Trastuzumab Deruxtecan Receives FDA Approval for HER2-Positive Solid Tumors

FDA granted accelerated approval to trastuzumab deruxtecan-nxki (Enhertu, AstraZeneca and Daiichi Sankyo, Inc.) for adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who received prior systemic treatment and have no satisfactory alternative treatment options.

The approval comes well in advance of the May 30, 2024, target date. Trastuzumab deruxtecan-nxki is an HER2-directed antibody drug conjugate (ADC), and this approval makes it the first tumor-agnostic approval of a HER2-directed therapy and an ADC.

Funda Meric-Bernstam, MD | Image credit: MD Anderson Cancer Center

“Until the approval of trastuzumab deruxtecan, patients with metastatic HER2 positive solid tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, said in a statement. “Based on the clinically meaningful response rates seen across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2 directed medicine.”

The approval was based on a review of 3 multicenter trials: DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831).

The review was conducted under Project Orbis, which provides a framework for concurrent submission and review of oncology drugs among international partners. FDA collaborated with Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Singapore’s Health Sciences Authority. Reviews at other agencies are ongoing.

This is the second time in 4 months FDA has granted approval to an ADC-based regimen far in advance of its target date. In December, enfortumab vedotin (Padcev, Astellas Pharma) plus pembrolizumab (Keytruda, Merck) was approved to treat locally advanced or metastatic bladder cancer.

Meric-Bernstam presented data from DESTINY-PanTumor02 in June 2023 during the annual meeting of the American Society of Clinical Oncology (ASCO).¹ Results from the phase 2 trial showed trastuzumab deruxtecan could be an option for patients with rarer cancers expressing HER2; these patients often have unmet need, as their numbers are insufficient to make up a tumor-specific study.

“For these patients there are no approved or targeted treatments, and often the disease is refractory to standard-of-care therapies,” Meric-Bernstam said during a press conference at ASCO.

Trastuzumab deruxtecan brought strong responses in endometrial, cervical, ovarian, and urothelial cancers after a median of 9.7 months of follow-up, particularly for patients with HER2+ tumors with immunohistochemistry (IHC) scores of 3+. Only pancreatic tumors with HER2+ expression had poor responses.

“These results advance our clinical understanding of HER2 expression, reaffirm HER2 as an actionable biomarker across a broad range of tumor types, and show that trastuzumab deruxtecan could potentially provide a new treatment option for patients with advanced disease across these tumors, especially in patients with HER2 IHC 3+ or 2+ expression,” she said.


Reference

Meric-Bernstam F, Makker V, Oaknin A. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. J Clin Oncol. 2023;41(suppl 17):abstract LBA3000. doi:10.1200/JCO.2023.41.17_suppl.LBA3000