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)

Solid Tumor Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05115500
• Other study ID #: JD-LK-2021-121-01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: April 30, 2025

Study information

• Verified date: November 2021
• Source: Second Affiliated Hospital of Soochow University
• Contact: Liyuan Zhang, doctor
• Phone: 0512-67784829
• Email: zhangliyuan126[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: April 30, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Neoplasms
• Solid Tumor

Intervention

Drug:
• ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2
RC48-ADC combined with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF and IL-2

Locations

Country	Name	City	State
China	The First Bethune Hospital of Jilin University	Changchun
China	The First People's Hospital of Changzhou	Changzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangyin Peoples Hospital	Jiangyin
China	Qilu Hospital of Shangdong University	Jinan
China	Shandong Cancer Hospital	Jinan
China	The First People's Hospital of Kunshan	Kunshan
China	Jiangsu Cancer Hospital	Nanjing
China	Jiangsu Province Hospital	Nanjing
China	Jiangsu Province Hospital of Chinese Medicine	Nanjing
China	Nanjing Drum Tower Hospital	Nanjing
China	Affiliated Hospital of Nantong University	Nantong
China	The First Hospital of China Medical University	Shenyang
China	Second Affiliated Hospital of Soochow University	Suzhou
China	Suzhou Municipal Hospital	Suzhou
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Weihai Municipal Hospital	Weihai
China	Affiliated Hospital of Jiangnan University	Wuxi
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall survival (OS)	OS was defined as the time from the first administration of study treatment to death from any cause.	24 months
Secondary	Adverse event	rate of adverse events	24 months