Klinische Studien

Institut
Dermatologie

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Joachim Dissemond

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstr 55
45147 Essen

Sponsor

Boehringer Ingelheim Pharma GmbH & Co. KG

Einschlusskriterien
1. Adult trial participants, aged ?18 years (if local legislation for age of consent differs, then local legislation will be followed) at screening.
2. Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
3. A confirmed diagnosis of ulcerative pyoderma gangrenosum (PG) (?10 points on the PARACELSUS score) that requires systemic therapy in the opinion of the investigator. The diagnosis needs to be confirmed by an Adjudication Committee. Trial participants with mixed PG subtypes are eligible as long as the target lesion is of the ulcerative subtype.
4. At least one measurable (defined as measuring ?5 cm^2) PG ulcer. In trial participants with more than one PG ulcer, the target PG ulcer will be selected by the investigator and confirmed by external Adjudication Committee.
5. At the time of the Screening Visit, a maximum duration of 6 months since the target ulcer in the current PG episode was diagnosed. Target ulcers >6 months since diagnosis are allowed if they are active and progressing, as judged by the investigator and confirmed by an Adjudication Committee.
6. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of use is provided in the participant information and in the protocol.

Ausschlusskriterien
1. Trial participants with non-PG lesions.
2. Trial participants with a target PG ulcer measuring >80 cm^2.
3. Trial participants with chronic, non-inflamed PG wounds or ulcers that are not responsive to immunosuppressive therapy, as determined by an Adjudication Committee.
4. Presence of active ulcer infection at the Screening Visit (unless treated and resolved prior to administration of the first dose of trial medication) based on investigator assessment.
5. Presence of persistent or recurring bacterial infection requiring systemic antibiotic therapy; or clinically significant viral, fungal, or parasitic infections within 2 weeks prior to the Screening Visit. Any such infection must be resolved, with treatment completed ?2 weeks prior to the Screening Visit. No new/recurrent infections should have occurred prior to Visit 2.
6. Active or latent tuberculosis (TB)
o Participants with active TB are excluded
o Participants with latent TB may be included if treatment of latent TB, as per local guidelines, is initiated prior to randomization and completed during the course of the trial."
7. Chronic or acute infections including Human immunodeficiency virus (HIV) infections and viral hepatitis (including occult hepatitis); the corresponding laboratory tests will be performed during screening. A trial participant can be re-screened if the trial participant was treated and is cured from the acute infection.
8. Severe, progressive, or uncontrolled hepatic disease, defined as >3x Upper Limit of Normal (ULN) elevation in Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) or alkaline phosphatase, or >2x ULN elevation in total bilirubin.
Further exclusion criteria apply.

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Pyoderma gangraenosum (PG)

Medizinischer Befund
Pyoderma gangraenosum (PG)

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Lisa Zimmer

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstr 55
45147 Essen

Sponsor

Universitätsklinikum Regensburg

Indikation
Melanom

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Immatics US Inc.

Einschlusskriterien
• Pathologically confirmed and documented cutaneous melanoma- CM patients (including acral melanoma) with unresectable or metastatic disease
• HLA-A*02:01 positive
• Adequate selected organ function per protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor, applied either as monotherapy or in combination with other therapies as treatment for unresectable or metastatic cutaneous melanoma
• Patients with BRAF mutation should have been treated with one prior line of BRAF-directed therapy (with or without a MEK inhibitor) prior to initial eligibility assessment, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition, prior toxicity, or if declined by the patient
• Life expectancy more than 6 months
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• Female patient of childbearing potential must use adequate contraception from randomization until 12 months after the infusion of IMA203 or in line with the instructions provided for investigator's choice treatment (in the control arm)
• Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203 or in line with the instructions provided for investigator's choice treatment (in the control arm)
• The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to randomization.

Ausschlusskriterien
• Primary mucosal or uveal melanoma and melanoma of unknown primary
• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
• Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents.
• History of cardiac conditions as per protocol
• Prior allogenic stem cell transplantation or solid organ transplantation
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
• History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
• History of hypersensitivity to CY, FLU, or IL-2 or presence of any contraindications and other limitations for planned treatment with investigator's choice as laid down in the current versions of the respective PIs / SmPCs
• Known hypersensitivity to any of the rescue medications
• History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the investigator
• Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Any condition contraindicating leukapheresis
• Pregnant or breastfeeding
• Any other condition that would, in the investigator's or sponsor's judgment, contraindicate the patient's participation in the clinical trial because of safety concerns or compliance with clinical trial procedures (e.g., psychiatric disorders or substance dependence, neurological impairment)
• Patient has received systemic corticosteroids within 2 weeks prior to leukapheresis,
• Patient has received surgery or other anti-cancer therapies, any agent that is likely to suppress bone marrow function, or investigational medicinal products within 7 days prior to leukapheresis.
• Patients with any active infection or ongoing reactivation of infection
• Patients who underwent non-myeloablative lymphodepletion prior to cell therapy within the last 6 months
• Prior treatment with IMA203
• Patients with ascites, pleural or pericardial effusion which requires repeated (2 within 4 weeks) or continuous paracentesis, thoracentesis or pericardiocentesis within last 2 months
• Patients with LDH greater than 2.0-fold ULN
• Concurrent treatment in another clinical trial or a device study that could interfere with the IMA203 treatment or planned investigator's choice treatment
• Patients with active brain metastases or leptomeningeal metastases
• Patient has received any investigational therapies, inactivated vaccines, chronic use of systemic corticosteroids or IV antibiotics within 1 week prior to randomization, or live vaccines within 4 weeks prior to randomization
• Patient has received any anti-cancer therapy (prior anti-cancer treatment or bridging therapy) or radiotherapy within 1 week prior to start of trial treatment
• Other protocol defined inclusion/exclusion criteria could apply

