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

Conditions

• Treatment Efficacy

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• HX008，Niraparib — 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.
• HX008，Niraparib — 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.
• HX008，Niraparib，Trastuzumab — 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.
• HX008，Niraparib，Pyrrolitinib — 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.

Study Details

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.

Key Dates

Start date

Sep 14, 2020

Status verified

Jun 2020

Primary completion

Aug 20, 2022

Completion

Feb 28, 2023

Study Design

Enrollment

37 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: The main research
  Patients diagnosed with HER2 negative metastatic breast cancer with BRCA1/2, PALB2, CHEK2 pathogenic/suspected pathogenic germline mutation are recruited.
• Experimental: 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.
• Experimental: Ancillary Exploration research 2
  Patients diagnosed with HER2 positive metastatic breast cancer with DDR gene pathogenic/suspected pathogenic germline mutation are recruited.
• Experimental: 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.

Primary Outcome Measure

Overall Response Rate (ORR) [ Time Frame: Up to approximately 12 weeks ]