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

Official title

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

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.

Interventions

• Drug SHR-A1811 plus AK112
  Patients will receive the combination of SHR-A1811 and AK112 until disease progression or until other predefined discontinuation criteria are met, whichever occurs first.

Primary outcome measures

• 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.]

Secondary outcome measures (6)

• DOR [Time frame: 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 [Time frame: From first study treatment to disease progression or initiation of new anti-tumor therapy, assessed up to approximately 36 months.]
• OS [Time frame: From date of first study treatment to date of death from any cause, assessed up to approximately 36 months.]
• Adverse Events [Time frame: 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 [Time frame: 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 [Time frame: From first dose of study treatment through 90 days after the last dose or initiation of new anti-tumor therapy, whichever occurs first.]

Eligibility criteria

Inclusion criteria

• Signed ICF.
• Age 18-75.
• ECOG PS 0-1.
• 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 1.1.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07489703 · MA-NSCLC-II-062

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