 27.4 months, HR 0.81 (0.66-1.01), interim

Trial details and side effects
Patients
HR-positive HER2-low or HER2-ultralow metastatic breast cancer after endocrine therapy, no prior chemotherapy for metastatic disease (NCT04494425)
Most common side effects
nausea 70%, fatigue 53%, alopecia 48%, diarrhoea 34%, vomiting 34%, constipation 32%, decreased appetite 26%, low white cells 86%, interstitial lung disease 11% (434 patients)
Notes
EU SmPC section 5.1 (DESTINY-Breast06, HER2-low and HER2-ultralow, March 2024 cut). Response not formally tested. Side effects from the US label. Side effects: Enhertu US prescribing information (DESTINY-Breast06, 5.4 mg/kg).
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
HER2-low / ultralow (IHC 1+ or 2+/ISH-) 40 46 Phase 3
HER2 (ERBB2) activating mutation 9 13 Phase 3
KRAS G12C 3 3 Phase 1/2
Claudin 18.2 expression 2 2 Phase 2
EGFR exon 19 deletion / L858R 2 2 Phase 1/2
BRCA1/2 mutation 1 1 Phase 1/2
EGFR exon 20 insertion 1 1 Phase 2
FGFR3 alteration (mutation or fusion) 1 1 Phase 1
IDH1/2 mutation 1 1 Phase 1/2
KRAS G12D 1 1 Phase 1/2
MSI-H / dMMR 1 1 Phase 2

Sponsors

Industry sponsors leading active biomarker-selected trials of trastuzumab deruxtecan.

  1. AstraZeneca 9
  2. Daiichi Sankyo 5
  3. Convalife 1
  4. Enliven Therapeutics 1
  5. Eli Lilly 1
  6. Jiangsu Hengrui 1
  7. Baili-Bio / SystImmune 1
  8. Henlius 1

Trials

53 of 62 trials shown

  1. Premedication With Dexamethasone for Preventing Interstitial Lung Disease in Patients With Breast Cancer Treated With Trastuzumab Deruxtecan

    Not yet recruiting Phase 3 Mario Negri Institute for Pharmacological Research Started 2026Primary completion 2030-12 NCT07828054

    dexamethasoneantiemetic premedicationtrastuzumab deruxtecan FDA EU

    HR-negative with expression of HER2-low ≤ 2 lines of chemotherapy in advanced disease

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, Interstitial Lung Disease (ILD)

  2. Megestrol Acetate for Fatigue Management in T-DXd Treated Breast Cancer

    Recruiting Phase 3 Sun Yat-sen University Started 2026Primary completion 2029-04 NCT07543536

    trastuzumab deruxtecan FDA EU

    HER2-positive (IHC 3+ or IHC 2+ with FISH positive), HER2-low (IHC 1+ or IHC 2+ with FISH negative), or HER2-ultralow (IHC 0 with ≤10% weak incomplete …

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced/Metastatic Breast Cancer, HER2+, Low, or Ultralow Advanced/Metastatic Breast Cancer

  3. A Randomized Secondary Adjuvant Treatment Intervention Study Comparing Trastuzumab-Deruxtecan to SOC Therapy in eBC Patients With Molecular Relapse

    Recruiting Phase 3 Prof. Wolfgang Janni Started 2025Primary completion 2032-04 NCT06643585

    trastuzumab deruxtecan FDA EU

    HER2-low defined as an immunohistochemistry (IHC) score of 1+ or an IHC score of 2+ with a mandato…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer

  4. Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer

    Recruiting Phase 3 Daiichi Sankyo Started 2023Primary completion 2027-10 NCT05950945

    trastuzumab deruxtecan FDA EUtrastuzumab

    In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer

  5. A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

    Active, not recruiting Phase 3 AstraZeneca Started 2021Primary completion 2026-06 NCT05048797

    trastuzumab deruxtecan FDA EUcisplatincarboplatinpembrolizumabpemetrexed

    Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA

    HER2 (ERBB2) activating mutationLocally Advanced or Metastatic Non-Small Cell Lung Cancer

  6. Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

    Active, not recruiting Phase 3 AstraZeneca Started 2020Primary completion 2024-03 NCT04494425

    trastuzumab deruxtecan FDA EUcapecitabinepaclitaxelnab-paclitaxel

    3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result establishe…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced or Metastatic Breast Cancer

