DISCERN: Deep sequencIng in Cutaneous Squamous CEll caRciNomas

Sponsor

Peter MacCallum Cancer Centre, Australia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05878288

Collaborator

University of Melbourne (Other), University of Adelaide (Other), Monash University (Other), Regeneron Pharmaceuticals (Industry), Sanofi (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To comprehensively describe the molecular profile of the tumour ecosystem of cutaneous squamous cell carcinoma (CSCC) patients treated with neoadjuvant immunotherapy using single-cell sequencing and bulk genomic profiling.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous Squamous Cell Carcinoma Cutaneous Squamous Cell Carcinoma of the Head and Neck Neoplasms Non-melanoma Skin Cancer	Drug: Cemiplimab	Phase 2

Detailed Description

The purpose of this study is to comprehensively assess the molecular profile of the tumour ecosystem of CSCC patients who receive immunotherapy in the neoadjuvant curative setting, in order to identify molecular mechanisms facilitating treatment response and resistance and to identify molecular markers for disease monitoring. Patients who receive immunotherapy for the neoadjuvant management of CSCC will be invited to participate in this translational research study during their treatment journey to provide tumour tissue (fresh and formal-fixed paraffin-embedded, FFPE) and blood samples before and after exposure to immunotherapy.

This study has primarily a translational research objective with the clinical component conducted as a prospective, single-centre, single-arm, open label study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Comprehensive and Deep Profiling in Cutaneous Squamous Cell Carcinomas to Unravel Treatment Efficacy in Immunotherapy Treated Patients

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2029

Anticipated Study Completion Date :

May 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Other: Cemiplimab Cemiplimab 350 mg intravenously every 3 weeks for up to 12 weeks (up to 4 doses), or until unacceptable toxicity, disease progression, or withdrawal of consent.	Drug: Cemiplimab Cemiplimab 50 mg/mL supplied as a sterile liquid in single-use glass vials. Other Names: Libtayo, REGN-2810, REGN2810, cemiplimab-rwlc

Arm

Intervention/Treatment

Other: Cemiplimab

Cemiplimab 350 mg intravenously every 3 weeks for up to 12 weeks (up to 4 doses), or until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: Cemiplimab

Cemiplimab 50 mg/mL supplied as a sterile liquid in single-use glass vials.

Other Names:

Libtayo, REGN-2810, REGN2810, cemiplimab-rwlc

Outcome Measures

Primary Outcome Measures

Rate of successful execution and generation of data from single-cell RNA sequencing and genomic profiling (including whole exome sequencing, RNA sequencing and immunohistochemistry) of CSCC from patients treated with immunotherapy [At 72 months]
Generation of analyzable data from single-cell RNA sequencing and genomic profiling

Secondary Outcome Measures

To evaluate pathological response rates (cPR, mPR defined as <10% viable tumour, and other). [Estimated 48 months]
To evaluate ORR using computed tomography (CT) scan imaging assessed by RECIST 1.1 [Estimated 48 months]
To evaluate ORR using computed tomography (CT) scan imaging assessed by imRECIST [Estimated 48 months]
To summarise immune-related adverse events (AE) > grade 2, AESI, AEs > grade 3 and SAEs, according to CTCAE v5.0. [At 72 months]
To evaluate DFS rates. [Estimated 48 months]
To evaluate OS rates. [Estimated 48 months]

Other Outcome Measures

To describe any changes in the extent of surgical plans with the use of neoadjuvant immunotherapy, comparing plans at baseline and following neoadjuvant therapy. [Estimated 48months]
This outcome will be descriptive.
Describe molecular mechanisms underlying resistance to immunotherapy in CSCC by comparing tumour and TME profiles from immunotherapy responders vs nonresponders defined using pathological response and CT imaging, to identify putative therapeutic targets. [72 months]
The outcome will be descriptive.
Describe whether genomic changes identified in CSCC and TME are detectable in cfDNA and whole blood, and whether these correlate with treatment response. [72 months]
Describe molecular mechanisms underlying response to immunotherapy in CSCC by comparing tumour and TME profiles from immunotherapy responders vs nonresponders defined using pathological response and CT imaging, to identify putative predictive biomarkers. [72 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Stage II to IV (M0) CSCC who are candidates for surgery, but who have an increased risk of recurrence and/or risk of disfigurement or loss of function. Patients with stage III or IV (M0) CSCC of the head/neck, extremity, or trunk are eligible, and patients with stage II CSCC (≥3 cm longest diameter in an aesthetically sensitive region).
At least one measurable lesion per RECIST 1.1.
Age ≥18 years.
Histologically confirmed diagnosis of invasive CSCC.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Anticipated life expectancy >12 weeks.
Adequate organ function defined as:

Hepatic function:

Total bilirubin ≤1.5× upper limit of normal (ULN).
Patients with Gilbert's Disease and total bilirubin up to 3× ULN are eligible.
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤3× ULN.
Alkaline phosphatase (ALP) ≤2.5× ULN. ii) Renal function: Serum creatinine ≤2× ULN or estimated creatinine clearance >35 mL/min (according the method of Cockcroft and Gault). iii) Creatinine phosphokinase (CPK) (also known as CK [creatinine kinase]) elevation ≤ grade 2. iv) Bone marrow function:
Haemoglobin ≥9.0 g/dL.
Absolute neutrophil count (ANC) ≥1.5 x 109/L.
Platelet count ≥75 x 109/L.

Exclusion Criteria:

Active solid malignancy or haematological malignancies including chronic lymphocytic leukaemia, (unless indolent or non-life-threatening) within the last 5 years. For clarity, exceptions include other non-melanoma skin cancer that has undergone potentially curative therapy, or in-situ cervical carcinoma or in-situ prostate cancer with non-detectable prostate specific antigen or any other tumour that has been treated, and the patient is deemed to be in complete remission for at least 2 years prior to enrolment.
Metastatic disease.
Steroid use >10mg prednisone per day within 14 days of study drug (except if physiologic replacement).
Active autoimmune disease requiring active systemic therapy within the last 5 years.
Interstitial lung disease or pneumonitis requiring systemic therapy in the last 5 years.
Active infection requiring therapy including human immunodeficiency virus (HIV)-1 or HIV-2 serum antibody, hepatitis B virus (HBV), or hepatitis C virus (HCV), or active tuberculosis.
Breast-feeding or positive serum pregnancy test consistent with pregnancy (excluding false positives defined as a failure of βHCG doubling in 48 hours) or inability to comply with recommended contraception.
Receipt of live vaccine (including attenuated) within 30 days of first study treatment.
Prior transplant recipient (corneal transplant patients are eligible).
Prior PD-L1/PD-1 inhibitor exposure for the same lesion as enrolment.
Squamous cell carcinoma of unknown primary (those with presumed clinical assessment of CSCC are eligible).
Any anticancer treatment other than radiation therapy (such as chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), either investigational or standard of care, within 30 days of the initial administration of cemiplimab or planned to occur during the study period.
History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments.
Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded.
Institutionalised patients by order of judicial or administrative authority.
Not willing to comply with all study related procedures, particularly consent for collection of tumour and blood samples and imaging, at all protocol specified time points.