Clinical trial NCT05115500: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carcinoma
Solid Tumor
Lead sponsor: Second Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-11-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

1. Aged 18 years and above;
2. 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;
3. ECOG(Eastern Cooperative Oncology Group) performance is 0-3;
4. Life expectancy greater than 3 months;
5. 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；
6. Signed informed consent form；

Exclusion Criteria:

1. Current pregnancy or lactation；
2. 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);
3. Uncontrolled epilepsy, central nervous system diseases or mental illness;
4. 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;
5. Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
6. Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, uncontrolled diabetes;
7. Allergic to any of the ingredients used in the study;
8. 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;
9. Acute and chronic tuberculosis infection;
10. Other disorders with clinical significance according to the researcher's judgment.

Primary outcomes:
measure: Objective Response Rate （ORR）
timeFrame: 24 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 24 months
measure: Disease control rate (DCR)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
measure: Adverse event
timeFrame: 24 months
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jiangyin
country: China
facility: Jiangyin Peoples Hospital
city: Jinan
country: China
facility: Qilu Hospital of Shangdong University
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Kunshan
country: China
facility: The First People's Hospital of Kunshan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital of Chinese Medicine
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Suzhou
country: China
facility: Second Affiliated Hospital of Soochow University
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Weihai
country: China
facility: Weihai Municipal Hospital
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
Study officials:
References: