T-DXd Wins EU Approval for Previously Treated, HER2+ Metastatic Solid Tumors

The European Union (EU) has approved trastuzumab deruxtecan (Enhertu) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment and who have no satisfactory treatment options.¹

The European Commission’s regulatory decision followed a positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use, and it was supported by subgroup data from the phase 2 DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT04644237), and DESTINY-CRC02 (NCT04744831) trials.

The EU decision also followed accelerated approval granted to fam-trastuzumab deruxtecan-nxki by the FDA in April 2024 for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic therapy and have no satisfactory alternative treatment options.²

“HER2 overexpression occurs across multiple tumor types and is associated with aggressive disease and a poor prognosis,” Benedikt Westphalen, MD, head of the Precision Oncology Program at the Comprehensive Cancer Center of the University of Munich in Germany, stated in a news release.¹ “Until now, HER2-directed therapies were only available for specific tumor types. The approval of trastuzumab deruxtecan as a tumor-agnostic therapy opens a new treatment option for patients with HER2-positive cancers regardless of where the tumor originated.”

What data helped support the EU pan-tumor approval of T-DXd?

Findings from DESTINY-PanTumor02 showed that patients with previously treated, HER2-positive (IHC 3+) solid tumors (n = 111) achieved a confirmed objective response rate (ORR) of 52.3% (95% CI, 42.6%-61.8%) and median duration of response (DOR) of 21.1 months (95% CI, 10.6-25.0). This group of patients had biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and other tumor types.

Patients with HER2-positive (IHC 3+) non–small cell lung cancer (NSCLC) treated with T-DXd in DESTINY-Lung01 (n = 17) achieved a confirmed ORR of 52.9% (95% CI, 27.8%-77.0%) and median DOR of 6.9 months (95% CI, 4.0-9.8).

In DESTINY-CRC02, T-DXd generated a confirmed ORR of 46.9% (95% CI, 34.3%-59.8%) and median DOR of 5.5 months (95% CI 4.2-8.1) in patients with previously treated, HER2-positive (IHC 3+) colorectal cancer (CRC; n = 64).

A pooled safety analysis for patients treated with T-DXd across these 3 studies showed that the antibody-drug conjugate’s safety profile was consistent with previously clinical trial experience, and no new safety signals were identified.

How was DESTINY-PanTumor02 designed?

DESTINY-PanTumor02 was a multicenter, open-label, non-randomized study that enrolled patients at least 18 years of age with locally advanced, unresectable, or metastatic solid tumors who experienced disease progression following prior treatment or who have no satisfactory alternative treatment option.³ Notably, prior HER2-targeted therapy was allowed.

The 2-part study included tumor-specific cohorts. In part 1, patients were required to have HER2-positive disease (IHC 3+ or 2+) per local or central assessment, and patients were enrolled to the following cohorts based on tumor type:

• Cohort 1: Biliary tract cancer
• Cohort 2: Bladder cancer
• Cohort 3: Cervical cancer
• Cohort 4: Endometrial cancer
• Cohort 5: Epithelial ovarian cancer
• Cohort 6: Pancreatic cancer
• Cohort 7: Rare tumors excluding tumors included in other part 1 cohorts and breast cancer, NSCLC, gastric cancer, and CRC

In part 2, patients needed to meet HER2 IHC/in situ hybridization (ISH) criteria per by central assessment to be enrolled in one of the following predefined cohorts:

• Cohort A: Metastatic or advanced solid tumors that are HER2-positive (IHC 3+), excluding breast, gastric cancer, and CRC and including NSCLC
• Cohort B: Metastatic or advanced solid tumors that are HER2-positive (IHC 2+/ISH+), excluding breast, gastric cancer, and CRC, and including NSCLC
• Cohort C: Metastatic or advanced HER2-positive (ICH 2+ or 1+) endometrial cancer
• Cohort D: Metastatic or advanced HER2-positive (IHC 2+ or 1+) ovarian cancer
• Cohort E: Metastatic or advanced HER2-positive (IHC 2+ or 1+) cervical cancer

All enrolled patients across both parts of the study received T-DXd monotherapy.

ORR served as the trial’s primary end point. Secondary end points included DOR, disease control rate, progression-free survival (PFS), 6- and 12-month PFS rate, overall survival (OS), 6- and 12-month OS rate, safety, and pharmacokinetics.

References

1. Enhertu approved in the EU as first tumour agnostic HER2-directed therapy and antibody drug conjugate for patients with previously treated HER2-positive metastatic solid tumours. News release. AstraZeneca. June 29, 2026. Accessed June 29, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/enhertu-approved-in-eu-for-her-solid-tumours.html
2. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. FDA. April 5, 2024. Accessed June 29, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2
3. A phase 2 study of T-DXd in patients with selected HER2 expressing tumors (DPT02). ClinicalTrials.gov. Updated April 9, 2026. June 29, 2026. https://clinicaltrials.gov/study/NCT04482309