Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, HER2
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.
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
DRUGSHR-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.
Sponsors
Sun Yat-sen University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| ORR | 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. |
| OS | 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. |
| 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. | 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. |
| 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. | 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. |
| Treatment-Related Adverse Events | 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. |
Contacts
CONTACTLi Zhang, Professor
CONTACTYan Huang, Professor
PRINCIPAL_INVESTIGATORLi Zhang, Professor
Sun Yat-sen University
Outcome results
None listed