EMA Validates Marketing Authorization Application for T-DXd in HER2+ Metastatic Solid Tumors

The European Medicines Agency (EMA) has validated the type II variation marketing authorization application for trastuzumab deruxtecan (T-DXd; Enhertu) for the treatment of adult patients with HER2-positive (immunohistochemistry [IHC] 3+) unresectable or metastatic solid tumors who have received previous treatment and have no satisfactory alternative treatment options.1

This application was based on data with T-DXd from 3 phase 2 trials: DESTINY-PanTumor02 (NCT04482309) in patients with solid tumors such as endometrial, cervical, ovarian, bladder, biliary tract, and pancreatic tumors; DESTINY-CRC02 (NCT04744831) in patients with colorectal cancer (CRC), and DESTINY-Lung01 (NCT03505710) in patients with non–small cell lung cancer (NSCLC). In each of these trials, T-DXd demonstrated clinically meaningful responses across patients with HER2-positive solid tumors. The EMA’s validation of the application begins the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. If approved, T-DXd would be the first HER2-targeted therapy and the first antibody-drug conjugate to have a tumor-agnostic indication in the European Union (EU).

“[T-DXd] has shown a clinically meaningful benefit across several studies in HER2-positive metastatic solid cancers, and this validation by the EMA is an important first step toward bringing this medicine to these patients in the EU,” Ken Takeshita, MD, global head of R&D at Daiichi Sankyo—one of the joint developers of T-DXd—stated in a news release. “We look forward to working with the EMA to potentially secure a tumor-agnostic indication for [T-DXd] in the EU, similar to several other regions of the world where this approval has been received.”

Notably, in April 2024, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for in the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have been previously treated with systemic therapy and have no satisfactory alternative treatment options.2 This regulatory decision was also supported by findings from DESTINY-PanTumor02, DESTINY-CRC01, and DESTINY-Lung01.

What Were the Key Efficacy Findings of the DESTINY-PanTumor02 Trial?

In this trial, patients with HER2-expressing (IHC 3+/2+) locally advanced or metastatic solid tumors who had received at least 1 prior systemic therapy and had no alternative treatment options received T-DXd at 5.4 mg/kg once every 3 weeks.3 Confirmed overall response rate (cORR) served as the primary end point.

At a median follow-up of 12.75 months (range, 0.4-31.6), across all patients (n = 267), the cORR was 37.1% (95% CI, 31.3%-43.2%). Responses were observed in all cohorts, including endometrial cancer (n = 40; ORR, 57.5%; 95% CI, 40.9%-73.0%), cervical cancer (n = 40; ORR, 50.0%; 95% CI, 33.8%-66.2%), ovarian cancer (n = 40; ORR, 45.0%; 95% CI, 29.3%-61.5%), bladder cancer (n = 41; ORR, 39.0%; 95% CI, 24.2%-55.5%), biliary tract cancer (n = 41; ORR, 22.0%; 95% CI, 10.6%-37.6%), pancreatic cancer (n = 45; ORR, 4.0%; 95% CI, 0.1%-20.4%), and other tumors (n = 40; ORR, 30.0%; 95% CI, 16.6%-46.5%).

What Were the Key Efficacy Findings of the DESTINY-CRC02 Trial?

In stage 1 of this trial—the randomized portion—patients with HER2-positive, RAS wild-type or -mutant, BRAF wild-type, unresectable, recurrent, or metastatic CRC were randomly assigned 1:1 to receive T-DXd at 5.4 mg/kg every 3 weeks (n = 40; arm 1) or 6.4 mg/kg every 3 weeks (n = 40; arm 2).4 In stage 2 of this trial—the nonrandomized portion—an additional 42 patients were enrolled to receive T-DXd at the arm 1 dose. The primary end point was cORR.

Among all patients who received T-DXd at the arm 1 dose (n = 82), at a median follow-up of 8.9 months (95% CI, 0.5-17.1), the cORR was 37.8% (95% CI, 27.3%-49.2%). Among patients in arm 2, at a median follow-up of 10.3 months (95% CI, 0.7-16.4), the cORR was 27.5% (95% CI, 14.6%-43.9%).

What Were the Key Efficacy Findings of the DESTINY-LUNG01 Trial?

This trial enrolled patients with previously treated, unresectable, or metastatic centrally confirmed HER2-positive (IHC3+) NSCLC who had relapsed/refractory disease following standard treatment or had no available standard treatment. Among 17 evaluable patients, the cORR was 52.9% (95% CI, 27.8%-77.0%).5

References

1. Enhertu type II variation application validated in the EU for previously treated patients with HER2 positive metastatic solid tumors. News release. Daiichi-Sankyo. September 11, 2025. Accessed September 11, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202509/20250911_E.pdf
2. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. FDA. April 5, 2024. Accessed September 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2
3. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024;42(1):47-58. doi:10.1200/JCO.23.02005
4. Raghav K, Siena S, Takashima A, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. J Clin Oncol. 2023;41(suppl 16):3501. doi:10.1200/JCO.2023.41.16_suppl.3501
5. Enhertu. Prescribing information. Daiichi Sankyo; 2025. Accessed September 11, 2025. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true