A Phase II Trial of Camrelizumab in Combination With Apatinib and Eribulin in Patients With Advanced TNBC

• ClinicalTrials.gov Identifier: NCT04303741
• Recruitment Status: Active, not recruiting
• First Posted: March 11, 2020
• Last Update Posted: April 12, 2023
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Information provided by (Responsible Party): Jieqiong Liu, M.D., Ph.D., Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Tracking Information

• First Submitted Date: March 7, 2020
• First Posted Date: March 11, 2020
• Last Update Posted Date: April 12, 2023
• Actual Study Start Date: March 25, 2020
• Actual Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 9, 2020)

Overall response rate (ORR) [ Time Frame: from the first drug administration up to the first occurrence of progression or death (up to 24 months) ]

The propotion of subjects with CR or PR.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 9, 2020)

• Incidence of Treatment-Emergent Adverse Events [ Time Frame: from the first drug administration to within 90 days for the last dose ]
  Adverse events/serious adverse events
• Disease Control Rate (DCR) [ Time Frame: from the first drug administration up to the first occurrence of progression or death(up to 24 months) ]
  The propotion of subjects with CR, PR, or SD.
• DOR [ Time Frame: from the first drug administration up to the first occurrence of progression or death(up to 24 months) ]
  Duration of response
• PFS [ Time Frame: from the first drug administration up to the first occurrence of progression or death (up to 24 months) ]
  Progression-Free-Survival
• One year-OS rate [ Time Frame: 12 months after the first drug administration ]
  One year-Overall survival rate
• Clinical benefit rate (CBR) [ Time Frame: from the first drug administration up to the first occurrence of progression or death(up to 24 months) ]
  The propotion of subjects with CR, PR, or SD for >=6 months during the study.
• TTR [ Time Frame: from the first drug administration up to one year ]
  Time to response
• Frequencies of Biomarkers [ Time Frame: pre-treatment, up to 24 months ]
  Biomarkers (including tumor/stromal PD-L1, stromal PD-1, tumor-infiltrating lymphocytes and tumor-infiltrating B cells, eg)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II Trial of Camrelizumab in Combination With Apatinib and Eribulin in Patients With Advanced TNBC
• Official Title: An Open-labeled, Single-arm, Investigator-initiated Phase II Trial of Camrelizumab (Anti-PD-1 Antibody) in Combination With Apatinib and Eribulin in Patients With Advanced Triple-Negative Breast Cancer
• Brief Summary: This is a phase II, open-labeled, multi-centered,single-arm, Investigator-initiated clinical trial of camrelizumab (an anti-PD-1 antibody) in combination with apatinib (a VEGFR2 TKI) and eribulin mesylate in patients with advanced triple-negative breast cancer. We will enroll 46 subjects (Simons two stage design). This study aims to evaluate the efficacy and safety of camrelizumab combined with apatinib and eribulin in the treatment of advanced TNBC.
• Detailed Description: This a phase II, open-labeled, multi-centered, single-arm, investigator-initiated clinical trial to assess the efficacy and safety of camrelizumab combination with apatinib and eribulin in female patients age of 18 to 70 with advanced TNBC, and previously treated with at least one line of systemic therapy in the advanced setting. Prior therapy (adjuvant/neoadjuvant/advanced) must have included an anthracycline and a taxane. The number of patients to be included is 46 patients (Simons two stage design). The primary objective is to assess the overall response rate (ORR). All enrolled patients will be treated with camrelizumab 200mg (iv. 3mg/kg for patient whose weight is below 50kg) on day 1 of each 21-day cycle, and apatinib 250mg daily (po, d1-d21), in combination with eribulin mesylate at 1.4 mg/m2 (iv.) on day 1 and day 8 of every 21-day cycle.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Camrelizumab
  Camrelizumab 200mg (3mg/kg for patient whose weight is below 50kg) will be administered as an intravenous infusion over 30 minutes every three weeks until unacceptable toxic effects or disease progression or other termination criteria appeared. Patients received up to two years of treatment.
• Drug: Apatinib
  Apatinib 250mg will be administered daily until unacceptable toxic effects or disease progression or other termination criteria appeared. Patients received up to two years of treatment.
• Drug: Eribulin
  Eribulin Mesylate will be administered as a 1.4 mg/m2 intravenous (IV) injection over 2 to 5 minutes on day 1 and day 8 of each 21-day cycle until unacceptable toxic effects or disease progression or other termination criteria appeared. Patients received up to two years of treatment.
  Other Name: Eribulin Mesylate

