the Efficacy and Safety of Rulonilimab in Combination With Lenvatinib in Hepatocellular Carcinoma

NCT05408221 | Recruiting Phase 2

• 1 other identifier: NTP-F520-401
• Study Type: interventional
• Target: 576
• Locations: 1 country
• Sites: 5

Brief Summary

There are two studies included in this protocol. One is an open-label Phase Ⅱ study . The other is a multi-center, double-blind, randomized, phase III study .

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate (ORR) Based on RECIST 1.1 Assessed by Independent Review Committee(IRC)

  From randomization to PR or CR.Up to approximately 35 months.

Secondary Outcomes (2)

• PFS

  From randomization to the first documented disease progression or death due to any cause, whichever occurs first.Up to approximately 35 months.

• OS

  From date of randomization until the date of death from any cause.Up to approximately 35 months.

Study Arms (2)

Rulonilimab

EXPERIMENTAL

with PD-1 Inhibitors

Drug: Rulonilimab+Lenvatinib

Rulonilimab placebo

PLACEBO COMPARATOR

without PD-1 Inhibitors

Drug: Rulonilimab placebo +Lenvatinib

Interventions

Rulonilimab+Lenvatinib DRUG

Rulonilimab, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily

Rulonilimab

Rulonilimab placebo +Lenvatinib DRUG

Rulonilimab placebo, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily

Rulonilimab placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-75 full years (inclusive), male or female.
• Subjects are with unresectable advanced HCC by histologically or cytologically confirmed diagnosis, Stage B or C based on Barcelona Clinic Liver Cancer \[BCLC\] ,that is not eligible for surgery and/or locoregional therapy or disease progression after surgery and/or locoregional therapy , surgery and/or locoregional therapy must be finished more than 4 weeks before baseline imaging scan .
• Subjects have not received any systemic therapy for HCC previously (mainly including systemic chemotherapy, anti-angiogenic drugs or other molecular targeted therapy, antibodies/drugs targeting T cell co-regulatory proteins (such as anti-CTLA-4, anti-PD-1 /PD-L1, anti-OX-40, anti-CD137, anti-TIM-3, anti-LAG-3 antibodies, etc.).
• Subjects with at least one measurable lesion by RECIST1.1, baseline imaging scan should be performed within 21 days prior to first administration，target lesions located in the field of previous radiotherapy or in the area of local treatment (interventional or ablative) are considered measurable if radiographic progression is confirmed.
• Child-Pugh score A or B (≤7 ），There was no history of hepatic encephalopathy .
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Life expectancy ≥ 12 weeks.
• The functions of vital organs meet the following requirements: No blood transfusion, no hematopoietic stimulating factors (including G-CSF, GM-CSF, EPO, TPO, etc.) and human albumin preparation are required within 14 days before the first administration:
• Blood test: neutrophil count (ANC) ≥1.5×109/L, hemoglobin (HGB) ≥90g/L, platelet count (PLT) ≥75×109/L; liver function: Total bilirubin level (TBIL) ≤2×ULN, ALT and AST≤5×ULN; kidney function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥50mL/min (Cr\>1.5 x ULN); coagulation function: International standardized ratio (INR) ≤1.5×ULN; serum albumin ≥29g/L; urine protein \<2+ (if urine protein ≥2+, 24h urine protein quantification should be performed, 24h urine protein quantification\< 1.0g can be included).
• Subjects with hepatitis B virus infection,and HBV DNA \<2000 IU/mL during the screening period , willing to receive anti-HBV therapy throughout the study period.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

You may not qualify if:

• Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC.
• History of other malignancy(ies) in the past 5 years, except for locally curable cancers (radical melanoma, basal or squamous cell carcinoma, carcinoma in situ of the bladder or cervix, etc.).
• Palliative radiotherapy was performed for bone metastases within 2 weeks prior to firstl administration; Received drugs with anti-liver cancer effect (including Traditional Chinese medicine preparations) within 2 weeks before the first administration.Toxicity induced by previous therapy (except alopecia) not recovered to ≤ grade 1 (NCI-CTCAE v5.0).
• Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate peritoneal effusion at screening.
• Serious, uncured wound, active ulcer or untreated bone fracture.
• History of gastrointestinal hemorrhage within 6 months prior to initial administration or clear tendency of gastrointestinal hemorrhage (including severe esophageal-gastric varices with hemorrhagic risk, locally active peptic ulcer, persistent fecal occult blood (+)).
• Inability to swallow tablets, malabsorption syndrome or any other condition that affects gastrointestinal absorption.
• Having ≥ grade 3 (NCI-CTCAE v5.0) gastrointestinal or non-gastrointestinal fistula at present.
• According to CT/MRI examination, the main portal vein carcinoma thrombus involved the contralateral portal vein branch or the superior mesenteric vein at the same time;inferior vena cava carcinoma thrombus ;
• Serious cardiovascular and cerebrovascular diseases:
• Appears New York Heart Association (NYHA) grade II or above congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident or poorly controlled arrhythmia within 12 months before the first administration (QTc interval ≥480ms, QTc interval calculated by Fridericia formula).
• LVEF (left ventricular ejection fraction) \< 50%; uncontrolled hypertension (systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥100mmHg) (the average of ≥3 BP readings based on ≥2 measurements); has a hypertensive crisis or hypertensive encephalopathy.
• Other obvious hemorrhagic tendency or evidence on important coagulation disorder:
• clinically significant hemoptysis or tumour hemorrhage of any cause within 4 weeks before first administration; a thrombosis or embolism event occurs within 6 months before first administration (e.g., aortic aneurysm or peripheral artery thrombosis requiring surgical repair; Uncontrolled deep vein thrombosis); use of anticoagulant therapy for therapeutic purposes (except low molecular weight heparin) within 2 weeks before first administration; requires antiplatelet therapy.
• Medium or major surgery within 4 weeks prior to initial administration, but diagnostic biopsy was not included.

Sponsors & Collaborators

• Shandong New Time Pharmaceutical Co., LTD: lead

Study Sites (5)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100029, China

RECRUITING

Huizhou Central People's Hospital

Guandong, China

RECRUITING

Jinan Central Hospital

Shandong, China

RECRUITING

Linyi Cancer Hospital

Shandong, China

RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center

Shenzhen, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Cai Jian qiang

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Zhou Ai ping, professor

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhou Ai ping, professor

CONTACT

13691161998; zhouap1825@126.com

Cai Jian qiang, professor

CONTACT

010-67781331; caijianqiang188@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2022
• First Posted: June 7, 2022
• Study Start: November 11, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)