Safety and Efficacy Study of Sintilimab Combined With IBI305 in Patients With Advanced Hepatocellular Carcinoma

• ClinicalTrials.gov Identifier: NCT04072679
• Recruitment Status: Completed
• First Posted: August 28, 2019
• Last Update Posted: February 1, 2021
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Information provided by (Responsible Party): Aiping Zhou, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Tracking Information

• First Submitted Date: August 23, 2019
• First Posted Date: August 28, 2019
• Last Update Posted Date: February 1, 2021
• Actual Study Start Date: October 11, 2018
• Actual Primary Completion Date: March 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2019)

Incicende of Adverse Events (AEs) [ Time Frame: 2 years ]

Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE) assessed by CTCAE v5.0.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2019)

• Objective Response Rate (ORR) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Time to response (TTR) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Duration of response (DOR) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Disease control rate (DCR) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Progression free survival (PFS) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Overall Survival (OS) [ Time Frame: 2 years ]
  Investigator assessed according to RECIST v1.1
• Anti-drug antibody (ADA) [ Time Frame: 2 years ]
  Immunogenicity measured by anti-drug antibody (ADA) for Sintilimab and IBI305

• 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: Safety and Efficacy Study of Sintilimab Combined With IBI305 in Patients With Advanced Hepatocellular Carcinoma
• Official Title: Evaluation of the Safety and Efficacy of Sintilimab Combined With IBI305 in the Treatment of Advanced Hepatocellular Carcinoma in a Single-center, One-arm, and Phase Ib Study
• Brief Summary: This is a Phase Ib study to evaluate the safety, tolerability and efficacy of Sintilimab combined with IBI305 in patients with advanced hepatocellular carcinoma in China.

Detailed Description

This study is to evaluate the safety, tolerability and efficacy of Sintilimab combined with IBI305 in patients with advanced hepatocellular carcinoma in China.

Approximately 26-38 subjects with locally advanced or metastatic hepatocellular carcinoma will be enrolled in the study. It includes dose escalation and dose expansion stage. 12-18 subjects will be enrolled in dose escalation stage for the safety and efficacy evaluation. Then select specific dose of IBI305 +Sintilimab 200mg/kg, expand to 20 patients for the further safety and efficacy study.

The study treatment lasts up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Hepatocellular Carcinoma

Intervention

Drug: Sintilimab+IBI305

It includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety and efficacy evaluation. Then select specific dose of IBI305 +Sintilimab 200mg/kg, expand to 36-39 patients for the further safety and efficacy study.The study treatment lasts up to 24 months.

Study Arms

Experimental: Sintilimab+IBI305

Sintilimab: 200mg (D1, q3w） IBI305: 7.5mg/kg or 15mg/kg (D1, q3w）

Intervention: Drug: Sintilimab+IBI305

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2021): 50
• Original Estimated Enrollment (submitted: August 27, 2019): 45
• Actual Study Completion Date: November 11, 2020
• Actual Primary Completion Date: March 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Local advanced or metastatic hepatocellular carcinoma, confirmed by histology/cytology.
2. Barcelona Clinic Liver Cancer (BCLC) C. BCLC B, unsuitable for local treatments or local treatments failure.
3. Patients who failed to or unsuitable for the previously systemic chemotherapy, sorafenib, lenvatinib, regorafenib or similar drug failure (disease progression or toxicity intolerance).
4. At least one measurable lesion per RECIST V1.1 that has not been treated locally or that has progressed after local treatment.
5. Child-Pugh score ≤ 7 points.
6. ECOG：0 or 1.
7. Adequate organ and bone marrow function.

Exclusion Criteria:

1. With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues.
2. Have a history of hepatic encephalopathy or have a history of liver transplantation.
3. HBV DNA>2000 IU/ml or 104 copies/ml for acute or chronic active hepatitis B or hepatitis C; HCV RNA>103 copies/ml; both HbsAg and anti-HCV antibody are positive.
4. Esophageal or gastric varices bleeding caused by portal hypertension occurred in the past 6 months. Patients with endoscopy evidence of severe varices (G3) within 3 months. Patients with portal hypertension in high risk of bleeding evaluated by investigator.
5. History of venous thromboembolism in the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other history of severe thromboembolism. Implantable IV ports or catheter-derived thrombosis, superficial venous thrombosis, or thrombosis after conventional anticoagulant therapy are excluded. Prophylactic uses of low-dose aspirin or low molecular weight heparin is allowed.
6. Portal vein tumor thrombus (PVTT) involves both the main trunk and contralateral branch or upper mesenteric vein. Inferior vena cava tumor thrombus.
7. Uncontrolled high blood pressure, systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg after optimal medical treatment; Hypertensive crisis or history of hypertensive encephalopathy.
8. History of gastrointestinal perforation and/or fistula in the past 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) , complicated by chronic diarrhea), Crohn's disease, ulcerative colitis or long-term chronic diarrhea.
9. History of interstitial pneumonia, drug-induced pneumonia, idiopathic pneumonia or active pneumonia. Allow radioactive pneumonia in the radiotherapy area.
10. Active tuberculosis (TB), who are receiving anti-tuberculosis treatment or who have received anti-tuberculosis treatment within 1 year before inclusion.
11. HIV infected (HIV 1/2 antibody positive).
12. Use of immunosuppressive drugs in the past 4 weeks, excluding the routes of topical glucocorticoids or physiological doses of systemic glucocorticoids (ie no more than 10 mg/day of prednisone or equivalent). Temporary use of glucocorticoids for dyspnea symptoms such as asthma and chronic obstructive pulmonary disease is allowed.
13. Have undergone major surgery (craniotomy, thoracotomy or open surgery) or unhealed wounds, ulcers or fractures within 4 weeks.
14. Previously received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA4 antibodies, or other immunotherapy; previously received anti-VEGF monoclonal antibody treatment.
15. Female patients who are pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 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: NCT04072679
• Other Study ID Numbers: CIBI338B101
• Has Data Monitoring Committee: Not Provided

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: Not Provided
• Current Responsible Party: Aiping Zhou, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Aiping Zhou Zhou, Doctor; National Cancer Center/Cancer Hospital, China

• PRS Account: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Verification Date: January 2021