FDA grants accelerated approval to Enhertu for adults with advanced solid tumors
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The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki for the treatment of adults with unresectable or metastatic HER2-positive solid tumors who received previous systemic therapy and lack additional treatment options.
Fam-trastuzumab deruxtecan-nxki (Enhertu; AstraZeneca, Daiichi Sankyo), a HER2-directed antibody-drug conjugate, is approved in the United States for treatment of adults with unresectable or metastatic HER2-positive breast cancer who received two or more prior anti-HER2-based regimens. It also is approved for treatment of adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab (Herceptin, Genentech)-based regimen.
The FDA previously granted the application priority review and breakthrough therapy designation.
The agency based the accelerated approval on efficacy data from three multicenter trials — DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY CRC02 — that, in total, evaluated 192 adults with previously treated unresectable or metastatic HER2-positive solid tumors.
All three trials excluded patients with a history of interstitial lung disease/pneumonitis requiring treatment with steroids or interstitial lung disease/pneumonitis at screening and clinically significant cardiac disease. The studies also excluded adults with active brain metastases or ECOG performance status greater than 1.
Study participants received treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rate served as the main efficacy outcome, with duration of response (DOR) as a secondary outcome measurement. DESTINY-PanTumor02 showed an ORR of 51.4% (95% CI, 41.7-61) and a median DOR of 19.4 months (range, 1.3-27.9). DESTINY-Lung-01 reported an ORR of 52.9% (95% CI, 27.8-77) and a median DOR of 6.9 months (range, 4-11.7). DESTINY-CRC02 showed an ORR of 46.9% (95% CI, 34.3-59.8) and a median DOR of 5.5 months (range, 1.3-9.7).
The most common adverse reactions that occurred in at least 20% of patients included decreases in white blood cell count, hemoglobin, neutrophil count, lymphocyte count, platelet count, blood potassium, sodium and appetite, fatigue, nausea, increases in aspartate aminotransferase, alanine aminotransferase or blood alkaline phosphatase, vomiting, alopecia, diarrhea, constipation, stomatitis and upper respiratory tract infection.
The recommended dosage for trastuzumab deruxtecan is 5.4 mg/kg IV once every 3 weeks until disease progression or unacceptable toxicity.
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