Trastuzumab Rezetecan and Adebrelimab, Alone or in Combination, After Chemoradiotherapy for HER2-Altered Unresectable Stage III Lung Cancer

September 17, 2026 updated by: Ming Chen

A Randomized, Open-label, Multicenter, Phase II Study of Trastuzumab Rezetecan With Adebrelimab, Trastuzumab Rezetecan Alone and Adebrelimab Alone as Consolidation Therapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer Harboring HER2 Alterations Without Progression After Definitive Chemoradiotherapy

A randomized phase II study to assess the efficacy and safety of Trastuzumab Rezetecan and/or Adebrelimab as consolidation therapy following chemoradiotherapy in patients with unresectable stage III HER2-altered NSCLC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized, open-label, multi-center phase II study evaluating the efficacy and safety of consolidation therapy with Trastuzumab Rezetecan combined with Adebrelimab versus Trastuzumab Rezetecan monotherapy versus Adebrelimab monotherapy in patients with unresectable stage III NSCLC harboring HER2 alterations (mutation or overexpression) who have not progressed after definitive concurrent or sequential chemoradiotherapy. Eligible patients will be randomized in a 1:1:1 ratio to receive either combination therapy, SHR-A1811 alone, or Adebrelimab alone for up to 12 months. The primary endpoint is progression-free survival (PFS) per RECIST v1.1.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18 years.
  2. ECOG performance status 0-1.
  3. Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC).
  4. Radiologically confirmed unresectable Stage III NSCLC per AJCC 9th edition.
  5. Pathologically confirmed HER2 mutation or HER2 overexpression (IHC 2+ or 3+).
  6. Life expectancy ≥3 months.
  7. Completed at least two cycles of platinum-based chemotherapy (concurrent or sequential) with definitive radiotherapy. Consolidation chemotherapy after radiotherapy is not permitted; chemotherapy with or without immunotherapy before concurrent chemoradiotherapy is permitted.
  8. Total radiotherapy dose 60 Gy ± 10% (54-66 Gy) using IMRT (preferred) or 3D-CRT, with acceptable dosimetric constraints.
  9. Adequate organ and bone marrow function.
  10. Negative pregnancy test for women of childbearing potential within 7 days prior to first dose. Willing to use effective contraception during the study and for 180 days after the last dose.
  11. Signed informed consent form (ICF).

Exclusion Criteria:

  1. Known EGFR-activating mutations or ALK fusions.
  2. Presence of other driver gene mutations with approved targeted therapies available.
  3. Mixed SCLC and NSCLC, large cell neuroendocrine carcinoma, or sarcomatoid carcinoma.
  4. Prior treatment with HER2-targeted ADCs or HER2 TKIs.
  5. Malignant pleural effusion, pericardial effusion, or ascites.
  6. Participation in another clinical trial within 4 weeks or 5 half-lives prior to first dose.
  7. Systemic immunosuppressive therapy within 2 weeks prior to first dose.
  8. Known HIV infection.
  9. Active hepatitis B (HBsAg positive with detectable HBV-DNA and ALT > ULN) or active hepatitis C.
  10. Active autoimmune disease requiring systemic treatment.
  11. Other malignancies within 5 years, except adequately treated cervical carcinoma in situ, basal/squamous cell skin carcinoma, localized prostate cancer, or ductal carcinoma in situ.
  12. Active or history of Grade ≥2 radiation pneumonitis per RTOG/EORTC, or symptomatic interstitial lung disease. Participants with grade 2 radiation pneumonitis that resolves to grade 1 or lower within 14 days without systemic glucocorticoid treatment may undergo screening if the investigator considers there to be no risk of recurrence.
  13. Significant cardiovascular disease.
  14. Severe infection within 4 weeks prior to first dose.
  15. Prior or planned allogeneic bone marrow or solid organ transplantation.
  16. Live attenuated vaccine within 28 days prior to first dose or planned during study. Pregnancy or breastfeeding.
  17. Known hypersensitivity to Adebrelimab, Trastuzumab Rezetecan, or any excipients.
  18. Known history of psychotropic substance abuse, alcohol abuse, or illicit drug use.
  19. Any condition that might impair the subject's ability to comply with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A (Combination Therapy)

