A Study of SHR-A1811 Combined With Adebelimumab as Neoadjuvant Therapy for Resectable HER2-Altered Non-Small Cell Lung Cancer

A Single-Arm Phase II Clinical Study of SHR-A1811 Combined With Adebelimumab as Neoadjuvant Therapy for Resectable HER2-Altered Non-Small Cell Lung Cancer

This is a prospective, single-arm, multi-center Phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant therapy with SHR-A1811 in combination with Adebelimumab in patients with resectable, early-stage non-small cell lung cancer (NSCLC) harboring HER2 alterations.

Inclusion Criteria:

1. Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);
2. Aged 18-75 years, male or female;
3. Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (AJCC staging system, version 9) NSCLC
4. HER2 alterations identified by histological specimens;
5. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1 (RECIST v1.1);
6. ECOG score 0-1;
7. No contraindications to immunotherapy;
8. Adequate organ function:
9. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study;
10. Pulmonary function being able to withstand the planned surgery evaluated by surgeons;
11. Women of childbearing potential must undergo a serum pregnancy test within 1 week prior to the first dose and the result must be negative. Female patients of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug

Exclusion Criteria:

1. Known EGFR sensitizing mutations or ALK fusions.
2. Malignant pleural effusion. Drainable effusions during screening require thoracentesis to rule out malignancy.
3. Prior anticancer therapy (radiotherapy, chemotherapy, immunotherapy), except curatively treated NSCLC with ≥5 years recurrence-free. Anticancer Chinese herbal medicine is allowed if stopped ≥2 weeks prior.
4. Active or history of autoimmune diseases (e.g., uveitis, hepatitis, vasculitis, thyroiditis). Exceptions include: resolved childhood asthma, vitiligo, psoriasis, or alopecia without systemic treatment. Patients requiring bronchodilators are excluded.
5. Immunodeficiency (e.g., HIV), active Hepatitis B (HBsAg+ & HBV DNA ≥500 IU/mL), or active Hepatitis C (HCV Ab+ & detectable HCV RNA). Resolved HBV infection (anti-HBc+, HBsAg-) is allowed.
6. Uncontrolled third-space fluid accumulation requiring repeated drainage.
7. Significant proteinuria (urine protein ≥++ and 24-hour protein ≥1.0 g) or severe hepatic/renal impairment.
8. Systemic corticosteroids (>10 mg/day prednisone equivalent) or immunosuppressants within 14 days prior to first dose. Inhaled/topical steroids or physiologic replacement doses are permitted.
9. Antitumor vaccines or immunostimulatory agents within 1 month prior to first dose.
10. Systemic immunosuppressive therapy within 2 weeks prior to first dose or anticipated need during the study. Short-term, low-dose use may be permitted after Medical Monitor approval.
11. Concurrent participation in another interventional clinical trial or prior interventional drug within 4 weeks (or 5 half-lives). Non-interventional study participation is allowed.
12. Known or suspected interstitial lung disease, or other significant pulmonary conditions that may interfere with drug-related pulmonary toxicity evaluation.
13. Severe cardiovascular disease, including: clinically significant arrhythmias; QTc ≥450 ms (male) or ≥470 ms (female); NYHA Class ≥III heart failure; or LVEF <50%.
14. Severe infection within 4 weeks prior to first dose, or active infection requiring therapeutic antibiotics within 2 weeks prior (prophylactic antibiotics allowed).
15. Active tuberculosis within 1 year prior to first dose.
16. Major surgery within 28 days prior to first dose.
17. History of allogeneic organ or stem cell transplantation.
18. Pregnancy, lactation, or unwillingness to use effective contraception.
19. Known allergy or hypersensitivity to SHR-A1811/Adebelimumab or their excipients.
20. History of psychoactive drug abuse, alcohol abuse, or drug addiction. 21 Any other condition that may compromise patient safety or study compliance, per investigator's judgment.