  7. Testing the Combination of Anti-Cancer Drugs, Selumetinib and DS-8201a (Trastuzumab Deruxtecan), for Advanced Pancreatic Ductal Adenocarcinoma

    Recruiting Phase 1/2 National Cancer Institute (NCI) Starts 2027Primary completion 2028-09 NCT07619521

    selumetinibtrastuzumab deruxtecan

    Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2 immunohistochemistry (IHC) po…

    KRAS G12CKRAS G12DAdvanced Pancreatic Ductal Adenocarcinoma, Metastatic Pancreatic Ductal Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8

  8. Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation

    Recruiting Phase 1/2 National Cancer Institute (NCI) Started 2026Primary completion 2027-06 NCT07012031

    sotorasib FDA EUtrastuzumab deruxtecan

    …must have histologically or cytologically documented locally advanced or metastatic KRAS\^G12C-mutant NSCLC that has previously been treated with a KRAS\^G12C inhibitor AND an immune c…

    KRAS G12CLocally Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8

  9. Study of Trastuzumab Deruxtecan (T-DXd) in Combination With a RAGE Inhibitor in Patients With T-DXd-Resistant HER2-Positive or HER2-Low Metastatic Breast Cancer

    Not yet recruiting Phase 1/2 The Methodist Hospital Research Institute Started 2026Primary completion 2028-12 NCT07785856

    Azeliragontrastuzumab deruxtecan FDA EU

    Histologically confirmed HER2-positive or HER2-low or ultra low metastatic breast cancer.

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)T-dxd Resistant HER2-Positive, HER2 Low Metastatic Breast Cancer

  10. Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer

    Not yet recruiting Phase 2 UNICANCER Started 2026Primary completion 2029-10 NCT07151586

    sacituzumab govitecantrastuzumab deruxtecan FDA EU

    HER2-low breast cancer, defined as either immunohistochemistry (IHC) 2+ / in situ hybridization (I…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Triple Negative Breast Neoplasms, Neoplasm Metastasis, HER 2 Low-expressing Breast Cancer

  11. A Study of Patritumab Deruxtecan (HER3-DXd) in Combination With Trastuzumab Deruxtecan (T-DXd) in Participants With HR-Positive, HER2-Low or HER2-Ultralow Unresectable or Metastatic Breast Cancer

    Recruiting Phase 1/2 Daiichi Sankyo Started 2026Primary completion 2031-01 NCT07701941

    patritumab deruxtecantrastuzumab deruxtecan FDA EU

    Assessed as HER2-low (defined as Immunohistochemistry (IHC)2+/In-situ hybridization (ISH)- or IHC1+) or HER2-u…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Hormone Receptor Positive, HER2-low or HER2-ultralow, Unresectable or Metastatic Breast Cancer

  12. A Trial of Trastuzumab Rezetecan in Unresectable Locally Recurrent/Metastatic Breast Cancer

    Recruiting Phase 2 Jiangsu Hengrui Started 2026Primary completion 2028-06 NCT07497386

    trastuzumab rezetecantrastuzumab deruxtecan FDA EU

    …Treatment of Unresectable Locally Recurrent/Metastatic Breast Cancer With HR-Positive and HER2-Low Expression

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Unresectable Locally Recurrent Breast Cancer, Unresectable Locally Metastatic Breast Cancer

  13. Sequencing SG vs. T-DXd in HER2-Low/TROP2-High Metastatic Breast Cancer

    Not yet recruiting Phase 2 Fudan University Started 2026Primary completion 2027-06 NCT07368543

    sacituzumab govitecantrastuzumab deruxtecan FDA EU

    …etastatic breast cancer that is:HER2 IHC 1+ triple-negative breast cancer, or HR-positive/HER2-ultralow or HER2 IHC 1+ breast cancer.

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Metastatic Breast Cancer

  14. Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer

    Not yet recruiting Phase 2 Washington University School of Medicine Started 2026Primary completion 2030-10 NCT07619365

    trastuzumab deruxtecan FDA EULovastatin

    Histologically or cytologically confirmed HER2 low (IHC 1+ or 2+ with negative in-situ hybridization) or ultralow (IHC 0 with incomplete/fai…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer

  15. Trastuzumab Deruxtecan Plus ivonescImab for Hormone Receptor-positive HER2 Negative Advanced Breast Cancer Study

    Recruiting Phase 2 Fudan University Started 2026Primary completion 2027-12 NCT07647016

    trastuzumab deruxtecan FDA EUivonescimab

    …y confirmed Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2 (HER2)-low or HER2-ultralow breast cancer, with evidence of locally recurrent or metastatic disease …

