Trastuzumab Deruxtecan Shows Clinically Meaningful Response in Non-Small Cell Lung Cancer

Trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) demonstrated clinically meaningful tumor responses in previously treated patients with human epidermal growth factor receptor 2 mutant (HER2m) unresectable and/or metastatic non-squamous non­–small cell lung cancer (NSCLC), according to detailed positive results from an interim analysis of the DESTINY-Lung02 phase 2 trial. The results of the trial were presented as a late-breaking presentation at the European Society for Medical Oncology (ESMO) Congress 2022.

“The DESTINY-Lung02 results are consistent with the data previously seen with [trastuzumab deruxtecan] in [NSCLC] and the efficacy demonstrated in this interim analysis, which supported the recent US FDA accelerated approval of [trastuzumab deruxtecan] in patients with HER2[m] [NSCLC], reinforces the potential to establish this medicine as a treatment option for these patients. These data will help inform future regulatory submissions worldwide with the goal of continuing to offer this innovative medicine to as many patients as possible,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, said in a statement.

Trastuzumab deruxtecan is a specifically engineered HER2-directed antibody drug conjugate. At the pre-specified interim analysis of DESTINY-Lung02, individuals administered trastuzumab deruxtecan at a dose of 5.4 mg/kg or 6.4 mg/kg demonstrated meaningful activity.

Investigators found a confirmed objective response rate of 53.8% and 42.9% in the 5.4 mg/kg arm and 6.4 mg/kg arm, respectively. Additionally, there was 1 complete response observed in each arm, with 27 partial responses in the 5.4 mg/kg arm and 11 in the 6.4 mg/kg arm.

“DESTINY-Lung02 reinforces HER2 as an actionable mutation in patients with metastatic [NSCLC] and further demonstrates that [trastuzumab deruxtecan] provides a clinically meaningful tumor response for these patients who have historically had limited treatment options. The response seen in this trial, along with the disease control observed support [trastuzumab deruxtecan] as a potential treatment option in this type of [NSCLC],” Koichi Goto, MD, a medical oncologist and investigator at the National Cancer Center Hospital East in Kashiwa, Japan, said in a statement.

At the pre-specified interim analysis, a median duration of response (DoR) was not reached in the 5.4 mg/kg arm and was 5.9 months in the 6.4 mg/kg arm. Due to the median DoR not being reached in the 5.4 mg/kg arm, an additional 90-day follow-up response analysis was conducted.

Investigators found that [trastuzumab deruxtecan] demonstrated a confirmed ORR of 57.7% and a median DoR of 8.7 months, with a complete response in 1.9% of individuals and partial responses in 55.8% of individuals. Furthermore, investigators observed a favorable safety profile for the 5.4 mg/kg arm with no safety signals identified at either dose.

The most common treatment-related adverse events grade 3 or higher were anemia, leukopenia, and neutropenia. The safety profile for both doses was also consistent with the overall safety profile of trastuzumab deruxtecan. Further, the 5.4 mg/kg dose demonstrated a favorable safety profile for this patient population.

Reference

DESTINY-Lung02 phase II trial shows clinically meaningful efficacy and favorable safety at 5.4mg/kg vs. 6.4mg/kg dose of AstraZeneca and Daiichi Sankyo’s Enhertu in HER2-mutant disease. News release. AstraZeneca. September 11, 2022. Accessed September 12, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-continues-to-demonstrate-clinically-meaningful-tumour-response-in-patients-with-her2-mutant-metastatic-non-small-cell-lung-cancer.html