The Efficacy and Safety of Trastuzumab Deruxtecan in Advanced or Metastatic NSCLC With HER2 Over Expression

The Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) in Advanced or Metastatic NSCLC With Human Epidermal Growth Factor Receptor2(HER2) Overexpression(OE)：A Single-arm, Multicenter, Prospective Study

This is a single arm, multicenter and prospective study to evaluate the efficacy and safety of T-DXd for the treatment in locally advanced, unresectable, or metastatic participants with selected HER2 positive (IHC 3+) NSCLC which are not eligible for curative therapy

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Experimental Group

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chang Yong Zhang; Phone Number: +86 13873123436; Email: zhangyongchang@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female participants must be at least 18 years of age at the time of signing the ICF.
2. Histologically documented Stage III locally advanced and unresectable non-squamous NSCLC not amenable to curative surgery or radiation and/or Stage IV NSCLC.
3. Participants must have HER2 overexpression (IHC 3+).
4. progressed following at least one or two prior systemic treatment.
5. Prior anti-HER2 are eligible except for HER2 ADC.
6. At least 1 measurable lesion by the investigator based on RECIST 1.1.
7. LVEF ≥ 50% within 28 days before enrollment.
8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
9. Adequate organ and bone marrow function within 14 days before enrolment. All parameters must be the most recent results available.
10. Adequate treatment washout period before enrolment.
11. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner.

Exclusion Criteria:

1. Has spinal cord compression or clinically active central nervous system metastases.
2. Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on average of the screening triplicate12-lead ECG.
3. History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
4. Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals
5. Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection or active hepatitis B (hepatitis B virus surface antigen or hepatitis B virus core antibody positive, at screening) or C infection.
6. Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan.
7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.
8. Known allergy or hypersensitivity to study treatment or any of the study drug excipients
9. History of severe hypersensitivity reactions to other monoclonal antibodies.
10. Pregnant or breastfeeding female participants, or participants who are planning to become pregnant.
11. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
12. Any other clinically significant medical conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-DXd group; All participants enrolled in the study will receive the study intervention (T-DXd) 5.4 mg/kg	Drug: Experimental Group; All participants enrolled in the study will receive the study intervention (T-DXd) 5.4 mg/kg as an IV infusion Q3W, on Day 1 of each 3-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of T-DXd by evaluation of Progression-free survival	Endpoints based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) • Progression-free survival (PFS)	UP to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the Overall survival (OS) of T-DXd	To assess the Overall survival (OS) of T-DXd	UP to approximately 3 years
To assess the Objective response rate (ORR) of T-DXd	To assess the Objective response rate (ORR) of T-DXd based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	UP to approximately 3 years
To assess the Disease control rate (DCR) of T-DXd	To assess the Disease control rate (DCR) of T-DXd	UP to approximately 3 years
Safety and toxicity	Adverse events/serious adverse events (AEs/SAEs)	UP to approximately 3 years

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 29, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: ESR-25-22990

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No