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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: SHR-A1811 plus AK112

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Zhang, Professor; Phone Number: +86-20-87343289; Email: zhangli@sysucc.org.cn
• Study Contact Backup: Name: Yan Huang, Professor; Email: huangyan@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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; Patients will receive the combination of SHR-A1811 and AK112 until disease progression or until other predefined discontinuation criteria are met, whichever occurs first.
Experimental: Cohort 2; 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; Patients will receive the combination of SHR-A1811 and AK112 until disease progression or until other predefined discontinuation criteria are met, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR	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.	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	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.	From first study treatment to disease progression or initiation of new anti-tumor therapy, assessed up to approximately 36 months.
OS	Overall survival (OS), defined as the time from first study treatment to death from any cause.	From date of first study treatment to date of death from any cause, assessed up to approximately 36 months.
Adverse Events	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.	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	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.	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	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.	From first dose of study treatment through 90 days after the last dose or initiation of new anti-tumor therapy, whichever occurs first.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Li Zhang, Professor, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; HER2
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: MA-NSCLC-II-062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing was not included in the informed consent form approved by the ethics committee. Therefore, sharing individual participant data would violate the ethical agreements made with study participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No