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer

  16. A Study Comparing BL-M07D1 With DS-8201 in Patients With HR-Positive, HER2-Low Expressing Recurrent/Metastatic Breast Cancer

    Recruiting Phase 2 Baili-Bio / SystImmune Started 2026Primary completion 2028-12 NCT07678957

    BL-M07D1trastuzumab deruxtecan FDA EU

    Locally recurrent or metastatic breast cancer that is hormone receptor (HR)-positive and HER2-low expressing；

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer

  17. A Study of Trastuzumab Deruxtecan (T-DXd) and Cetuximab in People With Colorectal Cancer

    Not yet recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2026Primary completion 2029-06 NCT07691489

    trastuzumab deruxtecan FDA EU

    A Phase 2 Trial of Trastuzumab Deruxtecan in Combination With Cetuximab in HER2-low Metastatic Colorectal Cancer That Has Progressed on Standard Therapies

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Colorectal Cancer, Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum

  18. CVL006 Combination Therapy in Advanced Solid Tumors

    Not yet recruiting Phase 1/2 Convalife Started 2025Primary completion 2028-08 NCT07157956

    pemetrexedcarboplatinsacituzumab tirumotecantrastuzumab deruxtecanenfortumab vedotin

    …rm2.1, Arm2.2, Arm2.5 and Arm2.7: For NSCLC Arm2.1: Non-squamous, wild-type NSCLC Arm2.2: EGFRm nsqNSCLC Arm2.3: Malignant pleural mesothelioma Arm2.4: triple-negative breast cancer Arm…

    EGFR exon 19 deletion / L858RAdvanced Solid Tumor

  19. A Phase II Study of HLX22 in Combination With Trastuzumab Deruxtecan in HER2-low, Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Patients

    Recruiting Phase 2 Henlius Started 2025Primary completion 2027-06 NCT06832202

    HLX22trastuzumab deruxtecan FDA EU

    With histologically confirmed diagnosis of HER2-low, Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer.

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)HER2-low Hormone Receptor Positive Breast Cancer

  20. Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype

    Recruiting Phase 2 MedSIR Started 2025Primary completion 2027-01 NCT06486883

    trastuzumab deruxtecan FDA EUCDK4/6i plus ET

    Evidence of HER2-low expression (1+ by immunohistochemistry (IHC) or 2+ and negative by an in situ hybridizati…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced Breast Cancer, Advanced Breast Carcinoma, Hormone Receptor Positive Breast Carcinoma

  21. T-DXd With or Without Bevacizumab for HER2-low Breast Cancer With Brain Metastasis

    Recruiting Phase 2 Fudan University Started 2025Primary completion 2027-09 NCT07150208

    bevacizumabtrastuzumab deruxtecan FDA EU

    Histologically confirmed invasive HER2-low expressing breast cancer (specific definition: breast cancer patients with low expression…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer With Brain Metastasis, HER2-low Expressing Breast Cancer

  22. ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer

    Recruiting Phase 1/2 Kristina A. Fanucci Started 2025Primary completion 2028-06 NCT07198724

    elacestranttrastuzumab deruxtecan FDA EUtrastuzumab

    Participants must have a histologically or cytologically confirmed diagnosis of HR+/HER2-low metastatic or unresectable locally advanced breast cancer, defined as ER ≥ 10%, any PR in…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Metastatic Breast Cancer, HER2 Low Breast Carcinoma, HER2-negative Breast Cancer, Breast Cancer

  23. A Study Evaluating the Efficacy and Safety of De Trastuzumab (T-DXd) in Combination with Immunotherapy for the Neoadjuvant Treatment of HR-positive HER2 Low-expressing Chinese Patients with Early-stage Breast Cancer

    Not yet recruiting Phase 2 Guangzhou Women and Children's Medical Center Started 2025Primary completion 2028-01 NCT06733233

    trastuzumab deruxtecan FDA EU

    …ab (T-DXd) in Combination with Immunotherapy for the Neoadjuvant Treatment of HR-positive HER2 Low-expressing Chinese Patients with Early-stage Breast Cancer

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, Estrogen Receptor-Positive, HER2 Low Breast Cancer

  24. A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma

    Recruiting Phase 2 AstraZeneca Started 2025Primary completion 2027-11 NCT07069712

