E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Participants With Advanced Melanoma Who Progressed on Anti-PD-1 Treatment |
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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 | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
-For dose escalation (part 1): To characterize the safety, and dose-limiting toxicities (DLTs) and to determine the Bayesian Logistic
Regression Model (BLRM) recommended dose of relatlimab in combination with ipilimumab
- For randomized dose expansion (part 2) : To evaluate the
safety and tolerability of the BLRM recommended dose of relatlimab in combination with ipilimumab and ipilimumab monotherapy
- For randomized dose expansion cohort (part 2): To compare Blinded Independent Central Review (BICR)-assessed objective response rate (ORR) obtained with relatlimab plus ipilimumab to ipilimumab monotherapy |
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E.2.2 | Secondary objectives of the trial |
For randomized dose expansion cohort (part 2):
-To evaluate BICR-assessed duration of response (DOR) obtained with relatlimab plus ipilimumab and ipilimumab monotherapy
-To evaluate BICR-assessed DOR with continued relatlimab monotherapy treatment
-To compare Investigator-assessed ORR obtained with relatlimab plus ipilimumab to ipilimumab monotherapy
- To evaluate Investigator-assessed DOR with relatlimab plus ipilimumab and ipilimumab monotherapy
- To compare investigator-assessed and BICR assessed progression-free survival (PFS) with relatlimab plus ipilimumab to ipilimumab
monotherapy
- To compare overall survival (OS) with relatlimab plus ipilimumab to ipilimumab monotherapy
- To characterize the immunogenicity of relatlimab and ipilimumab when administered in combination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Must have documented progression while on a prior anti-programmed cell death protein 1 (PD-1) containing regimen limited to Nivolumab or Pembrolizumab.
•Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test
•Participants must have histologically confirmed advanced unresectable (Stage III) or metastatic (Stage IV) melanoma, as per AJCC staging system
•Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses.
•BRAF wild type and mutant participants are eligible
•Eastern Cooperative Oncology Group (ECOG) 0-1
•Ability to comply with treatment, patient-reported outcomes (PROs), PK, and pharmacodynamic sample collection and required study follow-up
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E.4 | Principal exclusion criteria |
•History of uveal melanoma
•Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
•Prior treatment with ipilimumab, relatlimab, or any other CTLA-4 or LAG-3 targeted agents
•Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 and HIV-2 antibody.
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Number of Participants with Adverse Events (AEs)
2.Number of Participants with Serious Adverse Events (SAEs)
3.Number of Participants With Adverse Events Including Dose Limiting Toxicity
4.Number of Participants with AEs resulting in Discontinuation
5.Number of Participants with AEs resulting in Death
6.Number of Participants with AEs resulting in Laboratory Abnormalities
7.Objective Response Rate (ORR) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 and 2: Up to Follow-up Period (100 days after 34 cycles [1 cycle is of 3 weeks])
3.Up to 28 days after last study drug dose (approximately up to 2 years)
4 to 7: Up to end of study (approximately 2.4 years)
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|
E.5.2 | Secondary end point(s) |
1.Duration of response (DOR)
2.Median Progression-Free Survival (PFS)
3.Median Overall Survival (OS)
4.Number of Participants with Anti-Drug Antibodies (ADA)-Positivity
5.Progression Free Survival rates (PFS rates)
6.Overall Survival Rates (OS rates)
7.Objective Response Rate (ORR) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Approximately Up to 2.4 years
2. 6 and 12 months
3. 1 and 2 years
4. Up to Follow-up Period (100 days after 34 cycles [1 cycle is of 3 weeks])
5. at 24 weeks and at 1 year
6. at 1 year and at 2 years
7. Up to 2.4 years |
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
safety and tolerability of relatlimab and ipilimumab |
|
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 | 2 |
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 | 14 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Spain |
Sweden |
United States |
|
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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 8 |