Trastuzumab Deruxtecan Receives CDE Priority Review for HER2-Mutant Non-Small Cell Lung Cancer in China

On February 4, the CDE website showed that Daiichi Sankyo's deruxtecan for injection is proposed to be included in the priority review, for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) who have HER2 (ERBB2) activating mutations and have previously received at least one systemic therapy.

Previously, two indications of Trastuzumab Deruxtecan have been launched in China, for HER2-positive adult breast cancer and HER2-low adult breast cancer, respectively.

In September 2023, Daiichi Sankyo and AstraZeneca presented the latest data from the Phase II DESTINY-Lung02 study of trastuzumab deruxtecan in previously treated HER2-mutated metastatic NSCLC patients at the World Conference on Lung Cancer (WCLC). The results demonstrated clinically meaningful and durable tumor responses.

DESTINY-Lung02 enrolled 152 patients at multiple research centers in Asia, Europe, Oceania, and North America, who were randomly assigned in a 2:1 ratio to receive treatment with Trastuzumab Deruxtecan at 5.4 mg/kg (Cohort 1; n=102) or Trastuzumab Deruxtecan at 6.4 mg/kg (Cohort 2; n=50).

According to the assessment results by blinded independent central review (BICR), the confirmed objective response rates (ORR) for the 5.4mg/kg treatment group and the 6.4mg/kg treatment group were 49.0% and 56.0%, respectively. In the 5.4mg/kg treatment group, 1 case (1.0%) of complete response (CR) and 49 cases (48.0%) of partial response (PR) were observed, while in the 6.4mg/kg treatment group, 2 cases (4.0%) of complete response and 26 patients (52.0%) with partial response were observed.

The disease control rate (DCR) was 93.1% in the 5.4mg/kg dose group and 92.0% in the 6.4mg/kg dose group. The median duration of response (DoR) was 16.8 months in the 5.4mg/kg treatment group, and the median duration of response was not reached in the 6.4mg/kg treatment group.

According to BICR assessment, the median PFS was 9.9 months in the 5.4 mg/kg group and 15.4 months in the 6.4 mg/kg group. The median OS was 19.5 months in the 5.4 mg/kg group and not reached in the 6.4 mg/kg treatment group. As of the data cutoff date of December 23, 2022, the median follow-up time was 11.5 months in the 5.4 mg/kg treatment group (n=102) and 11.8 months in the 6.4 mg/kg treatment group (n=50).

Source: Official WeChat Account of Daiichi Sankyo

In terms of safety, the 5.4mg/kg treatment group showed a better safety profile, and no new safety signals were found in either dose.

Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) targeting HER2, designed using Daiichi Sankyo's proprietary DXd ADC technology. It consists of a HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload (exatecan derivative) via a stable tetrapeptide cleavable linker.

Based on the results of the DESTINY-Lung02 study, trastuzumab deruxtecan (5.4 mg/kg) has been approved in 30 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have HER2 (ERBB2) activating mutations as detected by locally or regionally approved testing methods and who have previously received one systemic therapy.

In addition, the indications for HER2-positive breast cancer, HER2-low breast cancer, and HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma for trastuzumab deruxtecan have also been approved for marketing in multiple countries and regions.

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