    AZD0901Rilvegostomigtrastuzumab deruxtecancapecitabinefluorouracilFLOT Chemotherapyleucovorin

    Participants who are CLDN18.2-positive in Sub-study 1 or HER2-positive in Sub-study 2

    Claudin 18.2 expressionGastroesophageal Adenocarcinoma

  25. Perioperative Therapies in Locally Advanced Unresectable Gastric Cancer

    Recruiting Phase 2 Jeeyun Lee Started 2025Primary completion 2028-10 NCT06630130

    trastuzumab deruxtecancapecitabineRilvegostomigdurvalumabSonesitatug Vedotinoxaliplatin

    In Cohort A＆B, HER2 positive (HER2 IHC 3+ or HER2 IHC 2+/ISH positive) In Cohort C＆D, CLDN18.2 positive

    Claudin 18.2 expressionStomach Neoplasms

  26. Efficacy and Safety of T-DXd in HER2-mutant Advanced Lung Cancer Patients With Asymptomatic Brain Metastases

    Enrolling by invitation Phase 2 Yonsei University Started 2024Primary completion 2026-12 NCT06250777

    trastuzumab deruxtecan

    Activating HER2-mutation documented by NGS in tissue or plasma (include activating HER2 mutation in exon 19 or 20, i.e. , Exon 20: A775\_G776insYVMA insertion/duplication

    EGFR exon 19 deletion / L858RHER2 (ERBB2) activating mutationNon Small Cell Lung Cancer

  27. Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer

    Recruiting Phase 1/2 Jeeyun Lee Started 2024Primary completion 2025-12 NCT06085755

    trastuzumab deruxtecan FDA EUafatinib

    HER2-low (HER2 1+, HER2 2+ (SISH negative))

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Stomach Neoplasm

  28. TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd

    Recruiting Phase 2 Ana C Garrido-Castro, MD Started 2024Primary completion 2028-01 NCT06533826

    trastuzumab deruxtecan FDA EUdatopotamab deruxtecan

    Participants must have history of HER2-low or HER2-0 breast cancer per local testing, and no known history of HER2-positive breast c…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, HER2-low Breast Cancer, Metastatic Breast Cancer, HER2-negative Breast Cancer

  29. T-DXd Therapy for HER2-low Breast Cancer Patients With Brain Metastases

    Active, not recruiting Phase 2 MedSIR Started 2024Primary completion 2026-11 NCT06048718

    trastuzumab deruxtecan FDA EU

    T-DXd Therapy for HER2-low Breast Cancer Patients With Brain Metastases

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, Metastatic Breast Cancer

  30. T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

    Recruiting Phase 1/2 Yonsei University Started 2024Primary completion 2025-12 NCT05894824

    trastuzumab deruxtecan FDA EUramucirumab

    Histologically or cytologically proven metastatic or locally advanced HER2 low gastric or GEJ adenocarcinoma: The definition of HER2 low is 1+ by immunohistochemistry (…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Gastric Cancer, Gastroesophageal Junction (GEJ) Cancer

  31. Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer

    Recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2023Primary completion 2027-09 NCT06058988

    trastuzumab deruxtecan

    Her2 mutations must be described to be activating, occur at a known hotspot (e.g. exon 20 insertions, S310, G660, R678, L755, D769, L777), or involve the transmembrane, juxtamembrane or tyr…

    EGFR exon 20 insertionHER2 (ERBB2) activating mutationHER2-low / ultralow (IHC 1+ or 2+/ISH-)Brain Cancer, Glioblastoma, Metastatic Cancer, Leptomeningeal Metastasis

  32. Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)

    Recruiting Phase 2 Gruppo Oncologico del Nord-Ovest Started 2023Primary completion 2027-05 NCT05845450

    trastuzumab deruxtecandurvalumabpanitumumab FDAbotensilimabbalstilimabsotorasib FDA EUVorbipiprantnivolumabamivantamab

    COHORT 8: pMMR/MSS status and KRAS G12C mutation, absence of HER2 overexpression/amplification and wild-type status for BRAF.

