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

Korábbi kezelés

• Presence of other driver gene mutations with approved targeted therapies available.
• Prior treatment with HER2-targeted ADCs or HER2 TKIs.
• 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.
• Severe infection within 4 weeks prior to first dose.
• Prior or planned allogeneic bone marrow or solid organ transplantation.
• Live attenuated vaccine within 28 days prior to first dose or planned during study. Pregnancy or breastfeeding.

Más betegség

• Malignant pleural effusion, pericardial effusion, or ascites.
• Known HIV infection.
• 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.
• Known hypersensitivity to Adebrelimab, Trastuzumab Rezetecan, or any excipients.
• Known history of psychotropic substance abuse, alcohol abuse, or illicit drug use.
• Any condition that might impair the subject's ability to comply with study requirements.

Laborértékek

• Known EGFR-activating mutations or ALK fusions.
• Active hepatitis B (HBsAg positive with detectable HBV-DNA and ALT > ULN) or active hepatitis C.

Egyéb

• Mixed SCLC and NSCLC, large cell neuroendocrine carcinoma, or sarcomatoid carcinoma.

• 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).