Vaccination against PD-L1 in basal cell carcinoma - a phase IIa trial to assess immunologic effect.

Phase 1

• Conditions: basal cell carcinoma; MedDRA version: 20.0Level: LLTClassification code 10007286Term: Carcinoma basal cellSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002605-62-DK
• Lead Sponsor: Herlev and Gentofte Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-06
• Last Update Posted: 14 June 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Age = 18
At least 1 histological verified superficial or nodular basal cell carcinoma on the body or limbs of bigger than 14 mm in the longest diameter
Willing to provide three 3 mm biopsies from the lesion/lesions
Not previously treated with a hedgehog pathway inhibitor or retinoids
ECOG performance score 0-1
For women: Agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 26 weeks after the treatment.
For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm
Understand and be willing to sign written informed consent after oral and written information about the protocol.
Sufficient bone marrow function, i.e.
Leucocytes = 1,5 x 109
Granulocytes = 1,0 x 109
Thrombocytes = 20 x 109
Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l
Sufficient liver function, i.e.
ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/lBilirubin < 30 U/l

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
The patient has a history of severe clinical autoimmune disease
The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
The patient is pregnant or breastfeeding
The patient is unable to voluntarily agree to participate by signed informed consent or assent
The patient has an active infection requiring systemic therapy
The patient has received a live virus vaccine within 30 days of planned start of therapy
Known side effects to Montanide ISA-51
Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus
Concurrent treatment with other experimental drugs
Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
Severe allergy or anaphylactic reactions earlier in life.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: <br>The aim of the phase 1 study is to investigate overall response rate and immunogenicity after vaccination with PD-L1 in patients with basal cell carcinoma <br><br>;Secondary Objective: Assess the immunologic response to vaccination with PD-L1 peptide i perifial blood and biopsies before, during and after vaccination ;Primary end point(s): Disease control rate (DCR) defined as complete response (CR), partial response (PR), or stable disease (SD) of target lesion after 6 treatments with IO103. Rate of patients with CR, PR and SD.<br>Objective and relative (%) reduction of the largest diameter of target lesion after 6 treatments with IO103.<br>;Timepoint(s) of evaluation of this end point: Baseline, then after second and sixth vaccination and during follow up

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Immune responses in biopsies from basal cell carcinomas (BCC) after treatment with IO103. <br>Immune responses in skin delayed type hypersensitivity (DTH) <br>Incidence of treatment emergent adverse events safety and tolerability)<br>;Timepoint(s) of evaluation of this end point: Blood samples (around 110mL per sample) will be taken at baseline (immediately before the 1st vaccination) and immediately before the 6th vaccination for isolation of PBMC and serum.<br>A tumor biopsy will be obtained at baseline (screening) and after 2 and 6 vaccinations.