    KRAS G12CMSI-H / dMMRColorectal Cancer, Resectable Colorectal Carcinoma

  33. Trastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer

    Recruiting Phase 2 Yonsei University Started 2023Primary completion 2026-10 NCT06837792

    trastuzumab deruxtecan FDA EUControl treatment arm

    …hase II Study of Trastuzumab Deruxtecan Versus Endocrine Therapy of Physician's Choice in Low-HER2 Expressing Hormone Receptor-positive Advanced Breast Cancer Patients

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Hormone Receptor(HR)-Positive, Low HER2 Advanced Breast Cancer Patients (HER2 IHC 1+ or 2+ & ISH Negative)

  34. TRUDI: TDXD+Durva in HER2+/Low IBC

    Recruiting Phase 2 Filipa Lynce, MD Started 2023Primary completion 2027-12 NCT05795101

    trastuzumab deruxtecan FDA EUdurvalumab

    HER2-positive status as determined locally by the current ASCO/CAP guidelines or HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) (note: ISH may be det…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Invasive Breast Cancer, Inflammatory Breast Cancer Stage III, HER2-positive Breast Cancer, HER2 Low Breast Adenocarcinoma

  35. Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers

    Recruiting Phase 2 NRG Oncology Started 2023Primary completion 2028-07 NCT05408845

    docetaxeltrastuzumabtrastuzumab deruxtecan FDA EUtrastuzumab emtansine

    Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8

  36. A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

    Active, not recruiting Phase 2 AstraZeneca Started 2022Primary completion 2024-11 NCT05246514

    trastuzumab deruxtecan FDA EU

    …Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

    HER2 (ERBB2) activating mutationHER2-mutant Non-Small Cell Lung Cancer

  37. Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

    Recruiting Phase 1/2 AstraZeneca Started 2022Primary completion 2028-02 NCT05417594

    AZD9574temozolomide[11C]AZ1419 3391trastuzumab deruxtecandatopotamab deruxtecan

    …ced or metastatic disease and evidence of a predicted loss of function germline or tumour mutation in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D,

    BRCA1/2 mutationIDH1/2 mutationHER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced Solid Malignancies

  38. Phase 2 Study of Trastuzumab Deruxtecan in the Neoadjuvant Treatment, or Trastuzumab Deruxtecan Plus Capecitabine Plus Durvalumab(MEDI4736) in the Preoperative and Postoperative Adjuvant Treatment for Patients With HER2 Positive Gastric and Gastroesophageal Junction Adenocarcinoma

    Active, not recruiting Phase 2 National Cancer Center Hospital East Started 2022Primary completion 2028-03 NCT05034887

    trastuzumab deruxtecan FDA EUdurvalumabcapecitabine

    Has HER2 overexpression (IHC3+, or IHC2+ and ISH positive \[FISH or DISH\]). (HER2 Low expression: IHC1+, or IHC2+ and ISH-negative \[FISH or DISH\] with HER2-ECD \> 11.6 ng/mL…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma

  39. A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations

    Active, not recruiting Phase 2 AstraZeneca Started 2020Primary completion 2023-01 NCT04639219

    trastuzumab deruxtecan FDA EU

    Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772\_A775dup / A775\_G776insYVMA, L755…

    HER2 (ERBB2) activating mutationAdvanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast

  40. Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)

    Active, not recruiting Phase 2 AstraZeneca Started 2020Primary completion 2027-05 NCT04379596

    fluorouracilcapecitabinedurvalumaboxaliplatintrastuzumabtrastuzumab deruxtecan FDA EUcisplatinpembrolizumabVolrustomigRilvegostomig

    … 3b,4b and Part 5, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Gastric Cancer

  41. Trastuzumab Deruxtecan Alone or in Combination With Anastrozole for the Treatment of Early Stage HER2 Low, Hormone Receptor Positive Breast Cancer

    Recruiting Phase 2 Jonsson Comprehensive Cancer Center Started 2020Primary completion 2026-12 NCT04553770

    anastrozoletrastuzumab deruxtecan FDA EU

    Tumor is HER2-low by immunohistochemistry (IHC), defined as 1+ or 2+, confirmed by central testing (central…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Early-stage Breast Cancer, Hormone Receptor Positive Breast Carcinoma, Invasive Breast Cancer, Stage II Breast Cancer

  42. A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer

    Active, not recruiting Phase 1/2 AstraZeneca Started 2018Primary completion 2024-11 NCT03742102

    durvalumabcapivasertiboleclumabpaclitaxeltrastuzumab deruxtecan FDA EUdatopotamab deruxtecan

    …provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Triple Negative Breast Neoplasms

  43. Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer

    Recruiting Phase 1 National Cancer Institute (NCI) Started 2026Primary completion 2028-01 NCT07137416

