The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Patritumab deruxtecan (HER3-DXd) demonstrated antitumor activity in patients with heavily pretreated, metastatic or locally advanced EGFR-mutant non-small cell lung cancer (NSCLC) in a phase 1 study.

These results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute in Boston.

The study ( Identifier: NCT03260491) was designed to evaluate the safety and antitumor activity of HER3-DXd, which consists of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload (an exatecan derivative) via a tetrapeptide-based cleavable linker.

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The study had dose-escalation and dose-expansion cohorts. Dr Jänne presented efficacy data for the 57 patients who received the recommended expansion dose of HER3-DXd (5.6 mg/kg every 3 weeks) and safety data for 81 patients who received all doses.

All patients had locally advanced or metastatic EGFR-mutant NSCLC and had previously received EGFR tyrosine kinase inhibitors (TKIs). The median age was 65 years in the efficacy cohort and 64 years in the safety cohort (overall range, 40-80 years).

Patients in both cohorts had received a median of 4 (range, 1-9) prior lines of systemic therapy. Most patients — 86% of the efficacy cohort and 89% of the safety cohort — had received prior osimertinib.

About half of patients in each cohort — 47% in the efficacy cohort and 53% in the safety cohort — had a history of central nervous system (CNS) metastases.

In the efficacy cohort, the median follow-up was 10.2 months. The confirmed overall response rate (ORR) was 39%, and the median progression-free survival (PFS) was 8.2 months.

Among patients who had received prior osimertinib, the ORR was 39%, and the median PFS was 8.2 months. Among patients with a history of CNS metastases, the ORR was 32%, and the median PFS was 8.2 months.

Dr Jänne noted that responses were observed across EGFR TKI resistance mechanisms and a wide range of baseline HER3 expression levels. Furthermore, HER3-DXd had a “tolerable and manageable safety profile,” he said

Treatment-related adverse events (AEs) occurred in 96% of patients in the safety cohort. Grade 3 or higher treatment-related AEs occurred in 47% of patients. The most common grade 3 or higher AEs were thrombocytopenia, neutropenia, and fatigue.

Treatment-emergent AEs leading to discontinuation occurred in 9% of patients. There were no treatment-related deaths.

“In summary, HER3-DXd addresses an unmet need in EGFR TKI-resistant, EGFR-mutant non-small cell lung cancer,” Dr Jänne said.

He noted that additional studies of HER3-DXd in EGFR-mutant NSCLC are underway ( Identifiers: NCT04676477 and NCT04619004).

Disclosures: This research was supported by Daiichi Sankyo, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Jänne PA, Baik CS, Su W-C, et al. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39:(suppl 15; abstr 9007). doi:10.1200/JCO.2021.39.15_suppl.9007