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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06151236




Registration number
NCT06151236
Ethics application status
Date submitted
21/11/2023
Date registered
30/11/2023
Date last updated
15/03/2024

Titles & IDs
Public title
Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma
Scientific title
A Phase 2, Open Label, Single Arm Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage I To III Resectable Merkel Cell Carcinoma
Secondary ID [1] 0 0
CA224-1064
Secondary ID [2] 0 0
MIA2023/489
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Merkel Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination

Experimental: Neoadjuvant Treatment - Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The FDC product contains nivolumab and relatlimab in a protein-mass ratio of 3:1 (nivolumab 240 mg and relatlimab 80 mg): in a 20 mL concentrate solution per single vial. The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. This was primarily based on the observed benefit/risk profile observed in metastatic melanoma patients from Study CA224-020 pharmacokinetics (PK), pharmacodynamics, and extensive nivolumab monotherapy clinical experience. In addition, the Phase 2/3 Study CA224-047 established this dose as active in unresectable and metastatic melanoma.
This study is open label and single arm, with all patients scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29.


Treatment: Drugs: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathological complete response rate
Timepoint [1] 0 0
Week 6
Secondary outcome [1] 0 0
Pathological non-complete response rate to neoadjuvant immunotherapy
Timepoint [1] 0 0
Week 6
Secondary outcome [2] 0 0
Toxicity and tolerability of neoadjuvant immunotherapy and surgery
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Objective response rate to neoadjuvant immunotherapy
Timepoint [3] 0 0
Week 6
Secondary outcome [4] 0 0
Metabolic response rate to neoadjuvant immunotherapy
Timepoint [4] 0 0
Week 6
Secondary outcome [5] 0 0
Recurrence-free survival
Timepoint [5] 0 0
10 years
Secondary outcome [6] 0 0
Disease progression rate
Timepoint [6] 0 0
Week 6
Secondary outcome [7] 0 0
Event-free survival rate
Timepoint [7] 0 0
10 years
Secondary outcome [8] 0 0
Overall survival rate
Timepoint [8] 0 0
10 years
Secondary outcome [9] 0 0
Patient reported quality of life
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
Study treatment completion rate
Timepoint [10] 0 0
Week 8

Eligibility
Key inclusion criteria
- Aged = 18 years

- Written consent Histologically confirmed, resectable Merkel cell carcinoma with AJCC
(8th ed) clinical stage I (= 10 mm), II, or III

- In-transit metastases are permitted if they are completely resectable

- Measurable disease according to RECIST 1.1 criteria

- Tumour amenable to core biopsy

- Previous radiotherapy permitted if there is RECIST-measurable progression of disease
since the completion of radiotherapy

- ECOG 0-1

- Adequate organ function on blood pathology

- Life expectancy >12 months

- Female patients to use effective contraception during study treatment and for 5 months
after last dose.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinical or radiographic evidence of distant metastases

- Contraindication to nivolumab and / or relatlimab

- Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to
another stimulatory or co-inhibitory T-cell receptor for any disease or any
chemotherapy or experimental local or systemic drug treatment

- Active autoimmune disease or requirement for chronic steroid therapy other than
hormone replacement therapy

- A diagnosis of immunodeficiency or chronic steroid therapy >10 mg OD prednisone or
equivalent

- Additional malignancy active within past 3 years; patients with chronic lymphocytic
leukaemia can be included in this study.

- Uncontrolled cardiovascular disease or history of myocarditis - Has had an allogenic
tissue/solid organ transplant

- Active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or
Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.

- Known HIV

- Pregnant or breast feeding females

- Concurrent medical or social conditions that may prevent the patient attending
assessments or procedures per schedule

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2034
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this clinical trial is to test neoadjuvant dual immunotherapy in Merkel cell
carcinoma with the aim to improve recurrence-free survival
Trial website
https://clinicaltrials.gov/ct2/show/NCT06151236
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ines Esteves Domingues Pires da Silva
Address 0 0
Melanoma Instiute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Monica Osorio
Address 0 0
Country 0 0
Phone 0 0
+ 61 2 9911 7296
Fax 0 0
Email 0 0
monica.osorio@melanoma.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06151236