FDA Grants Breakthrough Therapy Designation to Patritumab Deruxtecan for Metastatic EGFR-Mutated Non-Small Cell Lung Cancer


The Breakthrough Therapy Designation was granted based on data from the dose escalation portion of 2 expansion cohorts of a 3-cohort phase 1 study.

Officials with the FDA have granted Breakthrough Therapy Designation to patritumab deruxtecan (HER3-DXd; Daiichi Sankyo) for the treatment of patients with metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on or after treatment with a third generation tyrosine kinase inhibitor and platinum-based therapies.

Patritumab deruxtecan is comprised of a fully human anti-ERBB3 (HER3) immunoglobulin G1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. It is currently being investigated across multiple cancers as both a monotherapy and in combination with other anticancer treatments.

HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival, according to a press release. Approximately 25% to 30% of lung cancers have an EGFR-activating mutation, including approximately 83% of all NSCLC tumors. Currently, no HER3 directed medicines are approved for the treatment of cancer.

According to the press release, lung cancer is the second most common form of the disease and the leading cause of cancer-related mortality globally, with 80% to 85% of diagnoses classified as NSCLC. Although the efficacy of targeted therapy with EGFR tyrosine kinase inhibitors is well-established in the treatment of advanced EGFR-mutated NSCLC, the development of a broad range of resistance mechanisms commonly leads to disease progression.

After failure of an EGFR tyrosine kinase inhibitor, platinum-based chemotherapy has a limited efficacy with progression-free survival (PFS) of approximately 4.4 to 6.4 months, and subsequent salvage therapies have PFS of between 2.8 and 3.2 months.

“The Breakthrough Therapy Designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic [tyrosine kinase inhibitor]-resistant, EGFR-mutated non-small cell lung cancer,” said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, in the press release.

The Breakthrough Therapy Designation for patritumab deruxtecan was granted based on data from the dose escalation portion of 2 expansion cohorts of a 3-cohort phase 1 study. The dose expansion part of the study is evaluating patritumab deruxtecan at 5.6 mg/kg every 3 weeks in 3 cohorts.

Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking 1 or more EGFR tyrosine kinase inhibitors and 1 or more platinum-based chemotherapy regimens. Cohort 2 includes patients with squamous or non-squamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and following an anti-programmed death cell 1 (anti-PD-1) or anti-programmed cell death ligand 1 (anti-PD-L-1) antibody regimen. Finally, cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and NSCLC.

The primary objective of the dose expansion part of the study is to assess the efficacy of patritumab deruxtecan as measured by confirmed objective response rate. Secondary endpoints include overall response rate, safety, and pharmacokinetics, according to the press release.


Patritumab Deruxtecan Granted US FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer. News release. BusinessWire; December 23, 2021. Accessed January 3, 2021. https://www.businesswire.com/news/home/20211222005517/en

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