Study Arms

Experimental: Camrelizumab +Apatinib+Eribulin

Camrelizumab 200mg(3mg/kg for patient whose weight is below 50kg) iv Q3W combination with Apatinib 250mg, po, daily (d1-d21)and Eribulin1.4mg/m2 iv d1, d8 Q3W

Interventions:

• Drug: Camrelizumab
• Drug: Apatinib
• Drug: Eribulin

• Publications *: Liu J, Wang Y, Tian Z, Lin Y, Li H, Zhu Z, Liu Q, Su S, Zeng Y, Jia W, Yang Y, Xu S, Yao H, Jiang W, Song E. Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022 May 31;13(1):3011. doi: 10.1038/s41467-022-30569-0.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 9, 2020): 46
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2023
• Actual Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The patients sign the written informed consent.
2. Women aged 18-70.
3. The pathologic diagnosis of unresectable recurrent or metastatic triple-negative breast cancer ［ER-negative(IHC<1%), PR-negative(IHC<1%), HER2-negative（IHC-/+ or IHC++ and FISH/CISH-）］. Patients with at least one measuring lesion that was conformed to RECIST v1.1 standard.
4. Prior therapy (adjuvant/neoadjuvant/advanced) must have included an anthracycline and a taxane in any combination or order and either in the early or metastatic disease setting unless contraindicated for a given patient.
5. The patient can swallow pills.
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
7. With a life expectancy of at least 12 weeks.

8. The results of patient's blood tests are as follows:

   • Hb≥90g/L; • Plt≥100^9/L; • Serum albumin ≥3g/dL;• Neutrophils≥1.5^9/L; TSH≤ normal upper limit (ULN);• ALT and AST ≤1.5 ULN (liver metastases ≤3 ULN); • TBIL ≤ULN (total bilirubin ≤1.5 ULN in Gilbert's syndrome or liver metastasis subjects);• ALT and AST ≤1.5 ULN (liver metastases ≤3 ULN);• AKP≤ 2.5 ULN; • Renal function within 7 days before the first administration: serum creatinine ≤1.5 ULN or creatinine clearance ≥60mL/min

9. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 6 months after the last dose of study treatment.

Exclusion Criteria:

1. The subjects had a central nervous system metastases with clinical symptoms.
2. Other clinical trials of drugs were used in the first four weeks before the first dose.
3. Subjects with severe allergic reactions to other monoclonal antibodies.
4. Received other anti-tumor treatments within 28 days before the first dose.
5. A heart condition or disease that is not well controlled.
6. Subjects with treatment history of anti-angiogenesis drugs, or immunotherapy (previous use of anti-PD-1/PD-L1 antibodies was allowed) or eribulin.
7. The subjects had any history of autoimmune disease or any use of systemic glucocorticoid or immunosuppressive medications.
8. Subjects had history of hypertension and poor control with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
9. Urine routine indicated that urine protein ≥ ++, or the 24-hour urine protein quantity ≥ 1.0g.
10. Hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.).
11. Congenital or acquired immune deficiency (such as HIV infection);
12. Receive live vaccine within 4 weeks before or during the study period;
13. Patients who are allergic to or contraindicated to the experimental drugs.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04303741
• Other Study ID Numbers: Immuno2020-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jieqiong Liu, M.D., Ph.D., Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jieqiong Liu; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

• PRS Account: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Verification Date: April 2023