E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Hepatocellular Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Hepatocellular Cancer |
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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 | 27.0 |
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) |
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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 |
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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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female participants must be ≥ 18 years at the time of informed consent. - Participants with histologic confirmed advanced/metastatic 2L or 3L HCC. - Participants with pre-treatment tumor tissue sample with evaluable LAG-3 expression level by IHC. Participants with indeterminate or unevaluable LAG-3 status results will not be permitted to receive study treatment or randomize to a treatment arm. - Participants who have experienced progression that was demonstrated radiographically on or after one or two prior TKI therapies without prior exposure to IO agents. - Child-Pugh score of 5 or 6 points (ie, Child-Pugh A). - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 |
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E.4 | Principal exclusion criteria |
- Women who are pregnant or breastfeeding - Untreated symptomatic central nervous system metastases or leptomeningeal metastases. - Participants with uncontrolled or significant cardiovascular disease. - Prior organ allograft or allogeneic bone marrow transplantation. - Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. - Participants with symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. |
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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) |
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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 |
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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 | 4 |
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 | 4 |
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 |
Argentina |
Chile |
New Zealand |
Singapore |
Hong Kong |
Taiwan |
Brazil |
China |
Japan |
Korea, Republic of |
Russian Federation |
Belgium |
Czechia |
France |
Poland |
Romania |
Spain |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |