SHR-A1811 + AK112 in HER2-Altered Advanced/Metastatic NSCLC

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

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.

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.

Inclusion Criteria:

1. Signed ICF.
2. Age 18-75.
3. ECOG PS 0-1.
4. Life expectancy ≥3 months.
5. Histologically/cytologically confirmed locally advanced or metastatic/recurrent NSCLC, not eligible for curative surgery or definitive chemoradiotherapy.
6. Cohort 1: Failed prior first-line systemic therapy, with HER2 amplification or overexpression . Cohort 2: No prior systemic therapy, with HER2 amplification/overexpression .
7. ≥1 measurable lesion per RECIST 1.1.
8. Adequate organ and bone marrow function.
9. Use of effective contraception.

Exclusion Criteria:

1. History of ILD, pneumonitis requiring steroids, or active non-infectious pneumonitis.
2. Arterial/venous thrombotic event within 6 months.
3. Significant cardiovascular disease.
4. Active autoimmune disease requiring systemic treatment.
5. Use of systemic immunosuppressants within 2 weeks prior.
6. Symptomatic pleural/pericardial/ascitic effusion requiring drainage.
7. Symptomatic, progressive, or diffusely spread CNS metastases.