Deep sequencIng in Cutaneous Squamous CEll caRciNomas (DISCERN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Cutaneous Squamous Cell Carcinoma of the Head and Neck; Non-melanoma Skin Cancer; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cemiplimab

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
      • Principal Investigator: Annette M Lim, MBBS, FRACP, PhD
      • Contact: Annette Lim; Phone Number: +61 3 8559 5000; Email: annette.lim@petermac.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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).
2. At least one measurable lesion per RECIST 1.1.
3. Age ≥18 years.
4. Histologically confirmed diagnosis of invasive CSCC.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Anticipated life expectancy >12 weeks.

7. Adequate organ function defined as:

   i) Hepatic function:

   1. Total bilirubin ≤1.5× upper limit of normal (ULN).
   2. Patients with Gilbert's Disease and total bilirubin up to 3× ULN are eligible.
   3. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤3× ULN.
   4. 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:
   1. Haemoglobin ≥9.0 g/dL.
   2. Absolute neutrophil count (ANC) ≥1.5 x 109/L.
   3. Platelet count ≥75 x 109/L.

Exclusion Criteria:

1. 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.
2. Metastatic disease.
3. Steroid use >10mg prednisone per day within 14 days of study drug (except if physiologic replacement).
4. Active autoimmune disease requiring active systemic therapy within the last 5 years.
5. Interstitial lung disease or pneumonitis requiring systemic therapy in the last 5 years.
6. 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.
7. 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.
8. Receipt of live vaccine (including attenuated) within 30 days of first study treatment.
9. Prior transplant recipient (corneal transplant patients are eligible).
10. Prior PD-L1/PD-1 inhibitor exposure for the same lesion as enrolment.
11. Squamous cell carcinoma of unknown primary (those with presumed clinical assessment of CSCC are eligible).
12. 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.
13. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments.
14. Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded.
15. Institutionalised patients by order of judicial or administrative authority.
16. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
To describe any changes in the extent of surgical plans with the use of neoadjuvant immunotherapy, comparing plans at baseline and following neoadjuvant therapy.	This outcome will be descriptive.	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.	The outcome will be descriptive.	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
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

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Collaborators: Sanofi; Regeneron Pharmaceuticals; Monash University; University of Adelaide; University of Melbourne
• Investigators: Principal Investigator: Annette M Lim, MBBS, FRACP, PhD, Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2023
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant; immunotherapy; single-cell sequencing; molecular profiling; cemiplimab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: HREC/88736/PMCC-2022-326880

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes