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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06288191




Registration number
NCT06288191
Ethics application status
Date submitted
4/02/2024
Date registered
1/03/2024
Date last updated
9/01/2025

Titles & IDs
Public title
Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma
Scientific title
A Phase 2, Open Label, Single Arm, Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage II to IV (M0) Resectable Cutaneous Squamous Cell Carcinoma
Secondary ID [1] 0 0
CA224-1065
Secondary ID [2] 0 0
MIA2023/490
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Squamous Cell Carcinoma 0 0
Condition category
Condition code
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 dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. All patients are scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29. Patients without a complete pathological response to neoadjuvant therapy may receive standard of care radiotherapy per multidisciplinary team meeting discussion.


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 near pathological response (near pCR), partial response (pPR) and pathological non-response (pNR) rate
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 therapy
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
Timepoint [8] 0 0
10 years
Secondary outcome [9] 0 0
Patient reported quality of life (QLQ-C30)
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
Patient reported quality of life (EQ-5L-5D)
Timepoint [10] 0 0
1 year
Secondary outcome [11] 0 0
Study treatment completion rate and the causes of any missed treatments
Timepoint [11] 0 0
Week 8
Secondary outcome [12] 0 0
De-escalation of adjuvant radiotherapy.
Timepoint [12] 0 0
Week 8

Eligibility
Key inclusion criteria
1. = 18 years of age
2. Written informed consent
3. Histologically confirmed, resectable stage II to IV cutaneous squamous cell carcinoma defined as:

Non-head and neck cuSCC:
1. stage II (T2, N0, M0)
2. stage III (T3, N0, M0; or T1-3, N1, M0)
3. stage IV (T1-3, N2 or N3, M0; or T4a or T4b, any N, M0)

Cutaneous head and neck CC:
1. stage II (T2, N0, M0)
2. stage III (T3, N0, M0)
3. stage IV (T4a or T4b, any N, M0)
4. In-transit metastases (ITM) are permitted if they are completely resectable. ITM defined as skin or subcutaneous metastases that are > 20 mm from the primary lesion but not beyond the regional nodal basin.
5. Measurable disease according to RECIST version 1.1 criteria (=10 mm longest diameter for primary lesions and / or =15 mm in shortest diameter for lymph nodes as determined by CT imaging) within 2 weeks of the start of study treatment.
6. Tumour amenable to a newly obtained core biopsy of a lesion which has not been previously irradiated. Archival tissue from a past primary or nodal cuSCC lesion (if applicable) or tissue taken for current diagnosis will also be collected.
7. Previous radiotherapy permitted if performed at a prior site of disease not seen at baseline.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
9. Documented adequate haematological, hepatic, renal, and thyroid function determined by blood pathology
10. Anticipated life expectancy of > 12 months
11. Women of childbearing potential must have a negative serum pregnancy test within 24 hours of the first dose of study treatment or within 72 hours if this is not feasible. Effective contraception should be used for the duration of study treatment and for 5 half-lives (or 5 months) after the last dose. Egg donation (ova, oocytes) should be avoided for the same period. There are no partner-pregnancy or sperm donation avoidance requirements for male patients.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinical or radiographic evidence of distant metastasis
2. SCC of the eyelid, vulva, penis and perianus
3. Any contraindication to the administration of nivolumab and / or relatlimab
4. Prior anti-PD-1, CTLA-4 (Cytotoxic T-lymphocyte associated protein 4), PDL-1 (Programmed death-ligand 1) or LAG 3 (Lymphocyte-Activation Gene 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
5. Active autoimmune disease or a requirement for chronic steroid therapy other than hormone replacement therapy

The following are permitted:
* Vitiligo
* Type I diabetes mellitus on stable insulin therapy
* Residual autoimmune hypothyroidism on stable hormone replacement
* Resolved childhood asthma or atopy
* Psoriasis not requiring systemic treatment
* Autoimmune conditions which are not expected to recur in the absence of an external trigger.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment.

The following are permitted:
* Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.)
* Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient is on a stable dose
* Non-absorbed intra-articular steroid injections.
7. Known additional malignancies (unless adequately treated) active within the previous 3 years, except for locally curable cancers that have been apparently cured.

The following malignancies, if undergone successful definitive resection or curative treatment, are permitted:
* Basal cell carcinoma of the skin
* Squamous cell carcinoma of the skin
* Carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, but excluding carcinoma in situ of the bladder) that have undergone potentially curative therapy
* Prostatic intraepithelial neoplasia
* In situ melanoma
* Atypical melanocytic hyperplasia
* Multiple primary melanomas
* Other malignancies for which the patient has been disease free for 3 years, not requiring active anti-cancer therapy.
8. Uncontrolled or significant cardiovascular disease including, but not limited to any of the following:

* Myocardial infarction (MI) or stroke/transient ischemic attack within the 6 months prior to consent
* Uncontrolled angina within the 3 months prior to consent
* Any history of clinically significant arrhythmias (such as poorly controlled atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
* QTc (corrected QT interval) prolongation > 480 ms
* History of other clinically significant cardiovascular disease (i.e. cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled venous thrombosis, etc)
* Cardiovascular disease-related requirement for daily supplemental oxygen
* History of 2 or more M.I.s OR 2 or more coronary revascularisation procedures (regardless of the number of stent placements during each procedure)
* Patients with history of myocarditis, regardless of aetiology.
9. Troponin T (TnT) or I (TnI) >2 × institutional ULN (upper limit of normal). Participants with TnT or TnI levels between >1 to 2 × ULN will be permitted if repeat levels within 24 hours are =1 ULN. If TnT or TnI levels are between >1 to 2 × ULN within 24 hours, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are <2 × ULN, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. Notification of the decision to enrol the participant following cardiologist recommendation must be made to the Lead Investigator.
10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease.
11. Has an active infection requiring systemic therapy.
12. Has had an allogenic tissue/solid organ transplant
13. Has a known history of Human Immunodeficiency Virus (HIV). Note: no testing for HIV is required unless mandated by local health authority.
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
15. Pregnant or breast-feeding females
16. Concurrent medical or social conditions that may prevent the patient from attending assessments per schedule.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
21/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2036
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 study is to test neoadjuvant therapy with the dual inhibition of Programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) immune checkpoint pathways in a cohort of treatment-naïve, resectable stage II to IV cutaneous squamous cell carcinoma on the pathological response rate (pCR) and recurrence-free survival.
Trial website
https://clinicaltrials.gov/study/NCT06288191
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ines 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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06288191