Drug: Trastuzumab Rezetecan + Adebrelimab
Drug: Trastuzumab Rezetecan (SHR-A1811) + Adebrelimab

Trastuzumab Rezetecan (4.8mg/kg, iv, d1, Q3W) and Adebrelimab (1200mg, iv, d1, Q3W). Treatment will continue for up to 12 months or until disease progression, unacceptable toxicity, or other criteria for treatment discontinuation are met.
Experimental: Arm B (Targeted Monotherapy)

Drug: Trastuzumab Rezetecan
Drug: Trastuzumab Rezetecan (SHR-A1811)

Trastuzumab Rezetecan (4.8mg/kg, iv, d1, Q3W). Treatment will continue for up to 12 months or until disease progression, unacceptable toxicity, or other criteria for treatment discontinuation are met.
Experimental: Arm C (Immunotherapy Monotherapy)

Drug: Adebrelimab
Drug: Adebrelimab

Adebrelimab (1200mg, iv, d1, Q3W). Treatment will continue for up to 12 months or until disease progression, unacceptable toxicity, or other criteria for treatment discontinuation are met.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Assessed up to approximately 36 months.

Defined as the time from randomization to disease progression or death from any cause, whichever occurs first.
Assessed up to approximately 36 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Assessed up to approximately 60 months.

Defined as the time from randomization to death from any cause.
Assessed up to approximately 60 months.
Objective Response Rate (ORR)
Time Frame: Assessed up to approximately 36 months.

Defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR), as assessed according to RECIST v1.1.
Assessed up to approximately 36 months.
Duration of Response (DoR)
Time Frame: Assessed up to approximately 36 months.

Defined as the time from the first documented response (CR or PR) to the first documented disease progression (PD) or death from any cause, whichever occurs first.
Assessed up to approximately 36 months.
Disease Control Rate (DCR)
Time Frame: Assessed up to approximately 36 months.

Defined as the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) following treatment, as assessed according to RECIST v1.1.
Assessed up to approximately 36 months.
Time to Death or Distant Metastasis (TTDM)
Time Frame: Assessed up to approximately 36 months.

Defined as the time from randomization to the first occurrence of distant metastasis or death from any cause.
Assessed up to approximately 36 months.
Progression-Free Survival Rate at 6 Months
Time Frame: 6 months after randomization.

Kaplan-Meier estimate of the percentage of participants alive without disease progression at 6 months after randomization.
6 months after randomization.
Progression-Free Survival Rate at 12 Months
Time Frame: 12 months after randomization.

Kaplan-Meier estimate of the percentage of participants alive without disease progression at 12 months after randomization.
12 months after randomization.
Overall Survival Rate at 12 Months
Time Frame: 12 months after randomization.

Kaplan-Meier estimate of the percentage of participants alive at 12 months after randomization.
12 months after randomization.
Overall Survival Rate at 24 Months
Time Frame: 24 months after randomization.

Kaplan-Meier estimate of the percentage of participants alive at 24 months after randomization.
24 months after randomization.
Incidence of Adverse Events (AEs)
Time Frame: Assessed up to approximately 36 months.

AEs graded by CTCAE version 6.0
Assessed up to approximately 36 months.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Patients reported disease-related symptoms and HRQoL by the EORTC QLQ-C30 questionnaires
Time Frame: Assessed up to approximately 36 months.
Assessed up to approximately 36 months.
Patients reported disease-related symptoms and HRQoL by the EORTC QLQ-LC13 questionnaires
Time Frame: Assessed up to approximately 36 months.
Assessed up to approximately 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ming Chen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MA-NSCLC-II-064

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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