    Pidnarulextrastuzumab deruxtecan FDA EU

    HR+ HER2 positive/low/ultralow breast cancer or triple negative breast cancer (TNBC) HER2-low breast cancer, with HER2 positive defined by the current American Society of Clinical Onc…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Invasive Breast Carcinoma, Locally Advanced Breast Carcinoma

  44. A Study of Subcutaneous Trastuzumab Deruxtecan in Participants With Metastatic Solid Tumors

    Recruiting Phase 1 Daiichi Sankyo Started 2025Primary completion 2028-12 NCT07015697

    trastuzumab deruxtecan FDA EU

    NSCLC, HER2 mut: adults with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) m…

    HER2 (ERBB2) activating mutationHER2-low / ultralow (IHC 1+ or 2+/ISH-)Recurrent or Metastatic Solid Tumors

  45. Anlotinib With Trastuzumab Deruxtecan for Previously Treated HER2-Low Advanced Breast Cancer

    Recruiting Phase 1 Fudan University Started 2024Primary completion 2026-12 NCT06331169

    anlotinibtrastuzumab deruxtecan FDA EU

    Has a history of low HER2 expression (IHC 1+\& IHC 2+/ISH- or 0\<IHC\<1+).

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Status may be outdated, last updated 2024-08-30Breast Cancer

  46. A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors

    Active, not recruiting Phase 1 Daiichi Sankyo Started 2024Primary completion 2028-11 NCT06244485

    Valemetostat tosylatetrastuzumab deruxtecan FDA EUdatopotamab deruxtecan

    Has a history of low HER2 expression, defined as immunohistochemistry (IHC) 2+ /in situ hybridization (ISH)-negative or IHC 1+…

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced Solid Tumor

  47. ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

    Active, not recruiting Phase 1 Enliven Therapeutics Started 2023Primary completion 2026-07 NCT05650879

    ELVN-002trastuzumab deruxtecan FDA EUtrastuzumab emtansine

    HER2 mutation identified by tissue (fresh or archival) or ctDNA.

    HER2 (ERBB2) activating mutationHER2 Mutant Non-small Cell Lung Cancer, HER2-positive Metastatic Breast Cancer, HER2 Gene Mutation, HER2 Amplification

  48. FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3

    Recruiting Phase 1 Eli Lilly Started 2023Primary completion 2027-06 NCT05614739

    Vepugratinibpembrolizumabenfortumab vedotintrastuzumab deruxtecanmidazolamDigoxinRosuvastatin

    …, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.

    FGFR3 alteration (mutation or fusion)Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms

  49. Phase 1b Study of EZH1/2 Inhibitor Valemetostat in Combination With Trastuzumab Deruxtecan in Subjects With HER2 Low/Ultra-low/Null Metastatic Breast Cancer

    Active, not recruiting Phase 1 M.D. Anderson Cancer Center Started 2023Primary completion 2030-12 NCT05633979

    trastuzumab deruxtecan FDA EUValemetostat

    Pathologically confirmed HER2 low/ultra-low/null breast cancer.

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer

  50. Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene

    Recruiting Phase 1 National Cancer Institute (NCI) Started 2022Primary completion 2028-07 NCT05372614

    neratinibtrastuzumab deruxtecan FDA EU

    A known HER2 activating mutation

    HER2 (ERBB2) activating mutationMetastatic Malignant Solid Neoplasm, Metastatic Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8

  51. DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer

    Active, not recruiting Phase 1 Daiichi Sankyo Started 2020Primary completion 2025-07 NCT04042701

    trastuzumab deruxtecan FDA EUpembrolizumab

    Pathologically documented, locally advanced/metastatic HER2-mutant NSCLC

    HER2 (ERBB2) activating mutationHER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer, Non-small Cell Lung Carcinoma

  52. A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

    Active, not recruiting Phase 1 AstraZeneca Started 2020Primary completion 2023-08 NCT04556773

    trastuzumab deruxtecan FDA EUdurvalumabpaclitaxelcapivasertibanastrozolefulvestrantcapecitabine

    Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Metastatic Breast Cancer

  53. Exploration of the Safety and Efficacy of T-DXd Concurrent With Brain Radiotherapy in Patients With Brain Metastases HER2-positive/HER2-low Advanced Breast Cancer

    Recruiting No phase QIAO LI Started 2025Primary completion 2026-07 NCT07117864

    trastuzumab deruxtecan FDA EU

    HER2-positive or HER2-low invasive breast cancer, defined as:

    HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer