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.
This is a randomized, open-label, multi-center phase II study evaluating the efficacy and safety of consolidation therapy with Trastuzumab Rezetecan combined with Adebrelimab versus Trastuzumab Rezetecan monotherapy versus Adebrelimab monotherapy in patients with unresectable stage III NSCLC harboring HER2 alterations (mutation or overexpression) who have not progressed after definitive concurrent or sequential chemoradiotherapy. Eligible patients will be randomized in a 1:1:1 ratio to receive either combination therapy, SHR-A1811 alone, or Adebrelimab alone for up to 12 months. The primary endpoint is progression-free survival (PFS) per RECIST v1.1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
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.
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.
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.
Progression-Free Survival (PFS)
Defined as the time from randomization to disease progression or death from any cause, whichever occurs first.
Time frame: Assessed up to approximately 36 months.
Overall Survival (OS)
Defined as the time from randomization to death from any cause.
Time frame: Assessed up to approximately 60 months.
Objective Response Rate (ORR)
Defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR), as assessed according to RECIST v1.1.
Time frame: Assessed up to approximately 36 months.
Duration of Response (DoR)
Defined as the time from the first documented response (CR or PR) to the first documented disease progression (PD) or death from any cause, whichever occurs first.
Time frame: Assessed up to approximately 36 months.
Disease Control Rate (DCR)
Defined as the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) following treatment, as assessed according to RECIST v1.1.
Time frame: Assessed up to approximately 36 months.
Time to Death or Distant Metastasis (TTDM)
Defined as the time from randomization to the first occurrence of distant metastasis or death from any cause.
Time frame: Assessed up to approximately 36 months.
Progression-Free Survival Rate at 6 Months
Kaplan-Meier estimate of the percentage of participants alive without disease progression at 6 months after randomization.
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Time frame: 6 months after randomization.
Progression-Free Survival Rate at 12 Months
Kaplan-Meier estimate of the percentage of participants alive without disease progression at 12 months after randomization.
Time frame: 12 months after randomization.
Overall Survival Rate at 12 Months
Kaplan-Meier estimate of the percentage of participants alive at 12 months after randomization.
Time frame: 12 months after randomization.
Overall Survival Rate at 24 Months
Kaplan-Meier estimate of the percentage of participants alive at 24 months after randomization.
Time frame: 24 months after randomization.
Incidence of Adverse Events (AEs)
AEs graded by CTCAE version 6.0
Time frame: Assessed up to approximately 36 months.