Adjuvant Immunotherapy with Nivolumab + Relatlimab Fixed-dose Combination versus Nivolumab Monotherapy after Complete Resection of Stage III-IV Melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol Myers Squibb International Corporation

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Dec 2021 → 2 Apr 2025

Decision date (initial)

2024-03-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507688-20-00

EudraCT number

2021-001641-13

WHO UTN

U1111-1266-6146

ClinicalTrials.gov

NCT05002569

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Safety, Therapy, Pharmacokinetic

To compare the efficacy, as measured by RFS, provided by nivo + rela
FDC vs nivolumab monotherapy in participants with completely resected
Stage III/IV NED melanoma.

Secondary objectives 4

1. Key secondary: To compare the OS provided by nivo + rela FDC vs nivolumab monotherapy in participants with completely resected Stage III/IV NED melanoma.
2. To assess the efficacy, as measured by distant metastasis-free survival (DMFS), provided by nivo + rela FDC vs nivolumab monotherapy in participants with completely resected Stage III/IVA/IVB NED melanoma.
3. To assess safety and toxicity of nivo + rela FDC vs nivolumab monotherapy in participants with completely resected Stage III/IV NED melanoma.
4. To evaluate investigator-assessed outcomes on next-line systemic therapies.

Conditions and MedDRA coding

Participants with completely resected Stage III or Stage IV melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. All participants must have been diagnosed with either Stage IIIA (> 1 mm tumor in lymph node)/B/C/D or Stage IV melanoma by AJCC v8 and have histologically confirmed melanoma that is completely surgically resected (free of disease) with negative margins in order to be eligible. All melanomas, except ocular melanoma, regardless of primary site of disease, will be allowed. Note: Conjunctival melanoma is not considered to be ocular melanoma and is to be classified as mucosal melanoma.
2. All participants must have disease-free status documented by a complete physical examination within 14 days prior to randomization and imaging studies within 35 days prior to randomization.
3. Tumor tissue obtained from surgical specimen or biopsy during resection collected within 90 days prior to randomization, with an associated pathology report, must be submitted to the central laboratory (preferably prior to randomization).
4. Participant must be ≥ 12 years of age inclusive at the time of signing the informed consent. Except: Where local regulations and/or institutional policies do not allow for participants < 18 years of age (adolescent population) to participate. For those sites, the eligible participant population is ≥ 18 years of age.
5. Participants ≥ 18 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Adolescent participants between 12 and <18 years of age must have a Lansky/Karnofsky performance score ≥ 80%.

Exclusion criteria 6

1. Prior immunotherapy treatment for any prior malignancy: No prior immunotherapies are permitted (such as, but not limited to, antiprogrammed death-1 (anti-PD-1), anti-programmed death ligand-1 (anti-PD-L1), anti-programmed death ligand-2 (PD-L2), or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways).
2. Prior treatment with LAG-3 targeted agents
3. Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions.
4. 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.
5. Participants with a history of myocarditis, regardless of etiology.
6. Prior treatment with BRAF/MEK targeted agents.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RFS time as assessed by the investigator. RFS is defined as the time between the date of randomization and the first date of documented recurrence (local, regional, distant, new primary melanoma), or death due to any cause, whichever occurs first. Comparison of relatlimab and nivolumab FDC vs nivolumab monotherapy.

Secondary endpoints 4

1. OS is defined as the time between the date of randomization and the date of death due to any cause. Comparison of relatlimab and nivolumab FDC vs nivolumab monotherapy.
2. DMFS, by investigator, is defined as the time between the date of randomization and the date of first distant metastasis or date of death due to any cause, whichever occurs first. Comparison of relatlimab and nivolumab FDC vs nivolumab monotherapy.
3. Incidence and severity of AE, SAEs, AEs leading to DC, IMAEs, drugrelated AEs, deaths, laboratory abnormalities, and other select AEs, in all treated participants.
4. PFS2 defined as time from randomization to second recurrence/objective disease progression on next-line systemic therapy per investigator, or death from any cause, whichever occurs first. Evaluation of relatlimab and nivolumab FDC vs nivolumab monotherapy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol Myers Squibb International Corporation

Sponsor organisation

Bristol Myers Squibb International Corporation

Address

Terhulpsesteenweg 185

City

Watermaal-Bosvoorde

Postcode

1170

Country

Belgium

Scientific contact point

Organisation

Bristol Myers Squibb International Corporation

Contact name

GSM-CT

Public contact point

Organisation

Bristol Myers Squibb International Corporation

Contact name

GSM-CT

Third parties 10

Locations

13 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications