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

NCT07836543 | Not Yet Recruiting Phase 2

• 1 other identifier: MA-NSCLC-II-064
• Study Type: interventional
• Target: 105
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Defined as the time from randomization to disease progression or death from any cause, whichever occurs first.

  Assessed up to approximately 36 months.

Secondary Outcomes (10)

• Overall Survival (OS)

  Assessed up to approximately 60 months.

• Objective Response Rate (ORR)

  Assessed up to approximately 36 months.

• Duration of Response (DoR)

  Assessed up to approximately 36 months.

• Disease Control Rate (DCR)

  Assessed up to approximately 36 months.

• Time to Death or Distant Metastasis (TTDM)

  Assessed up to approximately 36 months.

Other Outcomes (2)

• Patients reported disease-related symptoms and HRQoL by the EORTC QLQ-C30 questionnaires

  Assessed up to approximately 36 months.

• Patients reported disease-related symptoms and HRQoL by the EORTC QLQ-LC13 questionnaires

  Assessed up to approximately 36 months.

Study Arms (3)

Arm A (Combination Therapy)

EXPERIMENTAL

Drug: Trastuzumab Rezetecan + Adebrelimab

Drug: Trastuzumab Rezetecan (SHR-A1811) + Adebrelimab

Arm B (Targeted Monotherapy)

EXPERIMENTAL

Drug: Trastuzumab Rezetecan

Drug: Trastuzumab Rezetecan (SHR-A1811)

Arm C (Immunotherapy Monotherapy)

EXPERIMENTAL

Drug: Adebrelimab

Drug: Adebrelimab

Interventions

Trastuzumab Rezetecan (SHR-A1811) DRUG

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.

Arm B (Targeted Monotherapy)

Adebrelimab DRUG

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.

Arm C (Immunotherapy Monotherapy)

Trastuzumab Rezetecan (SHR-A1811) + Adebrelimab DRUG

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.

Arm A (Combination Therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• ECOG performance status 0-1.
• Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC).
• Radiologically confirmed unresectable Stage III NSCLC per AJCC 9th edition.
• Pathologically confirmed HER2 mutation or HER2 overexpression (IHC 2+ or 3+).
• Life expectancy ≥3 months.
• 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.
• Total radiotherapy dose 60 Gy ± 10% (54-66 Gy) using IMRT (preferred) or 3D-CRT, with acceptable dosimetric constraints.
• Adequate organ and bone marrow function.
• 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.
• Signed informed consent form (ICF).

You may not qualify if:

• Known EGFR-activating mutations or ALK fusions.
• Presence of other driver gene mutations with approved targeted therapies available.
• Mixed SCLC and NSCLC, large cell neuroendocrine carcinoma, or sarcomatoid carcinoma.
• Prior treatment with HER2-targeted ADCs or HER2 TKIs.
• Malignant pleural effusion, pericardial effusion, or ascites.
• Participation in another clinical trial within 4 weeks or 5 half-lives prior to first dose.
• Systemic immunosuppressive therapy within 2 weeks prior to first dose.
• Known HIV infection.
• Active hepatitis B (HBsAg positive with detectable HBV-DNA and ALT \> ULN) or active hepatitis C.
• Active autoimmune disease requiring systemic treatment.
• 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.
• 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.
• Significant cardiovascular disease.
• Severe infection within 4 weeks prior to first dose.
• Prior or planned allogeneic bone marrow or solid organ transplantation.

Sponsors & Collaborators

• Ming Chen: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Ming Chen, MD

CONTACT

+86 020-87345647; chenming@sysucc.org.cn

Chenfei Wu, MD

CONTACT

+86 020-87345647; wucf@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor and Chief Physician

Model Details: Patients will be randomized in a 1:1:1 ratio to three parallel arms: Arm A (Trastuzumab Rezetecan + Adebrelimab), Arm B (Trastuzumab Rezetecan monotherapy), and Arm C (Adebrelimab monotherapy).

Study Record Dates

• First Submitted: September 13, 2026
• First Posted: September 23, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: September 23, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share