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NCT Number: NCT07489703

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

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.

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

SHR-A1811 plus AK112

Drug

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 outcomes

  1. 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

  1. 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.

    Duration of response (DOR), defined as the time from the first documented objective response (complete response or partial response) to the first documented disease progression or death from any cause prior to progression, whichever occurs first. Objective response is assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  2. ORR

    Time frame: From first study treatment to disease progression or initiation of new anti-tumor therapy, assessed up to approximately 36 months.

    Objective response rate (ORR), defined as the proportion of participants achieving a best overall response of complete response (CR) or partial response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  3. OS

    Time frame: From date of first study treatment to date of death from any cause, assessed up to approximately 36 months.

    Overall survival (OS), defined as the time from first study treatment to death from any cause.

  4. 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.

    Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Relationship to study treatment (SHR-A1811 and/or AK112) is assessed by the investigator.

  5. 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.

    Incidence of serious adverse events (SAEs), regardless of causality, as defined in the study protocol. SAEs include events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability/incapacity, are congenital anomalies/birth defects, or are other medically important conditions.

  6. 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.

    Incidence and severity of treatment-related adverse events (TRAEs), defined as adverse events assessed by the investigator as having a reasonable possibility of causal relationship to SHR-A1811 and/or AK112. Severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Study contacts

Contact information is provided by the study sponsor or research team.

Li Zhang, Professor

CONTACT

[email protected]

+86-20-87343289

Yan Huang, Professor

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Registry information

Official study 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

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Mar 24, 2026
Registry last updated
Mar 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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