FDA Approves Trastuzumab Deruxtecan in HER2+ Solid Tumors

• The FDA has granted accelerated approval to trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with inoperable or metastatic tumors that express HER2 who have received prior systemic treatment and have no satisfactory alternative treatment options.
• The accelerated approval is supported by data from the DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831) trials.
• This tumor agnostic indication was granted accelerated approval based on objective response rate (ORR) and duration of response (DOR) data.

The FDA granted accelerated approval to T-DXd for the treatment of patients with HER2-positive tumors that are unresectable or metastatic that have been treated with prior systemic treatment and have no satisfactory alternative treatment options.¹

“Trastuzumab deruxtecan is already known to be active as an antibody-drug conjugate [ADC] and we already know that it has efficacy in the setting of HER2-low, as well as HER2-positive breast cancer, and in HER2-positive gastric cancer, as well as lung cancer,” explained Funda Meric-Bernstam, MD, in an interview with Targeted Oncology^TM.

The tumor agnostic indication is supported by ORR findings from the DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 studies.

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In DESTINY-PanTumor02, the ORR was 51.4% (95% CI, 41.7%-61.0%) and median duration of response (DOR) was 19.4 months (range, 1.3-27.9+). In DESTINY-Lung01, ORR was 52.9% (95% CI, 27.8%-77.0%) and median DOR was 6.9 months (range, 4.0-11.7+). In DESTINY-CRC02, ORR was 46.9% (95% CI, 34.3%-59.8%), and DOR was 5.5 months (range, 1.3-9.7+).

Regarding safety, the most common adverse events (≥20%) included decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, fatigue, decreased lymphocyte count, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, decreased appetite, alopecia, diarrhea, decreased blood potassium, constipation, decreased sodium, stomatitis, and upper respiratory tract infection.

T-DXd was granted priority review in January 2024.² In August 2023, the FDA granted breakthrough therapy designations to T-DXd for adult patients with unresectable or metastatic HER2-positive solid tumors who progressed after their prior treatment and for whom no effective alternative therapies exist and the treatment of patients with HER2-positive metastatic colorectal cancer who have previously undergone treatment with 2 or more regimens.²

T-DXd has already received FDA approval for use in other cancers, including patients with HER2-positive metastatic breast cancer, unresectable or metastatic HER2-low breast cancer, HER2-positive gastric cancer, HER2-mutant non-small cell lung cancer, and more.³

“HER2 amplification [goes beyond] gastric cancer and breast cancer. Three to 5% of patients with solid tumors have a HER2 amplification, so it is an unmet medical need,” said Hiroya Taniguchi, MD, in an interview with Targeted Oncology^TM.

REFERENCES:

1. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. News release. FDA. April 5, 2024. Accessed April 5, 2024. https://tinyurl.com/47uuetzn

2. Enhertu granted priority review in the US for patients with metastic HER2-positive solid tumors. News release. AstraZeneca. January 29, 2024. Accessed April 5, 2024. http://tinyurl.com/mty53a77

3. ENHERTU® granted two breakthrough therapy designations in U.S. for patients across multiple HER2 expressing cancers. News release. Daiichi Sankyo and AstraZeneca. August 31, 2023. Accessed April 3, 2024. https://tinyurl.com/y3ejnr75