A Study of SHR-1210 in Combination With Apatinib or Chemotherapy in Subjects With Advanced PLC or BTC

• ClinicalTrials.gov Identifier: NCT03092895
• Recruitment Status: Completed
• First Posted: March 28, 2017
• Last Update Posted: February 8, 2023
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: March 15, 2017
• First Posted Date: March 28, 2017
• Last Update Posted Date: February 8, 2023
• Actual Study Start Date: April 27, 2017
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2017)

The safety and tolerability [ Time Frame: Up to approximately 2years ]

The incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 22, 2017)

• Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
  Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Duration of Response (DoR) [ Time Frame: Up to approximately 2 years ]
  Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Disease Control Rate (DCR) [ Time Frame: Up to approximately 6 months2 years ]
  Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Time to Progression (TTP) [ Time Frame: Up to approximately 2 years ]
  Time to Progression (TTP) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Overall Survival [ Time Frame: Up to approximately 2 years ]
  Overal Survial will be calculated based on Kaplan-Meier estimates

• 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 Study of SHR-1210 in Combination With Apatinib or Chemotherapy in Subjects With Advanced PLC or BTC
• Official Title: A Phase 2 Study of SHR-1210 (PD-1 Antibody) in Combination With Apatinib or Chemotherapy (FOLFOX4 or GEMOX) in Subjects With Advanced Primary Liver Cancer（PLC）or Biliary Tract Carcinoma (BTC)
• Brief Summary: This an open-label，Non-Randominzed Phase 2 study to evaluate the Safety and Tolerability of SHR-1210 in combination with Apatinib or chemotherapy (FOLFOX4 or GEMOX regimen) in subjects with Advanced PLC.or BTC Participants with advanced PLC who failed or intolerable to prior systemic therapy will be treated with SHR-1210 plus Apatinib; Participants with advanced PLC or BTC who have never received prior systemic therapy will be treated with SHR-1210 plus FOLFOX4 or GEMOX regimen.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Primary Liver Cancer
• Advanced Biliary Tract Carcinoma

Intervention

• Biological: SHR-1210
  Subjects receive SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 2 weeks
• Drug: Apatinib
  Subjects receive Apatinib orally every day with a dose escalation
• Drug: FOLFOX4
  Subjects receive FOLFOX4 treatment every 2 weeks
• Drug: GEMOX
  Subjects receive GEMOX treatment every 2 weeks

Study Arms

• Experimental: SHR-1210+Apatinib(Arm A）
  Interventions:

  • Biological: SHR-1210
  • Drug: Apatinib
• Experimental: SHR-1210+FOLFOX4 or GEMOX regimen(Arm B）
  Interventions:

  • Biological: SHR-1210
  • Drug: FOLFOX4
  • Drug: GEMOX

Publications *

• Chen X, Qin S, Gu S, Ren Z, Chen Z, Xiong J, Liu Y, Meng Z, Zhang X, Wang L, Zhang X, Zou J. Camrelizumab plus oxaliplatin-based chemotherapy as first-line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial. Int J Cancer. 2021 Dec 1;149(11):1944-1954. doi: 10.1002/ijc.33751. Epub 2021 Sep 8.
• Mei K, Qin S, Chen Z, Liu Y, Wang L, Zou J. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer. 2021 Mar;9(3):e002191. doi: 10.1136/jitc-2020-002191.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2022): 157
• Original Estimated Enrollment (submitted: March 22, 2017): 36
• Actual Study Completion Date: March 31, 2021
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. Histologically confirmed advanced PLC or advanced BTC (including bile duct carcinoma and gallbladder carcinoma) ; not suitable to surgery or local regional treatment; with at least one measurable lesion per RECIST 1.1.
2. Arm A:Failed or intolerable to at least one prior systemic treatment for advanced PLC. Arm B:No previous systemic treatment for advanced PLC or BTC
3. ECOG Performance Status of 0 or1.
4. Child-Pugh Class A or B with 7 points .
5. Life Expectancy of at least 12 weeks.
6. Has controlled infection by Hepatitis B Virus (HBV DNA<500 IU/ml) or Hepatitis C Virus.
7. Adequate organ function.
8. Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug.
9. Patient has given written informed consent.

Exclusion Criteria:

1. Known fibrolamellar HCC; Prior malignancy active with the previous 5 years except for locally curable cancers that have been apparently cured.
2. Known or occurrence of central nervous system (CNS) metastases.
3. Ascites with clinical symptoms.
4. Known or evidence of GI hemorrhage within the past 6 months.
5. Known or occurrence of hemorrhage/ thrombus.
6. Known or evidence of abdomen fistula, gastrointestinal perforation, or abdominal abscess within the past 2 months.
7. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias.
8. Grade III~IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%.
9. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 140mmHg, diastolic blood pressure > 90 mmHg).
10. Factors to affect oral administration (such as patients unable to swallow oral medications, chronic diarrhea and ileus etc. situations evidently affect drug oral medication and absorption).
11. History of hepatic encephalopathy.
12. Known history of human immunodeficiency virus (HIV) infection.
13. Active infection or an unexplained fever > 38.5°C during screening visits.
14. Has received a live vaccine within 30 days.
15. Prior or planning to organ transplantation including liver transplantation.
16. Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity.
17. Proteinuria≥ 2+ or 24 hours total urine protein > 1.0 g.
18. Active known, or suspected autoimmune disease.
19. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily. prednisone equivalent, are permitted in the absence of active autoimmune disease
20. Any loco-regional therapy to liver (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks prior to study.
21. Prior therapy with anti-PD-1 or other anti-PD-1/anti-PD-L1 immunotherapy.
22. Known history of hypersensitivity to monoclonal antibodies or any components of the study drugs.
23. Treatment with anti-coagulation therapy(Warfarin or heparin) or anti-platelet therapy(aspirin at dose≥300mg/day, clopidogrel at dose≥75mg/day).
24. Pregnant or breast-feeding women.
25. According to the investigator, other conditions that may lead to stop the research.

Sex/Gender

• Sexes Eligible for Study: All

• 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: NCT03092895
• Other Study ID Numbers: SHR-1210-APTN-II-203-PLC
• Has Data Monitoring Committee: No

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: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: April 2022