| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Colorectal Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Metastatic Colorectal 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 | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052358 |
| E.1.2 | Term | Colorectal cancer 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 compare the efficacy of the relatlimab-nivolumab FDC to investigator’s choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1, respectively |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the antitumor activity based on ORR by BICR of the relatlimab-nivolumab FDC to investigator’s choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥1
- To compare the antitumor efficacy based on PFS by BICR of the relatlimab-nivolumab FDC to investigator’s choice standard of care therapy (regorafenib or TAS-102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1
- To compare deterioration free survival (DeFS) of the relatlimab + nivolumab FDC to investigator’s choice standard of care therapy (regorafenib or TAS- 102) in participants with late-line metastatic colorectal cancer, including all randomized participants and randomized participants with PD-L1 CPS ≥ 1 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Histologically confirmed previously treated CRC with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry.
- Participants must have:
a)progressed during or within approximately 3 months following the last administration of approved standard therapies in the metastatic setting (at least 1, but not more than 4 prior lines of therapies), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type), if approved in the respective country, or;
b)been intolerant to prior systemic chemotherapy regimens if there is documented evidence of clinically significant intolerance despite adequate supportive measures.
- Participants must have sufficient tumor tissue & evaluable PD-L1 expression to meet the study requirements. Participants with indeterminate PD-L1 results will be stratified with those participants assessed to be PD-L1 negative by CPS (see next slide for details).
- KRAS mutation status must be documented based on available historical or local testing results as part of medical history prior to study enrollment.
- Participants must have measurable disease per RECIST v1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately.
For all Inclusion Criteria please refer to the Protocol. |
|
| E.4 | Principal exclusion criteria |
- Prior treatment with either an immunotherapy (anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or with regorafenib or with TAS-102.
- Untreated CNS metastases. Participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment)
- Participants with history of refractory hypertension not controlled with anti-hypertensive therapy, myocarditis (regardless of etiology), uncontrolled arrhythmias, acute coronary syndrome within 6 months prior to dosing, Class II congestive heart failure (as per the New York Heart Association Functional Classification), interstitial lung disease/pneumonitis or an active, known or suspected autoimmune disease.
- In the case of prior SARS-CoV-2 infection, acute symptoms must have completely resolved and based on investigator assessment in consultation with the clinical trial physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment.
- Participants with historically or locally confirmed tumor MSI-H/dMMR
status
For all Exclusion Criteria, please refer to the Protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Overall Survival (OS) in randomized participants with PD-L1 CPS (combined positive score;) ≥ 1
- OS in all randomized participants
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Until death, up to 5 years after last Participant randomized
|
|
| E.5.2 | Secondary end point(s) |
1/ ORR (objective response rate) by BICR (blinded independent central review) per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, respectively
2/ PFS (progression-free survival) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS≥ 1 and all randomized participants, respectively
3/ DoR (duration of response;) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1 and all responders, respectively
4/ Rate of AEs (adverse events), SAEs (serious adverse events), select AEs and IMAEs (immune-mediated adverse events), AEs leading to discontinuation and abnormalities in specific clinical laboratory assessments
5/ QoLTUDD-physical function (TUDDPF), which is defined as time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, respectively
6/ TUDD-quality of life (TUDD-QoL), which is defined as time until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in randomized participants with PD-L1 CPS ≥ 1 and all randomized participants, Respectively
7/ PFS, ORR, DoR by investigator per RECIST v1.1 in randomized
participants with PD-L1 CPS = 1 and all randomized participants,
respectively |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2, 3: Tumor assessments should continue until disease progression or death or withdrawal of consent, whichever is earlier, up to 5 years after last participant randomized
4: up to follow up visit 2, which is 135 days after last dose.
5, 6: up to follow up visit 2, which is 135 days after last dose.
7: Tumor assessments should continue until disease progression or
death or withdrawal of consent, whichever is earlier, up to 5 years after
last participant randomized |
|
| 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 | No |
| 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) | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| 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 |
| Australia |
| Canada |
| Chile |
| China |
| Japan |
| Korea, Republic of |
| Singapore |
| Taiwan |
| United States |
| Switzerland |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Spain |
| Sweden |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
End of trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last participant.
A participant is considered to have completed the study if he/she has completed all survival follow-up visits up to 5 years. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 7 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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