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)

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)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoma; Solid Tumor
• Intervention / Treatment: Drug: ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liyuan Zhang, Doctor; Phone Number: 0512-67784829; Email: zhangliyuan126@126.com

Study Locations

• China
  • Changchun, China
    • The First Bethune Hospital of Jilin University
    • Contact: Xin Jiang
  • Changzhou, China
    • The First People's Hospital of Changzhou
    • Contact: Wendong Gu
  • Harbin, China
    • Harbin Medical University Cancer Hospital
    • Contact: Lili Yu
  • Jiangyin, China
    • Jiangyin Peoples Hospital
    • Contact: Jian Wang
  • Jinan, China
    • Shandong Cancer Hospital
    • Contact: Dali Han
  • Jinan, China
    • Qilu Hospital of Shangdong University
    • Contact: Bingxu Tan
  • Kunshan, China
    • The First People's Hospital of Kunshan
    • Contact: Minbin Chen
  • Nanjing, China
    • Jiangsu Province Hospital
    • Contact: Yuandong Cao
  • Nanjing, China
    • Nanjing Drum Tower Hospital
    • Contact: Jing Yan
  • Nanjing, China
    • Jiangsu Cancer Hospital
    • Contact: Li Yin
  • Nanjing, China
    • Jiangsu Province Hospital of Chinese Medicine
    • Contact: Dahai Yu
  • Nantong, China
    • Affiliated Hospital of Nantong University
    • Contact: Xiancheng Liu
  • Shenyang, China
    • The First Hospital of China Medical University
    • Contact: Qiao Qiao
  • Suzhou, China
    • Second Affiliated Hospital of Soochow University
    • Contact: Liyuan zhang
  • Suzhou, China
    • The First Affiliated Hospital of Soochow University
    • Contact: songbing Qin
  • Suzhou, China
    • Suzhou Municipal Hospital
    • Contact: Jundong Zhou
  • Weihai, China
    • Weihai Municipal Hospital
    • Contact: Fujun Yang
  • Wuxi, China
    • Affiliated Hospital of Jiangnan University
    • Contact: Ke Gu
  • Xuzhou, China
    • The Affiliated Hospital of Xuzhou Medical University
    • Contact: Jianshe Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADC Combined With Radiotherapy, PD-1/PD-L1 Sequential GM-CSF and IL-2	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JD-LK-2021-121-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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