Hepatocellular CarcinomaPhase 2/3HCCNCT05408221
the Efficacy and Safety of Rulonilimab in Combination With Lenvatinib in Hepatocellular Carcinoma
A Phase 2/3 study testing Rulonilimab+Lenvatinib in people with Hepatocellular Carcinoma, run by Shandong New Time Pharmaceutical Co., LTD at 5 sites in China.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Rulonilimab+Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 576 participants
- Where
- 5 sitesChina
- Study dates
- 11 Nov 2022to 1 Aug 2026
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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 (+)).
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- 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.
- Central nervous system metastasis; If suspected, an MRI scan of the brain and/or spinal cord should be performed to rule it out.
- For those who received live (attenuated) vaccines within 28 days prior to first administration or who planned to receive vaccines during the study period, the seasonal influenza vaccine for injection or COVID-19 vaccine is usually an inactivated virus vaccine and is allowed to be administered during the study period.
- Presence of immunodeficiency or receiving long-term systemic steroid therapy within 7 days prior to randomization (daily dose >10mg Prednisone or other equivalent glucocorticoid), or other immunosuppressive therapy.
- Active autoimmune diseases requiring systemic treatment (i.e., immunomodulatory drug, corticosteroid or immunosuppressant) in the past two years; Except for:
- alternative therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy due to adrenal or pituitary insufficiency); a patient with well-controlled eczema, psoriasis, chronic simple moss or vitiligo with skin manifestations only, meeting the requirements of a rash ≤10% of body surface area and requiring no systemic drug therapy (including but not limited to hormones, immunosuppressants, etc.).
- History of clear interstitial lung disease or non-infectious pneumonia, unless induced by local radiotherapy.
- Active tuberculosis or received antituberculosis therapy within 1 year prior to randomization.
- Any serious acute and chronic infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, not including viral hepatitis.
- A known history of human immunodeficiency virus (HIV) infection; Treponema pallidum antibody positive; HCV antibody positive and HCV-RNA positive or higher than the upper limit of normal value.
- Previously receiving solid organ transplantation.
- Known contraindication or history of hypersensitivity to any investigational drug or any known excipient.
- Women who are pregnant or lactating, Female subjects at childbearing age or male subjects whose partners are of childbearing potential do not agree with contraception during the study period and for 6 months after the last administration.
- Other participants who are unsuitable for inclusion as judged by the investigator.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites, 5 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100029
- Recruiting
Huizhou Central People's Hospital
Guandong
- Recruiting
Jinan Central Hospital
Shandong
- Recruiting
Linyi Cancer Hospital
Shandong
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
Shenzhen
Xu Che, 18611699566, dr.chex@hotmail.com
About this study
Official title: Phase Ⅱ/III Studies to Investigate the Efficacy and Safety of Rulonilimab in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Hepatocellular Carcinoma
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 .
Read the detailed description
There are two studies included in this protocol. One is an open-label Phase Ⅱ study designed to evaluate the tolerability and safety of lenvatinib in combination with Rulonilimab in participants with hepatocellular carcinoma (HCC). The other is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Rulonilimab in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Rulonilimab+Lenvatinib, Rulonilimab placebo +Lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rulonilimab+LenvatinibDrug
Rulonilimab, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily
Rulonilimab placebo +LenvatinibDrug
Rulonilimab placebo, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily
| Study group | Role | What they receive |
|---|---|---|
| Rulonilimab | Experimental | with PD-1 Inhibitors Receives: Drug: Rulonilimab+Lenvatinib |
| Rulonilimab placebo | Placebo comparator | without PD-1 Inhibitors Receives: Drug: Rulonilimab placebo +Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Objective Response Rate (ORR) Based on RECIST 1.1 Assessed by Independent Review Committee(IRC)
Measured: From randomization to PR or CR.Up to approximately 35 months.
Secondary outcomes (2)
PFS
Progression-free survival (PFS) evaluated by the Blinded Independent Central Review
Measured: From randomization to the first documented disease progression or death due to any cause, whichever occurs first.Up to approximately 35 months.
OS
Overall survival (OS)
Measured: From date of randomization until the date of death from any cause.Up to approximately 35 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2022
- Study start11 Nov 2022
- Primary completion1 Aug 2025 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Shandong New Time Pharmaceutical Co., LTDThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 576 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong New Time Pharmaceutical Co., LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cai Jian qiang, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical SciencesZhou Ai ping, professor, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05408221
- Sponsor's protocol ID
- NTP-F520-401
- Acronym
- HCC
- Status last verified
- Mar 2023
- First submitted
- 2 Jun 2022
- Last updated
- 10 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ⅱ/III Studies to Investigate the Efficacy and Safety of Rulonilimab in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05408221
- Acronym / sponsor ID
- HCC / NTP-F520-401
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 576 participants (estimated)
- Lead sponsor
- Shandong New Time Pharmaceutical Co., LTDIndustry (pharma, biotech, devices)
- Study start
- 11 Nov 2022 (actual)
- Primary completion
- 1 Aug 2025 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 7 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 .
Detailed description
There are two studies included in this protocol. One is an open-label Phase Ⅱ study designed to evaluate the tolerability and safety of lenvatinib in combination with Rulonilimab in participants with hepatocellular carcinoma (HCC). The other is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Rulonilimab in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rulonilimab | Experimental | Drug: Rulonilimab+Lenvatinibwith PD-1 Inhibitors |
| Rulonilimab placebo | Placebo comparator | Drug: Rulonilimab placebo +Lenvatinibwithout PD-1 Inhibitors |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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 .
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rulonilimab+LenvatinibRulonilimab, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily | Drug | Rulonilimab |
| Rulonilimab placebo +LenvatinibRulonilimab placebo, intravenous (i.v.) administration every 3 weeks; Lenvatinib oral administration, once daily | Drug | Rulonilimab placebo |
Primary outcome
ORR
Time frame: From randomization to PR or CR.Up to approximately 35 months.
Objective Response Rate (ORR) Based on RECIST 1.1 Assessed by Independent Review Committee(IRC)
2 secondary outcomes
PFS
Time frame: From randomization to the first documented disease progression or death due to any cause, whichever occurs first.Up to approximately 35 months.
OS
Time frame: From date of randomization until the date of death from any cause.Up to approximately 35 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cai Jian qiang principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Zhou Ai ping, professor principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rulonilimab+Lenvatinib in people with Hepatocellular Carcinoma, run by Shandong New Time Pharmaceutical Co., LTD at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhou Ai ping, professor (13691161998 ext. 13691161998, zhouap1825@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: From randomization to PR or CR.Up to approximately 35 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.