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

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.

Conditions

• Non-Small Cell Lung Cancer (NSCLC)

Interventions

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

Sponsors & Collaborators

• AstraZeneca

  collaborator INDUSTRY

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• Daiichi Sankyo

  lead INDUSTRY

Principal Investigators

• Global Clinical Leader · Daiichi Sankyo

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-11

Primary Completion

2025-01-31

Completion

2027-04-30

FDA Drug

Yes

Countries

• United States
• Japan
• South Korea
• Taiwan

Study Locations