Deep sequencIng in Cutaneous Squamous CEll caRciNomas

NCT05878288 | Active Not Recruiting Phase 2

• 1 other identifier: HREC/88736/PMCC-2022-326880
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Cutaneous Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma of the Head and Neck; Neoplasms; Non-melanoma Skin Cancer

Keywords

single-cell sequencing; molecular profiling; neoadjuvant; immunotherapy; cemiplimab

Outcome Measures

Primary Outcomes (1)

• 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

  Generation of analyzable data from single-cell RNA sequencing and genomic profiling

  At 72 months

Secondary Outcomes (6)

• 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

Other Outcomes (4)

• 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

• 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

• 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

Study Arms (1)

Cemiplimab

OTHER

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

Interventions

Cemiplimab DRUG

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

Also known as: Libtayo, REGN-2810, REGN2810, cemiplimab-rwlc

Cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• i) 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:
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• Haemoglobin ≥9.0 g/dL.
• Absolute neutrophil count (ANC) ≥1.5 x 109/L.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• University of Melbourne: collaborator
• University of Adelaide: collaborator
• Monash University: collaborator
• Regeneron Pharmaceuticals: collaborator
• Sanofi: collaborator

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Neoplasms

Interventions

cemiplimab

Study Officials

• Annette M Lim, MBBS, FRACP, PhD

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2023
• First Posted: May 26, 2023
• Study Start: May 26, 2023
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)