Patritumab Deruxtecan Demonstrates Continued Activity in Breast/Lung Cancer

Patritumab deruxtecan (HER3-DXd) exhibited on-going clinical activity in patients with previously treated EGFR-mutated metastatic non–small cell lung cancer (NSCLC) in a phase 1 trial (NCT03260491) and those with HER3-expressing metastatic breast cancer in a phase 1/2 trial (NCT02980341), according to a press release from Daiichi Sankyo.

"These results further add to the growing body of evidence that targeting HER3 with patritumab deruxtecan may be a promising therapeutic option for a wide array of patients across several subtypes of metastatic lung and breast cancer," according to the manufacturers of patritumab deruxtecan.

In the phase 1 NSCLC trial, patritumab deruxtecan yielded an objective response rate (ORR) of 40.2% (95% CI, 30.6%-50.4%) in a pooled analysis of 102 patients with EGFR-mutated disease, including 1 complete response (CR), 40 partial responses (PRs), and 39 instances of stable disease (SD).

The treatment also produced a disease control rate (DCR) of 78.4% (95% CI, 69.2%-86.0%) in the NSCLC study and a median duration of response (DOR) of 7.6 months (95% CI, 6.9-14.7) after a median follow-up of 23 months (range, 11.8-36.0). Median progression-free survival (PFS) was 6.4 months (95% CI, 5.3-8.3) and median overall survival (OS) was 15.8 months (95% CI, 10.8-21.5).

In the breast cancer trial, the agent produced confirmed ORRs of 36.2% (95% CI, 24.0%-49.9%) and 28.2% (95% CI, 15.0%-44.9%) in patients with HER2-low (n = 58) and HER2-zero (n = 39) hormone receptor (HR)–positive disease, respectively.

The median DOR was 7.2 months (95% CI, 5.5-not estimable [NE]) and 7.0 months (95% CI, 3.0-NE) in each respective group. The median PFS was 5.8 months (95% CI, 4.1-8.5) and 8.2 months (95% CI, 5.8-9.1) and the median OS was 13.7 months (95% CI, 8.5-20.1) and 14.6 months (95% CI, 11.0-21.0) in the HER2-low and HER2-zero groups, respectively.

Patritumab deruxtecan also produced a confirmed ORR of 20.7% (95% CI, 8.0%-39.7%) in patients with HER2-low triple-negative breast cancer (TNBC; n = 29) and of 26.3% (95% CI, 9.1%-51.2%) in patients with HER2-zero TNBC (n = 19).

Moreover, median DOR was 4.1 months (95% CI, 2.7-6.0) and 8.4 months (95% CI: 4.2-NE) and median PFS was 4.4 months (95% CI, 2.6-5.6) and 8.4 months (95% CI, 3.9-13.9) in the HER2-low and -zero groups, respectively. Additionally, the median OS was 12.7 months (95% CI, 9.2-21.8) and 16.6 months (95% CI, 9.3-23.8) in each respective group.

“Most patients with lung or breast cancer involved in these 2 early-stage trials were heavily pre-treated, underscoring the need for new and innovative treatment options to help improve outcomes,” Mark Rutstein, MD, global head of Oncology Clinical Development at Daiichi Sankyo, said in the press release. “These results further add to the growing body of evidence that targeting HER3 with patritumab deruxtecan may be a promising therapeutic option for a wide array of patients across several subtypes of metastatic lung and breast cancer.”

The global, multicenter, open label phase 1 dose-escalation lung cancer trial, enrolled patients who received a median of 4 prior lines (range, 1-14) of systemic therapy in the locally advanced/metastatic setting.

In total, 58 patients experienced grade 3 or higher treatment-related adverse effects (TRAEs), the most common of which were platelet count decrease (26%) and neutrophil count decrease (21%).

In the global, open-label phase 1/2 trial breast cancer study, patients received a median of 7 prior lines of systemic therapy in the HR-positive, HER2-low, and HER2-zero subgroups; 4 prior lines in the HR-negative, HER2-low subgroup; and 3 prior lines in the HR-negative, HER2-zero subgroup.

Grade 3 or higher TRAEs occurred in 99 patients in Japan and 21 patients in the United States. Treatment-related interstitial lung disease (ILD) occurred in 12 patients from Japan and none from the United States; the majority of ILD events were low-grade.

Patritumab deruxtecan is a first-in-class HER3-directed antibody-drug conjugate. These data were presented at the 2023 Japanese Society of Medical Oncology Annual Meeting.

Reference

Patritumab deruxtecan continues to show encouraging clinical activity in distinct patient populations with metastatic lung and breast cancer in updated results of two early trials. News Release. Daiichi Sankyo. March 19, 2023. Accessed March 20, 2023. https://bwnews.pr/3Z3cPLB