Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer

NCT ID: NCT04508803

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-14
• Study Completion Date: 2023-02-28

Brief Summary

A number of anti-PD-1/L1 monoclonal antibodies have been approved for the treatment of various advanced tumors in the world, and many studies on anti-PD-1 /L1 monoclonal antibodies for breast cancer are also being carried out. HX008 (Taizhou Hanzhong Biomedical Co., Ltd.China) combined gemcitabine and cisplatin (GP) regimen for first-line treatment of advanced triple negative breast cancer has been shown good efficacy. On the other hand,HRD as the target of PARP inhibitor therapy in the treatment of breast cancer has a broad prospect, In HRD tumor patients, the use of PARPi can make obstacles of DNA damage repair(DDR), accumulation of DNA damage, thus promote the apoptosis of tumor cells. Several PARPi have been approved worldwide (including Olaparib, Rucaparib, Niraparib, Talazoparib, Veliparib) for the treatment of ovarian and/or breast cancer. Theoretically, PARPi and anti-PD-1 monoclonal antibody can play a synergistic mechanism. In this study, HX008 combined with Niraparib is designed to treat metastatic breast cancer patients with DDR gene (BRCA1/2, PALB2, CHEK2, ATM, ATR, BAP1, BARD1, BLM, BRIP1, CHEK1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN, PTEN, RAD50, RAD51C, RAD51D, WRN) pathogenic/suspected pathogenic germline mutation, so as to explore the possibility of more combined therapy for breast cancer to achieve better therapeutic effect.

Conditions

Treatment Efficacy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The main research

Patients diagnosed with HER2 negative metastatic breast cancer with BRCA1/2, PALB2, CHEK2 pathogenic/suspected pathogenic germline mutation are recruited.

Group Type: EXPERIMENTAL

HX008，Niraparib

Intervention Type: DRUG

Subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Niraparib orally per day.Every 3 weeks is a cycle.

Ancillary Exploration research 1

Patients diagnosed with HER2 negative metastatic breast cancer with DDR gene (include ATM、ATR、BAP1、BARD1、BLM、BRIP1、CHEK1、CDK12、FANCA、FANCC、FANCD2、FANCE、FANCF、FANCM、MRE11A、NBN、PTEN、RAD50、RAD51C、RAD51D、WRN)pathogenic/suspected pathogenic germline mutation except BRCA1/2, PALB2 and CHEK2 are recruited.

Group Type: EXPERIMENTAL

HX008，Niraparib

Intervention Type: DRUG

Subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Niraparib orally per day.Every 3 weeks is a cycle.

Ancillary Exploration research 2

Patients diagnosed with HER2 positive metastatic breast cancer with DDR gene pathogenic/suspected pathogenic germline mutation are recruited.

Group Type: EXPERIMENTAL

HX008，Niraparib，Trastuzumab

Intervention Type: DRUG

Subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day;Trastuzumab 8mg/kg in the first cycle and 6mg/kg after the first cycle intravenously once every 3 weeks; Every 3 weeks is a cycle.

Ancillary Exploration research 3

Patients diagnosed with brain metastases breast cancer with DDR gene pathogenic/suspected pathogenic germline mutation who has not undergone or progressed after brain radiotherapyare recruited.

Group Type: EXPERIMENTAL

HX008，Niraparib，Pyrrolitinib

Intervention Type: DRUG

HER-2 negative subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Neirapali orally per day. Every 3 weeks is a cycle.

Her-2 positive subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day; Pyrrolitinib is taken orally at 400mg per day; Every 3 weeks is a cycle.

Interventions

HX008，Niraparib

Subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Niraparib orally per day.Every 3 weeks is a cycle.

Intervention Type: DRUG

HX008，Niraparib

Subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Niraparib orally per day.Every 3 weeks is a cycle.

Intervention Type: DRUG

HX008，Niraparib，Trastuzumab

Subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day;Trastuzumab 8mg/kg in the first cycle and 6mg/kg after the first cycle intravenously once every 3 weeks; Every 3 weeks is a cycle.

Intervention Type: DRUG

HX008，Niraparib，Pyrrolitinib

HER-2 negative subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Neirapali orally per day. Every 3 weeks is a cycle.

Her-2 positive subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day; Pyrrolitinib is taken orally at 400mg per day; Every 3 weeks is a cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Performance Status 0-1.

2. Life expectancy longer than 3 months.

3. Histological proven unresectable recurrent or advanced breast cancer.

4. For ehe main research: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-negative breast cancer with definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2.

5. For ancillary exploration research 1: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-negative breast cancer with definite pathogenic/suspected pathogenic germline mutations in ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.

6. For ancillary exploration research 2: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-positive breast cancer with definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2, or ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.

7. For ancillary exploration research 3: Patients with histopathologically diagnosed advanced (recurrent or metastatic) breast cancer with brain and with metastases definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2, or ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.

8. Not more than 2 - line chemotherapy regimens were received in the stage of recurrence and metastasis.Platinum-based or PARP1 inhibitor treatment may be accepted, but the patient must have no disease progression during or within 8 weeks of the end of platinum-based or PARP1 inhibitor treatment at the stage of recurrence and metastasis, and relapse within 12 months after the end of neoadjuvant/adjuvant therapy.

9. Patients with hormone-receptor-positive, HER2 negative must received at least first-line endocrine therapy and progress to the stage of recurrence or metastasis, or have disease recurrence or metastasis during adjuvant endocrine therapy or within 1 year after the end of adjuvant therapy.

10. At least one extracranial measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1).

11. All patients enrolled are required to have adequate hematologic, hepatic, and renal function

12. Women of childbearing age must have a pregnancy test (serum or urine) that is negative within 7 days of enrollment, and be willing to use an appropriate method of contraception during the study and 8 weeks after the last dose of the study drug.

13. Be able to understand the study procedures and sign informed consent.

Exclusion Criteria

1. Pregnant or lactating women.

2. Treatment with an investigational product within 4 weeks before the first treatment.

3. Subjects have any active autoimmune disease, history of autoimmune disease, or history of disease or syndrome requiring systemic steroid or immunosuppressive medication.

4. Subjects had a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disorders.

5. Received chemotherapy, radiotherapy, targeted therapy and major surgery within 3 weeks before the first administration;Received endocrine therapy within 2 weeks prior to first administration.

6. Uncontrolled serious infection.

7. Patients with hypertension and uncontrolled hypertension with hypotensive drugs therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). Patients with grade I or above myocardial ischemia or myocardial infarction or arrhythmia (including QT interval ≥ 440 ms) or cardiac insufficiency.

8. Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption.

9. Patients with active viral hepatitis B or C.

10. Patients with chronic obstructive pulmonary disease (COPD), or pulmonary fibrosis.

11. Have received prior treatment with anti-PD-1/PD-L1 drugs and PARP inhibitors;

12. Patient who has a history of psychotropic substance abuse and is unable to stop or have a history of mental disorders.

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Jian Zhang,MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jian Zhang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer center

Shanghai, , China

Countries

China

Other Identifiers

CHANGEABLE

Identifier Type: -

Identifier Source: org_study_id