E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Hepatocellular Carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Hepatocellular Cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077738 |
E.1.2 | Term | Hepatocellular carcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of relatlimab in combination with nivolumab relative to nivolumab monotherapy in IO therapy-naive participants after prior treatment with TKI therapy |
|
E.2.2 | Secondary objectives of the trial |
- To investigate safety and tolerability of relatlimab in combination with nivolumab in participants with advanced HCC
- To further evaluate the preliminary efficacy of relatlimab in combination with nivolumab
- To characterize the dose-response relationship of relatlimab in combination with nivolumab
- To assess the association of LAG-3 expression by IHC with clinical response |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have a diagnosis of hepatocellular carcinoma (HCC) based on histological confirmation
- Must have advanced/metastatic HCC
- Have to be immunotherapy treatment-naive; no prior immunotherapies are permitted
- Must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measurable untreated lesion
- Child-Pugh score of 5 or 6
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 for ECOG performance status scale |
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E.4 | Principal exclusion criteria |
- Known fibrolamellar HCC, sarcomatoid HCC, combined hepatocellular cholangiocarcinoma
- Prior organ allograft or allogeneic bone marrow transplantation
- No uncontrolled or significant cardiovascular disease
- No active known autoimmune disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) assessed by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years after first dose of treatment |
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E.5.2 | Secondary end point(s) |
1. Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), death and AEs leading to discontinuation
2. Incidence of clinically significant changes in clinical laboratory results: Hematology, Clinical Chemistry and Urinalysis tests
3. Disease control rate (DCR), Duration of response (DOR) and Progression-free survival assessed by BICR per RECIST v1.1
4. ORR, DCR, DOR and PFS assessed by investigator per RECIST v1.1
5. Overall survival (OS)
6. Dose: participant's actual dose as treated
7. Response: participant’s best overall response (BOR) assessed by BICR using RECIST v1.1
8. LAG-3 expression by Immunohistochemistry (IHC): participant’s actual LAG-3 expression value dichotomized into ≥ 1% and < 1%
9. Response: participant’s BOR assessed by BICR using RECIST v1.1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2. Up to approximately 2.5 years
3, 4. Up to 2 years after first dose of treatment
5. Up to 3 years after first dose of treatment
6. Up to 8 weeks
7. Up to 2 years after first dose of treatment
8. Up to 1 month
9. Up to 2 years after first dose of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Chile |
China |
Hong Kong |
Japan |
Korea, Republic of |
New Zealand |
Russian Federation |
Singapore |
Taiwan |
Belgium |
France |
Poland |
Romania |
Spain |
Czechia |
Argentina |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
the end of Survival Follow-up period of the last participant |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 29 |