NSCLC
Conditions
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.
Interventions
DRUGAdebrelimab
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.
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.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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. | Proportion of participants achieving Complete Response (CR) or Partial Response (PR) after 3-4 cycles induction therapy, assessed per RECIST v1.1 by investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | Up to 36 months after the first dose of study treatment (3-year full survival follow-up) | Time from first study drug dose to disease progression, local recurrence, distant metastasis, or death from any cause |
| Overall Survival (OS) | 12 months, 18 months, 24 months, and 36 months after the first dose of study treatment | OS defined as time from first dose to all-cause death; survival rate calculated at fixed time points |
| 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. | Incidence and grade of all adverse events, ≥3 grade AEs, serious adverse events (SAE), immune-related AEs, interstitial lung disease graded per NCI CTCAE v6.0 |
| Major Pathological Response (MPR) Rate | Within 4 weeks after curative lung resection (pathology report completion window) | Proportion of surgical patients with ≤10% viable tumor cells in resected primary tumor specimen (central blinded pathology review) |
| Surgical Conversion Rate | Within 6 to 8 weeks after the last induction study drug infusion (42-56 days post final induction dose) | Percentage of subjects receiving R0 radical pulmonary resection after MDT re-evaluation post induction |
Contacts
CONTACTMeng Wang Meng Wang
Outcome results
None listed