A Prospective Phase II Clinical Trial Evaluating the Efficacy and Safety of Adebrelimab in Combination With Trastuzumab Rezetecan for Patients With Stage III Unresectable HER2-Positive NSCLC

NCT07778745 | Not Yet Recruiting Phase 2

• 1 other identifier: NSCLC-HER2-II-001
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, open-label, multicenter phase II investigator-initiated trial. The study aims to explore the efficacy and safety of Adebrelimab plus Trastuzumab rezetecan induction therapy in patients with stage III unresectable HER2-altered non-small cell lung cancer (NSCLC). Eligible patients receive 3-4 cycles Q3W induction combination therapy. After induction, patients will receive radical surgery or concurrent chemoradiotherapy via MDT evaluation, followed by consolidation therapy and long-term survival follow-up. The primary endpoint is objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints include surgical conversion rate, major pathological response (MPR), event-free survival (EFS), overall survival (OS), and safety profiles.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of participants achieving Complete Response (CR) or Partial Response (PR) after 3-4 cycles induction therapy, assessed per RECIST v1.1 by investigators

  End of Cycle 3/Cycle 4 induction (each cycle 21 days). Surgery-eligible patients assess tumor 6-8 weeks after Cycle3 last dose; others evaluate at Cycle4 end, ±7-day imaging window.

Secondary Outcomes (5)

• Surgical Conversion Rate

  Within 6 to 8 weeks after the last induction study drug infusion (42-56 days post final induction dose)

• Major Pathological Response (MPR) Rate

  Within 4 weeks after curative lung resection (pathology report completion window)

• Event-Free Survival (EFS)

  Up to 36 months after the first dose of study treatment (3-year full survival follow-up)

• Overall Survival (OS)

  12 months, 18 months, 24 months, and 36 months after the first dose of study treatment

• Safety Profile (Treatment-Related Adverse Events)

  From the date of signed informed consent through 30 days after the last study treatment infusion; long-term safety follow-up continues up to 36 months post first dose for delayed irAEs.

Study Arms (1)

Experimental: Adebrelimab + Trastuzumab rezetecan Induction Therapy

EXPERIMENTAL

Drug: Adebrelimab; Drug: Trastuzumab rezetecan

Interventions

Adebrelimab DRUG

1200mg intravenous infusion on Day 1 of every 21-day cycle for 3-4 induction cycles; consolidation therapy after local treatment as physician discretion. Infusion duration 30-60 minutes.

Experimental: Adebrelimab + Trastuzumab rezetecan Induction Therapy

Trastuzumab rezetecan DRUG

3.2mg/kg intravenous infusion on Day 1 of every 21-day cycle for 3-4 induction cycles; fixed dose 408mg if body weight ≥85kg. First infusion over 90 mins, subsequent cycles 60 mins if well tolerated.

Experimental: Adebrelimab + Trastuzumab rezetecan Induction Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years, male or female.
• Histologically or cytologically confirmed stage III unresectable NSCLC per AJCC 9th edition, judged unresectable by institutional MDT team.
• Confirmed HER2 alteration: HER2 mutation/amplification detected by tissue NGS, or HER2 protein overexpression (IHC 2+ or 3+).
• No prior systemic anti-tumor therapy for NSCLC; prior anti-tumor Chinese herbal medicine allowed if ≥2 weeks washout before first dose.
• At least 1 measurable target lesion per RECIST v1.1.
• ECOG performance status 0 or 1.
• Able to provide tumor tissue specimen (archival ≤6 months or newly biopsied non-irradiated lesion).
• FEV1 \>1.0 L and FEV1% predicted \>40% within past 3 months.
• Adequate organ function within 7 days before first dose (no blood product/G-CSF support within 14 days):
• Hematology: WBC ≥3.0×10⁹/L, ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90g/L
• Liver: AST/ALT ≤2.5×ULN (≤5×ULN for liver metastasis), TBIL ≤1.5×ULN
• Renal: Serum Cr ≤1.5×ULN or CrCl ≥50 mL/min
• Cardiac: LVEF ≥50% by echocardiogram
• Fertile male/female participants must use effective contraception during treatment and 6 months after last dose; female participants non-lactating, negative serum HCG within 14 days pre-first dose.
• Voluntarily sign written informed consent, good compliance for follow-up.

You may not qualify if:

• Mixed small cell/large cell neuroendocrine/sarcomatoid NSCLC histology.
• Concurrent other actionable driver gene alterations (EGFR, ALK, MET, BRAF, RET etc.) besides HER2.
• Past or concurrent other malignant tumor (except fully resected cancer ≥5 years without active treatment).
• Prior thoracic radiotherapy.
• Major surgery within 28 days or minor invasive surgery within 7 days before first dose.
• HIV infection, active hepatitis B/C, organ transplant history, congenital/acquired immunodeficiency.
• Systemic immune modulators (thymosin, interferon, IL-2) within 4 weeks pre-enrollment.
• Uncontrolled severe cardiovascular disease, unstable angina or intervention-required ventricular arrhythmia within 1 month.
• Confirmed or suspected interstitial lung disease, severe baseline pulmonary dysfunction interfering with lung toxicity monitoring.
• Active uncontrolled ≥2 grade infection within 2 weeks before enrollment.
• Active tuberculosis under treatment.
• Known hypersensitivity to any component of study drugs or other monoclonal antibodies/fusion proteins.
• Any condition judged by investigator to compromise participant safety or trial compliance.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Central Study Contacts

Meng Wang Meng Wang

CONTACT

18622221623; 18622221623@pm.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 21, 2026
• Study Start: August 20, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2029
• Last Updated: August 21, 2026

Record last verified: 2026-08