Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell Carcinomas

Study Overview
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Brief Summary
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The study aim is to assess the immunological and clinical response in basal cell carcinoma (BCC) treated with ablative fractionated laser (AFL) as monotherapy and compare with BCC treated with combination-therapy of AFL and the anti-PD1-drug nivolumab and with nivolumab as monotherapy.

Detailed Description
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Explorative open label study. Patients and investigators are non-blinded and patients not randomized to interventions. Three intervention groups: AFL monotherapy (8-10 patients) AFL+intratumoral nivolumab (8-10 patients) Intratumoral nivolumab monotherapy (8-10 patients) Patients will attend 4 visits Immunological response is determined by immunohistochemistry (IHC) analysis from biopsies taken prior to AFL, AFL+Nivolumab or Nivolumab treatment (baseline) and compared with biopsies 1 week after treatment. Further, comparison of the immunological response of AFL monotherapy with immunological response AFL+Nivolumab and Nivolumab as monotherapy will be performed. Patients included for AFL as monotherapy will after tumor demarcation receive AFL of the BCC including a 5 mm margin. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion/oozing from the treated area. Patients included for AFL+Nivolumab will after tumor demarcation receive AFL of the BCC including a 5 mm margin, immediately followed by intratumoral injection of Nivolumab. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion/oozing form the treated area. Patients included for monotherapy with Nivolumab will after tumor demarcation get an intratumoral injection of Nivolumab. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion from the treated area. All patients will have a final visit at week 15, around 12 weeks after first treatment, where the clinical response will be evaluated, and treated tumor will be treated following national guidelines for treatment of BCCs. For subgroups of clinical responders and non-responders tumor will at week 15 be used for multiplex gene expression analysis via nanostring (Pan cancer immune profiling panel). For all groups, clinical photographs are taken at every study visit. For patients that present with more than one tumor, patients will be invited to participate with all tumors relevant to the study.

Official Title
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Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell

Conditions
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BCC - Basal Cell Carcinoma, Immune Response, Immunotherapy, Ablative Fractionated Laser

Intervention / Treatment
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* Drug: Nivolumab 10 MG/ML
* Device: Ablative fractionated laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years or older Clinical suspicion of BCC or histologically verified BCC at baseline and histologically verified BCC at visit 2, irrespective of histologic subtype with diameter ≥7 mm at baseline. Signed informed consent. Female subjects of childbearing potential* must be confirmed not pregnant by a negative pregnancy test prior to study treatment and must use a safe contraceptive method Exclusion Criteria: Concomitant treatment with 5-FU or imiquimod Concomitant chemotherapeutic treatment Concomitant systemic immunotherapeutic treatment, including Prednisolone Pregnant or lactating women Allergies to anti-PD1 Patients with a tendency to form keloids Other skin diseases or tattoos in the treatment area

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AFL monotherapy<br>Singe dose AFL as monotherapy, 100 mJ | Device: Ablative fractionated laser<br>* Se previously<br>|
| Active Comparator: AFL+nivolumab<br>Single dose AFL 100 mJ followed by immediate intratumoral injection of nivolumab 10% 0.1 ml/cm2 tumor | Drug: Nivolumab 10 MG/ML<br>* Se previously<br>* Other names: opdivo;Device: Ablative fractionated laser<br>* Se previously<br>|
| Active Comparator: nivolumab monotherapy<br>Intratumoral injection of nivolumab 10% 0.1 ml/cm2 tumor | Drug: Nivolumab 10 MG/ML<br>* Se previously<br>* Other names: opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunological response of AFL and nivolumab as monotherapy and AFL+Nivolumab in BCC | IHC as CD8/CD3 ratio CD4+Foxp3+/CD4 ratio | 1 week | 
| investigate the clinical response of AFL and Nivolumab as monotherapy and AFL+Nivolumab in BCC | evaluated by tumor reduction measured in mm and documented by clinical photos | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of AFL, intratumoral nivolumab and AFL+Nivolumab | evaluated as local skin reactions 1 week and 12 weeks after exposure | 12 weeks | 
| Detection of intra-tumoral Nivolumab | evaluated by ELISA with anti-anti-PD1 | 1 week | 
| Analysis and quantification of PD-L1 expression (tumor cells and TILs) | evaluated by IHC | 2 weeks |