Today we’re spotlighting five trials that feature Enhertu (fam-trastuzumab deruxtecan-nxki) as an intervention being evaluated to treat various forms of cancer. Enhertu was first approved by the U.S. Food and Drug Administration (FDA) in December 2019. The drug is a HER2-directed antibody and topoisomerase inhibitor conjugate that’s used to treat forms of breast cancer, lung cancer, solid tumors, and gastric or gastroesophageal junction adenocarcinoma. 

The following spotlight features just five of the many DESTINY trials currently evaluating the effectiveness of trastuzumab deruxtecan (T-DXd) as cancer treatment.

DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/​2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer (DE-01)

Study Details | Source

  • Sponsor: AstraZeneca
  • Official Description: DESTINY-Endometrial01 will investigate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.
  • Interventions: Trastuzumab Deruxtecan, Rilvegostomig, Pembrolizumab, Carboplatin, Paclitaxel, Docetaxel
  • Estimated Enrollment: 600
  • Primary Outcome Measure: Progression-free survival (PFS), as assessed by BICR.
  • Anticipated Primary Completion: January 19, 2029
Study of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy for HER2-Expressing (IHC 3+/​2+) Endometrial Cancer (DESTINY-Endometrial02)

Study Details | Source

  • Sponsor: Daiichi Sankyo
  • Official Description: This study is designed to assess efficacy and safety of T-DXd adjuvant therapy, with or without radiotherapy, post-surgery in anticancer treatment naïve (including neoadjuvant therapy) endometrial cancer with various HER2 expression levels.
  • Intervention(s): Trastuzumab Deruxtecan, Chemotherapy
  • Estimated Enrollment: 710
  • Primary Outcome Measure: Disease-Free Survival as Assessed by Blinded Independent Central Review or by Histopathologic Confirmation of Disease Recurrence per Local Assessment.
  • Anticipated Primary Completion: March 2032
Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer (DESTINY-Breast15)

Study Details | Source

  • Sponsor: Daiichi Sankyo
  • Official Description: This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.
  • Intervention: Trastuzumab Deruxtecan
  • Estimated Enrollment: 250
  • Primary Outcome Measure: Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT).
  • Anticipated Primary Completion: October 21, 2027
Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)

Study Details | Source

  • Sponsor: Daiichi Sankyo
  • Official Description: A non-randomized safety run-in phase will be conducted prior to randomization phase to assess the safety of T-DXd in combination with bevacizumab.
  • Interventions: Trastuzumab Deruxtecan, Bevacizumab
  • Estimated Enrollment: 582
  • Primary Outcome Measures: Progression Free Survival by Blinded Independent Central Review (BICR) in the HER2 IHC 3+/2+ population
  • Anticipated Primary Completion: November 1, 2028
Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer (DESTINY-BTC01)

Study Details | Source

  • Sponsor: AstraZeneca
  • Official Description: The purpose of this study is to measure the efficacy and safety of T-DXd with rilvegostomig or T-DXd monotherapy compared with gemcitabine plus cisplatin and durvalumab in patients with advanced treatment naïve HER2-expressing BTC.
  • Interventions: Gemcitabine, Cisplatin, Durvalumab, Trastuzumab Deruxtecan, Rilvegostomig, Agilent HercepTest™ mAb pharmDx, Ventana PD-L1 SP263 assay
  • Estimated Enrollment: 620
  • Primary Outcome Measures: Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig; Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the FAS (HER2 IHC 3+) population.
  • Anticipated Primary Completion: June 12, 2028

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