ADC Combined With Hypofractionated Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2 for Treatment of HER-2 Positive Advanced Solid Tumors(PRaG3.0)

Study Overview
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Brief Summary
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This is an open-label, single-arm, Phase II investigator-initiated trial of antibody-drug conjugate combined with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF and IL-2 for treatment of advanced refractory solid tumors with HER-2 positive

Official Title
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Antibody-Drug Conjugate Combined With Hypofractionated Radiotherapy, PD-1/PD-L1 Inhibitor Sequential GM-CSF and IL-2 for the Treatment Advanced Refractory Solid Tumors With HER-2 Positive(PRaG3.0)

Conditions
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Carcinoma, Solid Tumor

Intervention / Treatment
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* Drug: ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and above; Diagnosed with histologically or cytologically-confirmed, HER2-positive(IHC 1+, 2+ or 3+), standard treatment is ineffective (disease progresses after treatment) or locally advanced or metastatic malignant solid tumor patients who cannot tolerate standard therapy, cannot receive or do not have standard therapy; ECOG(Eastern Cooperative Oncology Group) performance is 0-3; Life expectancy greater than 3 months; T lymphocyte absolute value ≥0.5 upper limit of normal (ULN), absolute neutrophil count(ANC)≥1.0 x 10(9)/L；serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤3.0*ULN, or AST and ALT≤5*ULN with hepatic metastasis; Total serum creatinine ≤1.5*ULN； Signed informed consent form； Exclusion Criteria: Current pregnancy or lactation； History of other malignant tumors within 5 years prior to dose administration, expect for：malignancies that can be cured after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer); Uncontrolled epilepsy, central nervous system diseases or mental illness; Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or greater than or equal to Class 2 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction unstable angina, or acute coronary syndrome within 6 months prior to enrollment in the study; Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation; Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, uncontrolled diabetes; Allergic to any of the ingredients used in the study; A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency disease, or a history of organ transplantation, or other immune-related disease requiring long-term oral hormone therapy; Acute and chronic tuberculosis infection; Other disorders with clinical significance according to the researcher's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2<br> | Drug: ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2<br>* RC48-ADC combined with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF and IL-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate （ORR） | Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the time from the first administration of study treatment to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first. | 24 months | 
| Disease control rate (DCR) | DCR was defined as the percentage of participants with a complete response (CR), partial response (PR), or stable disease (SD) | 24 months | 
| Overall survival (OS) | OS was defined as the time from the first administration of study treatment to death from any cause. | 24 months | 
| Adverse event | rate of adverse events | 24 months |