A Phase II Clinical Trial to Evaluate the Efficacy and Safety of SHR-A1811 Combined With Ivonescimab (AK112) in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With HER2 Abnormalities
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 30
- Primary Endpoint
- PFS
Overview
Brief Summary
This is a phase II, open-label, single-arm study evaluating the efficacy and safety of SHR-A1811 (a HER2-targeted ADC) combined with AK112 (a PD-1/VEGF bispecific antibody) in patients with HER2-amplified or overexpressed locally advanced or metastatic NSCLC.
Detailed Description
The study consists of two cohorts: Cohort 1 includes patients who failed standard first-line therapy; Cohort 2 includes treatment-naïve patients. Patients will receive treatment with SHR-A1811 and AK112 until disease progression or meeting other criteria for treatment discontinuation, whichever occurs first.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed ICF.
- •Life expectancy ≥3 months.
- •Histologically/cytologically confirmed locally advanced or metastatic/recurrent NSCLC, not eligible for curative surgery or definitive chemoradiotherapy.
- •Cohort 1: Failed prior first-line systemic therapy, with HER2 amplification or overexpression . Cohort 2: No prior systemic therapy, with HER2 amplification/overexpression .
- •≥1 measurable lesion per RECIST 1.
- •Adequate organ and bone marrow function.
- •Use of effective contraception.
Exclusion Criteria
- •History of ILD, pneumonitis requiring steroids, or active non-infectious pneumonitis.
- •Arterial/venous thrombotic event within 6 months.
- •Significant cardiovascular disease.
- •Active autoimmune disease requiring systemic treatment.
- •Use of systemic immunosuppressants within 2 weeks prior.
- •Symptomatic pleural/pericardial/ascitic effusion requiring drainage.
- •Symptomatic, progressive, or diffusely spread CNS metastases.
Outcomes
Primary Outcomes
PFS
Time Frame: From date of first study treatment to the date of first documented disease progression or date of death from any cause, whichever occurs first, assessed up to approximately 36 months.
Progression-free survival (PFS), defined as the time from first study treatment to disease progression or death from any cause, whichever occurs first. Disease progression is assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Secondary Outcomes
- DOR(From the date of first documented objective response to the date of first documented disease progression or death from any cause prior to progression, whichever occurs first, assessed up to approximately 36 months.)
- ORR(From first study treatment to disease progression or initiation of new anti-tumor therapy, assessed up to approximately 36 months.)
- OS(From date of first study treatment to date of death from any cause, assessed up to approximately 36 months.)
- Adverse Events(From signing of informed consent through 90 days after the last dose of study treatment or initiation of new anti-tumor therapy, whichever occurs first.)
- Serious Adverse Events(From signing of informed consent through 90 days after the last dose of study treatment or initiation of new anti-tumor therapy, whichever occurs first.)
- Treatment-Related Adverse Events(From first dose of study treatment through 90 days after the last dose or initiation of new anti-tumor therapy, whichever occurs first.)
Investigators
Li Zhang, MD
Chief Physician
Sun Yat-sen University