Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
534
Countries
2
Sites
6
Unresectable advanced hepatocellular carcinoma
To compare the efficacy of CS1003 in combination with lenvatinib vs.placebo in combination with lenvatinib
Key facts
- Sponsor
- Cstone Pharmaceuticals (Suzhou) Co. Ltd.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 18 Jan 2021 → 28 Nov 2025
- Decision date (initial)
- 2024-10-31
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Cstone Pharmaceuticals (Suzhou) Co., Ltd.
External identifiers
- EU CT number
- 2024-517331-48-00
- EudraCT number
- 2019-003337-41
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Safety, Pharmacodynamic, Therapy, Dose response, Efficacy, Others
To compare the efficacy of CS1003 in combination with lenvatinib vs.placebo in combination with lenvatinib
Secondary objectives 1
- To compare the efficacy of CS1003 in combination with lenvatinib vs. placebo in combination with lenvatinib. To compare the safety of CS1003 in combination with lenvatinib vs. placebo in combination with lenvatinib. To characterize the population pharmacokinetics (PopPK) and immunogenicity of CS1003 when dosed in combination with lenvatinib. To evaluate the disease/treatment-related patient-reported outcome (PRO), Health related Quality of Life (HRQoL)/Global health status (GHS) and function of subjects treated with CS1003 in combination with lenvatinib compared to placebo in combination with lenvatinib
Conditions and MedDRA coding
Unresectable advanced hepatocellular carcinoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10019828 | Hepatocellular carcinoma non-resectable | 10029104 |
Regulatory references
- EMA paediatric investigation plan (PIP)
- EMEA-002939-PIP01-20
- Plan to share IPD
- No
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 1.Age ≥18 years on the day of signing informed consent (For Taiwan, the lower limit of age is 20 years). 2.Subjects with unresectable advanced HCC that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer [BCLC] staging system) and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the study of Liver Diseases (AASLD) criteria. 3. With at least one measurable lesion can be assessed. 4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. 5. Life expectancy ≥ 3 months. 6. Child-Pugh A. 7. No prior systemic treatment for advanced HCC. 8. Subjects with hepatitis B virus (HBV) infection are willing to continue receiving antiviral treatment while on study. 9. Subjects have adequate organ and marrow function. 10. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use a contraceptive method(s) detailed in the protocol from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose.
Exclusion criteria 1
- 1.Fibrolamellar HCC, sarcomatoid HCC, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC. 2. A prior bleeding event due to esophageal or gastric varices within 6 months or other gastrointestinal bleeding events within 28 days prior to screening. Untreated or incompletely treated esophageal or gastric varices that are considered by the investigator to be at high-risk for bleeding (Note: Patients must undergo an esophagogastroduodenoscopy [EGD], and all size of varices [small to large] must be assessed and treated per local standard of care prior to enrollment; patients who have undergone an EGD within 6 months prior to the initiation of study treatment do not need to repeat the procedure). Active gastric or duodenal ulcer. 3. Malabsorption syndrome or inability to take oral medication due to other causes. 4. HBV and HCV co-infection. 5. Surgery or locoregional therapy for palliative purpose (e.g., to treat bone metastases or metastases causing nerve impingement) within 4 weeks prior to study treatment. 6. History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease. 7. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). 8. Current or prior use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study treatment. 9. History of bone marrow transplantation or organ transplantation. 10. History of anaphylaxis or hypersensitivity to any ingredient of the investigational product. 11. Any contraindication of lenvatinib. 12.Known history of drug abuse that would interfere with cooperation with the requirements of the trial. 13. Pregnant or lactating female subjects. 14. History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability. 15. QTc interval > 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG); 16. Any condition that would in the investigator's judgment, prevent the subject from participating in this study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Overall survival
Secondary endpoints 1
- Objective response rate
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD11454430 · Product
- Active substance
- Nofazinlimab
- Substance synonyms
- Anti-(programmed death-1) IgG4 humanised monoclonal antibody CS1003, Anti-PD-1 IgG4 humanised monoclonal antibody CS1003, CS1003
- Pharmaceutical form
- SOLUTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- CSTONE PHARMACEUTICALS SUZHOU CO. LTD.
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 1
SUB64419 · Substance
- Active substance
- Lenvatinib
- Pharmaceutical form
- HARD CAPSULES
- Route of administration
- ORAL
- Max daily dose
- 12 mg milligram(s)
- Max total dose
- 12 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Cstone Pharmaceuticals (Suzhou) Co. Ltd.
- Sponsor organisation
- Cstone Pharmaceuticals (Suzhou) Co. Ltd.
- Address
- North Block E 168 F 2, 218 Xinghu Road, Wuzhong 218 Xinghu Road Wuzhong
- City
- Suzhou
- Postcode
- 215105
- Country
- China
Scientific contact point
- Organisation
- Cstone Pharmaceuticals (Suzhou) Co. Ltd.
- Contact name
- Seema Harrar
Public contact point
- Organisation
- Cstone Pharmaceuticals (Suzhou) Co. Ltd.
- Contact name
- Seema Harrar
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Veristat International Ireland Limited ORL-000011564
|
Dublin 2, Ireland | On site monitoring, Code 11, Code 12, Code 2 |
Locations
2 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ended | 26 | 3 |
| Spain | Ended | 48 | 3 |
| Rest of world
United States, Taiwan, China
|
— | 460 | — |
Investigational sites
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Onkologii i Radioterapii, Ul. Wawelska 15, 02-034, Warsaw
Centrum Badan Klinicznych Piotr Napora Lekarze sp.p.
Centrum Badań Klinicznych, Ul. Ul. Jana Dlugosza 4, 51-162, Wroclaw
Med Polonia Sp. z o.o.
Department of Cardio-thoracic Surgery, Obornicka 262, 60-693, Poznan
University Clinical Hospital Virgen De La Arrixaca
Hospital Universitario Virgen de la Arrixaca. Servicio de Oncología, Carretera Madrid-Cartagena S/N, El Palmar, Murcia
Hospital Universitario La Paz
Servicio de Hematología, Paseo De La Castellana 261, 28046, Madrid
Hospital Universitario Central De Asturias
Servicio de Aparato Digestivo. Sección de Hepatología, Avenida De Roma S/n, 33011, Oviedo
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Poland | 2021-04-06 | 2025-11-28 | 2021-05-26 | ||
| Spain | 2021-01-18 | 2025-11-28 | 2021-06-04 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-517331-48-00_Redacted | 5.0 |
| Recruitment arrangements (for publication) | Recruitment arrangements_ES_NOTE TO FILE | N/A |
| Recruitment arrangements (for publication) | Recruitment arrangements_PL_NOTE TO FILE | N/A |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_ES | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_PL | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner_ES | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner_PL | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF progression_ES | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF progression_PL | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EN_2024-517331-48-00_Redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ES_2024-517331-48-00_Redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_PL_2024-517331-48-00_Redacted | 5.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Spain | Acceptable 2024-10-29
|
2024-10-29 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-03-24 | Spain | Acceptable 2024-10-29
|
2025-03-24 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-05-29 | Spain | Acceptable 2024-10-29
|
2025-05-29 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2025-08-18 | Spain | Acceptable 2024-10-29
|
2025-08-18 |