FDA Grants Accelerated Approval to Fam-Trastuzumab Deruxtecan-Nxki in HER2+ Solid Tumors

The FDA approves fam-trastuzumab deruxtecan-nxki in HER2-positive solid tumors.

The FDA has granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of adults with unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and who have no satisfactory alternative treatment options, the agency has announced.

The efficacy of the drug was determined among 192 patients in three multicenter trials: PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831)

The major efficacy outcome of the trials was confirmed objective response rate (ORR), with duration of response (DOR) serving as an additional efficacy outcome. ORR was 51.4% (95% CI: 41.7, 61.0) and median DOR was 19.4 months (range 1.3, 27.9+) in DESTINY-PanTumor02; those figures were 52.9% (95% CI: 27.8, 77.0) and 6.9 months (range 4.0, 11.7+) in DESTINY-Lung01, and 46.9% (95% CI: 34.3, 59.8) and 5.5 months (range 1.3+, 9.7+) in DESTINY-CRC02.

According to the agency’s announcement, the most common adverse events (AEs), occurred in at least 20% of patients, including laboratory abnormalities, 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.

The recommended dosage is 5.4 mg/kg via intravenous infusion once every 3 weeks until disease progression or unacceptable toxicity.

Continued approval for this indication, the FDA noted in its announcement, “may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).”

Reference

FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. News release. Food and Drug Administration. April 5, 2024. Accessed April 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unres