Daiichi Sankyo's Enhertu® Becomes First HER2-Targeted Therapy Approved in Japan for HER2-Mutant Metastatic Non-Small Cell Lung Cancer

On August 23, Daiichi Sankyo announced that Enhertu® (trastuzumab deruxtecan for injection) has been approved in Japan for the treatment of adult patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) with HER2 (ERBB2) mutations whose disease has progressed after chemotherapy.

Lung cancer is the second most common cancer in Japan, with more than 138,000 confirmed cases in 2020. In Japan, only 18.2% of patients with metastatic NSCLC survive more than three years after diagnosis, resulting in particularly poor prognosis for this group of patients.

The approval by Japan's Ministry of Health, Labour and Welfare (MHLW) was based on the results of the Phase II clinical study DESTINY-Lung02, which were presented at the 2022 European Society for Medical Oncology (ESMO) Annual Meeting. ENHERTU® had previously received "Orphan Drug Designation" from the MHLW for this type of cancer, which also supported its eligibility for priority review.

As assessed by blinded independent central review (BICR) in DESTINY-Lung02, a pre-specified interim analysis showed that Enhertu® (5.4mg/kg) achieved a confirmed objective response rate (ORR) of 53.8% (n=52; 95% confidence interval [CI]: 39.5–67.8) in patients with HER2 (ERBB2) mutation-positive unresectable advanced or recurrent non-small cell lung cancer who had previously received chemotherapy.

In DESTINY-Lung02, the safety profile of Enhertu® was consistent with previous clinical studies, with no new safety issues identified. Treatment-related adverse events (AEs) occurred in 93 patients (92.1%) receiving Enhertu® (5.4mg/kg). The most common treatment-related AEs were nausea (59.4%), decreased neutrophil count (33.7%), anemia (28.7%), decreased appetite (28.7%), fatigue (25.7%), constipation (24.8%), decreased white blood cell count (23.8%), and vomiting (22.8%). In the interim analysis, interstitial lung disease (ILD) was observed in 2.7% of Japanese patients during treatment with Enhertu® (5.4mg/kg).

The efficacy and safety of Enhertu® as neoadjuvant therapy, adjuvant therapy, or first-line metastatic treatment for patients with HER2 (ERBB2) mutated advanced unresectable or recurrent NSCLC have not been established. Enhertu® is only indicated for patients with NSCLC whose tumors have HER2 (ERBB2) mutations confirmed by an approved test.

About Enhertu®

Enhertu® (Trastuzumab Deruxtecan for Injection; known as fam-trastuzumab deruxtecan-nxki in the United States) is a HER2-targeted antibody-drug conjugate (ADC). Enhertu® utilizes Daiichi Sankyo's proprietary DXd-ADC technology and is the leading ADC product in Daiichi Sankyo’s oncology portfolio, as well as the most advanced project on AstraZeneca’s ADC scientific platform. Enhertu is composed of a HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload (a derivative of exatecan) via a stable, cleavable tetrapeptide linker.

Based on the results of the DESTINY-Breast03 study, Enhertu® (5.4mg/kg) has been approved in more than 50 countries/regions for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received (one or more) anti-HER2 treatment regimens in the metastatic setting or during neoadjuvant or adjuvant therapy and experienced disease recurrence during treatment or within 6 months after completing treatment.

Based on the results of the DESTINY-Breast04 study, Enhertu® (5.4mg/kg) has been approved in more than 40 countries/regions for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-) breast cancer who have received prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months after completing adjuvant chemotherapy.

Based on the results of the DESTINY-Lung02 study, Enhertu® (5.4mg/kg) has been approved in Israel and Japan, and has received accelerated approval in the United States for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have HER2 (ERBB2) activating mutations (detected by locally or regionally approved testing methods) and who have previously received one systemic therapy. Confirmation of clinical benefit in confirmatory studies will support the full approval of this indication in the United States.

Based on the results obtained from the DESTINY-Gastric01 and/or DESTINY-Gastric02 studies, Enhertu® (6.4mg/kg) has been approved in more than 30 countries/regions for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received a trastuzumab-based treatment regimen.

Editor: Mu Mian

Disclaimer: This article is a reprint from PharmNet. The images and text are the property of the original author, and the purpose of the reprint is to convey more information. It does not represent the views of this platform. If there are any issues regarding content, copyright, or other problems, please leave a message on this platform, and we will handle it promptly.