NCT04676477

HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer

A Phase 1 Open-Label Study of HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 246 (actual)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety. The primary objectives: Dose Escalation: To assess the safety and tolerability of HER3-DXd (patritumab deruxtecan; U3-1402) and osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib, and to determine the recommended combination dose (RCD). Second-Line Dose Expansion Arm 1 and Arm 1b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. Note: One or both of the study arms may open with one or two distinct dosing schedules. Second-Line Dose Expansion Arm 2: To assess the preliminary antitumor activity of HER3-DXd monotherapy in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. First-Line Dose Expansion Cohorts 3, 4a, and 4b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation without prior systemic treatment for locally advanced or metastatic disease.

Detailed description

Dose Escalation: Population includes subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. The starting combination dose regimen is HER3-DXd 3.2 mg/kg IV every 21 days (Q3W) and osimertinib 80 mg orally (PO) once daily. At least 3 to 6 subjects will be enrolled in each cohort. Dose Expansion: Two subject populations will be evaluated in the Dose Expansion Part: * Second-Line: Subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib * First-Line: Subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation, and without prior systemic therapy for advanced or metastatic disease. Note: The first line expansion will only be initiated if the RCD includes osimertinib 80 mg PO once daily.

Conditions

• Non-Small Cell Lung Cancer (NSCLC)

Interventions

Type	Name	Description
DRUG	HER3-DXd	Intravenous infusion at a starting dose of 3.2 mg/kg Q3W
DRUG	HER3-DXd	Intravenous infusion at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)
DRUG	Osimertinib	Oral administration at 40 mg or 80 mg once daily
DRUG	Osimertinib	Oral administration at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)
DRUG	HER3-DXd	Intravenous infusion 5.6 mg/kg Q3W
DRUG	HER3-DXd	Intravenous infusion 4.8 mg/kg Q3W
DRUG	Osimertinib	Oral administration at 80 mg once daily

Timeline

• Start date: 2021-06-11
• Primary completion: 2025-01-31
• Completion: 2027-04-30
• First posted: 2020-12-21
• Last updated: 2025-06-22

Locations

31 sites across 4 countries: United States, Japan, South Korea, Taiwan

Regulatory

• FDA-regulated drug study