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Trial Title:
Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma
NCT ID:
NCT06288191
Condition:
Cutaneous Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Nivolumab
Relatlimab
Conditions: Keywords:
neoadjuvant
immunotherapy
pathological response
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Open label, single arm, single centre, clinical trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Description:
Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways
Arm group label:
Neoadjuvant Treatment
Other name:
Opdualag
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.
Detailed description:
This is a phase 2, open label, single cohort, single centre, clinical trial of
neoadjuvant immunotherapy with dual inhibition of PD-1 and LAG-3 immune checkpoint
pathways. The hypothesis is that neoadjuvant therapy produces a higher pathological
response rate (pCR) and a longer recurrence-free survival in a cohort of treatment-naïve
patients with resectable stage II to IV (M0) cutaneous squamous cell carcinoma compared
to neoadjuvant cemiplimab monotherapy in Checkmate 358 (n=123, NCT02488759, historical
control).
Criteria for eligibility:
Criteria:
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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
July 2024
Completion date:
July 2036
Lead sponsor:
Agency:
Melanoma Institute Australia
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
Melanoma Institute Australia
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06288191