Efficacy Study of Nivolumab Compared to Placebo in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIB/C Melanoma (CheckMate 76K)

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

28 Oct 2019 → ongoing

Decision date (initial)

2023-06-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502354-14-00

EudraCT number

2019-001230-34

WHO UTN

U1111-1229-8927

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Pharmacodynamic, Pharmacokinetic, Others, Efficacy, Pharmacogenetic

To compare the efficacy, as measured by recurrence free survival (RFS), provided by nivolumab monotherapy versus placebo in participants with completely resected stage IIB/C melanoma with no evidence of disease

Secondary objectives 4

1. To compare the overall survival (OS) provided by nivolumab monotherapy versus placebo in participants with completely resected stage IIB/C melanoma with no evidence of disease, who are at high risk for recurrence.
2. To assess safety and toxicity of nivolumab monotherapy in participants with completely resected stage IIB/C melanoma with no evidence of disease.
3. To evaluate distant metastases-free survival (DMFS)
4. To evaluate investigator-assessed outcomes on nextline therapies.

Conditions and MedDRA coding

Completely resected Stage IIb/c melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must have been diagnosed with stage IIB/C cutaneous melanoma (AJCC Staging, 8th edition) and have histologically confirmed melanoma that is completely surgically resected with documented negative margins (per local standard) for disease on resected specimens. All melanomas, except ocular and mucosal melanoma, regardless of primary site of disease will be allowed.
2. Complete resection must be performed within 12 weeks prior to randomization. Note: In case of delays exceeding 12 weeks due to unforeseen circumstances, the eligibility should be discussed with the Medical Monitor or designee. Participants must have had a negative sentinel lymph node biopsy. Participants in whom a sentinel lymph node biopsy procedure could not be done or a sentinel lymph node was not detected are not eligible.
3. Participants must have disease-free status documented by a complete physical examination (within 14 days) and imaging studies within 4 weeks (28 days) prior to randomization. Imaging studies must include CT scans of the chest/abdomen/pelvis or CT scan of the chest and MRI scans of the abdomen and pelvis, and all known sites of resected disease (lymph nodes ≥ 15 mm in short axis). Participants with signs and symptoms consistent with brain metastases should have imaging studies done to rule out the presence of brain metastases.
4. Has not been previously treated for melanoma beyond complete surgical resection of the melanoma lesion.
5. Has recovered adequately from toxicity and/or complications from surgery prior to study start.
6. ECOG performance status of 0 or 1 at the time of enrollment
7. Tumor tissue (minimum of 15 unstained slides or 1 FFPE block) from the resected site of disease must be provided to the central laboratory prior to randomization. If the required tumor tissue content cannot be provided, the eligibility should be discussed with the Medical Monitor or designee.

Exclusion criteria 6

1. History of ocular and mucosal melanoma.
2. Participants with 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.
3. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
4. Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
5. Women who are pregnant or breastfeeding
6. Participants with serious or uncontrolled medical disorders.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RFS

Secondary endpoints 7

1. OS
2. AE, clinical laboratory values, vital signs, ECGs, or other safety biomarkers
3. DMFS
4. Objective response rates (if applicable)
5. Duration of treatment on next-line therapies
6. Progression-free survival through next-line therapy (PFS2) is defined as the time from randomization to second recurrence/objective disease progression after the start of the next-line of systemic anti-cancer therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first
7. End-of-next-line-treatment: To be used for situations where PFS2 cannot be reliably determined. Event defined as end or discontinuation of next-line treatment, second objective disease progression, or death from any cause, whichever occurs first.

Investigational products

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

Test 2

Placebo 2

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 14

Locations

15 EU/EEA countries · 73 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

Documents 194 files

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

Application history

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