Patritumab Deruxtecan Receives FDA Breakthrough Therapy Designation for EGFR-Mutated, TKI-Resistant Non-Small Cell Lung Cancer

Today, Daiichi Sankyo announced that the U.S. FDA has granted patritumab deruxtecan (HER3-DXd) Breakthrough Therapy Designation (BTD). This is a potential "first-in-class" HER3-targeted investigational antibody-drug conjugate (ADC) for the treatment of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) who have experienced disease progression during or after treatment with third-generation tyrosine kinase inhibitors (TKIs) and platinum-based therapies and carry resistant EGFR mutations.

Lung cancer is the second most common cancer globally and a leading cause of cancer-related deaths, with 80%-85% being non-small cell lung cancer (NSCLC). Approximately 15%-50% of NSCLC patients harbor EGFR mutations. While the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy has been well validated in patients with advanced NSCLC carrying EGFR mutations (approximately 30% of patients), resistance to treatment often leads to disease progression. After EGFR TKI failure, the efficacy of platinum-based chemotherapy is limited, with patients' progression-free survival (PFS) being only about 4.4-6.4 months. About 83% of tumor cells in NSCLC patients with EGFR mutations express the HER3 protein. HER3, a member of the receptor tyrosine kinase EGFR family, is associated with abnormal cell proliferation and survival, potentially correlating with increased metastasis rates, reduced survival, and resistance to standard treatments.

Patritumab deruxtecan is designed using Daiichi Sankyo Company Limited's proprietary DXd ADC technology, consisting of a humanized anti-HER3 antibody linked to a topoisomerase I inhibitor payload through a tetrapeptide linker.

▲Introduction to Patritumab Deruxtecan (U3-1402) (Image Source: Daiichi Sankyo Official Website)

This Breakthrough Therapy Designation is based on positive data currently obtained from a three-cohort Phase 1 clinical trial of the drug. Results presented at the 2021 American Society of Clinical Oncology (ASCO) showed that, among 57 enrolled patients treated with patritumab deruxtecan (5.6 mg/kg), the objective response rate (ORR) reached 39% (CI 95%: 26-52%), the disease control rate was 72% (CI 95%: 59-83%), and the median progression-free survival (PFS) was 8.2 months. In terms of safety, the safety profile in patients receiving the 5.6 mg/kg dose (n=57) was consistent with previous studies.

References:

[1] Patritumab Deruxtecan Granted U.S. FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer. Retrieved December 23, 2021, from https://www.daiichisankyo.com/files/news/pressrelease/pdf/202112/20211223_E1.pdf

(Original text has been abridged)

▽Follow 【WuXi AppTecGermany】WeChat Official Account