E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced or metastatic cutaneous squamous cell carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced squamous cell carcinoma of the skin |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085908 |
E.1.2 | Term | Cutaneous squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to investigate effects of Cemiplimab treatment on cSCC precursors (actinic keratoses (AK)) in patients who receive Cemiplimab as SoC for advanced cutaneous squamous cell carcinoma (cSCC). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate efficacy of Cemiplimab treatment on cSCC.
The translational objective is the characterization of the tumor immunology and biology on response to Cemiplimab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Centrally confirmed histological diagnosis of advanced cutaneous squamous cell carcinoma (cSCC): either locally advanced or metastatic, surgery or radiotherapy not possible, contraindicated or refused by patient. 2. Coexistence of cSCC precursor lesions, i.e. field cancerization larger than 5x5cm and/or at least 6 separate actinic keratosies. 3. Decision to perform medical treatment with PD-1 inhibitor as Standard of Care. 4. 18 years and older. 5. Ability to understand and sign a written informed consent. 6. Expected survival of at least 6 months. 7. ECOG performance status: 0-2. 8. Washout period of at least 2 weeks to prior major surgery, radiotherapy or any previous systemic or local treatment. 9. Adequate laboratory parameters particularly for the blood count, renal and liver function parameters. 10. In female patients: adequate contraception or no childbearing potential. 11. No concomitant use of other approved or investigational antitumor agents. 12. No other serious illnesses, which might impact the outcome of the patient or the uptake of the drug significantly. 13. Patient consents to participate in the translational research project.
|
|
E.4 | Principal exclusion criteria |
1. Current use of immunosuppressive medication, EXCEPT for the following: • Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection). • Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent. • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 2. Prior organ transplantation including allogenic stem-cell transplantation. 3. Active infection requiring systemic therapy. 4. Known history of testing positive for HIV or known acquired immunodeficiency syndrome. 5. Hematological neoplasms including chronic lymphocytic leukemia (CLL). 6. Vaccination with any live vaccine (e.g. intranasal flu vaccine) within 4 weeks before the first dose of PD-1 inhibitor or planned vaccination with live vaccine during the trial 7. Any other systemic anti-tumor therapy in the last 4 weeks. 8. Pregnancy or lactation period. 9. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent. 10. Known alcohol or drug abuse. 11. Legal incapacity or limited legal capacity.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Clinical assessment of the severity of actinic keratoses during PD-1 inhibitior therapy as measure for efficacy. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints • Overall response rate defined as percentage of patients with CR and PR
Translational Endpoints • Induction or boost of intralesional immune responses (as measured by immunohistology, mRNA expression and T-cell receptor repertoire usage analyses; variables will be determined at baseline and under therapy. • Analyses of predictive markers for AK response • Analysis of predictive markers for cSCC response
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Overall response rate at 12 weeks and 24 weeks of cSCC • Translational Endpoints at week 3, 6, 12, 24 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study is defined as the last visit of the last patient within the study period of 24 weeks. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |