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

NCT07489703 | Not Yet Recruiting Phase 2

• 1 other identifier: MA-NSCLC-II-062
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

NSCLC; HER2

Outcome Measures

Primary Outcomes (1)

• PFS

  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.

  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 Outcomes (6)

• 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.

Study Arms (2)

Cohort 1

EXPERIMENTAL

Cohort 1 includes patients who failed standard first-line therapy, patients receive treatment with SHR-A1811 and AK112 until disease progression or meeting other criteria for treatment discontinuation, whichever occurs first.

Drug: SHR-A1811 plus AK112

Cohort 2

EXPERIMENTAL

Cohort 2 includes treatment-naïve patients. Patients receive treatment with SHR-A1811 and AK112 until disease progression or meeting other criteria for treatment discontinuation, whichever occurs first.

Drug: SHR-A1811 plus AK112

Interventions

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.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Zhang, Professor

CONTACT

+86-20-87343289; zhangli@sysucc.org.cn

Yan Huang, Professor

CONTACT

huangyan@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 24, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share