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Melanom

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

immatics biotechnologies GmbH, Tübingen

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Refractory Cancer\nRecurrent Cancer\nSolid Tumor, Adult\nCancer

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Immunocore Limited, UK

Einschlusskriterien
- Participants must be HLA-A*02:01-positive
- Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma
- Archived or fresh tumor tissue sample that must be confirmed as adequate
- Participants must have measurable disease per RECIST 1.1
- Participant must have BRAF V600 mutation status determined
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention

Ausschlusskriterien
- Participants with a history of a malignant disease other than those being treated in this study
- Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
- Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients
- Participants with clinically significant pulmonary disease or impaired lung function
- Participants with clinically significant cardiac disease or impaired cardiac function
- Participants with active autoimmune disease requiring immunosuppressive treatment
- Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
- Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma
- Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3

Studienteilnehmende Mindestalter
Jahr(e)

Indikation
Melanom

Medizinischer Befund
Advanced melanoma

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Immunocore Limited, UK

Einschlusskriterien
- HLA-A*02:01-positive.
- unresectable Stage III or Stage IV non-ocular melanoma
- archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not previously irradiated has been provided.
- measurable or non-measurable disease per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- If applicable, must agree to use highly effective contraception
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol

Ausschlusskriterien
- Pregnant or lactating women
- diagnosis of ocular or metastatic uveal melanoma
- history of a malignant disease other than those being treated in this study
- ineligible to be retreated with pembrolizumab due to a treatment-related AE
- known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
- previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
-active autoimmune disease requiring immunosuppressive treatment
- clinically significant medical condition
- known psychiatric or substance abuse disorders
- received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication
- received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb, ipilimumab, and BRAF TKI regimen) within 14 days of first dose
- received cellular therapies within 90 days of first dose
- received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of first dose
- have not progressed on treatment with an anti-PD(L)1 mAb
- have not received prior ipilimumab
- a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen
- currently participating or have participated in a study of an investigational agent or using an investigational device within 30 days of the first dose
- known history of chronic viral infections
- Out of range Laboratory values
- history of allogenic tissue/solid organ transplant

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Advanced Melanoma

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
• Males or females =18 years of age who have provided written informed consent prior to completing any study-specific procedure. For Arm 2d, participants =12 years are eligible with informed consent/assent.
• Dose Escalation (Arm 1a): Participant has histologically confirmed locally advanced or metastatic cancer (cutaneous melanoma, NSCLC, non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, microsatellite stable colorectal cancer [MSS CRC], basal cell carcinoma, or triple negative breast cancer) with measurable disease as determined by RECIST v1.1. Arm 1a participants must have received, and then progressed, relapsed, or been intolerant to, or ineligible for, at least 1 standard treatment regimen in the advanced or metastatic setting. Participants with a known driver mutation must have also received or been offered a mutation-directed therapy, where indicated. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
• Dose Confirmation (Arm 1b): Participant has histologically confirmed locally advanced or metastatic, and CPI refractory melanoma or locally advanced or metastatic, and CPI refractory NSCLC with measurable disease as determined by RECIST v1.1 who has disease progression after, at least 1 line of standard therapy (no limit to prior lines of therapy), and has been treated with or refused standard of care treatment. Participants in PD arm Group 2 must also have PD-L1 TPS =1%. Participants must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Primary refractory is defined as prior exposure to anti-programmed death-1 (PD-1)/PD-L1 antibody for at least 6 weeks but no more than 6 months with demonstration of progression on 2 separate scans at least 4 weeks apart but no more than 12 weeks apart and progression occurring within 6 months after first dose of anti-PD-1 antibody. Acquired secondary resistance must have confirmed objective response or prolonged stable disease (SD) (>6 months), followed by disease progression in the setting of ongoing treatment and confirmed progression on scans at least 4 weeks apart. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
1. For NSCLC participants with known EGFR, ALK, proto-oncogene tyrosine-protein kinase reactive oxygen species (ROS1), or other actionable mutations for which there are approved targeted therapies, participants must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.
2. Expansion of the melanoma Arm 1b cohort (up to approximately 16 additional evaluable participants) will require prospective central testing of Screening tumor biopsies to confirm PD-L1 TPS =1% for eligibility.
• Dose Expansion Arms (Arm 2): Participant has histologically confirmed:
1. Arm 2a: Locally advanced or metastatic melanoma who have not yet received any prior systemic therapy for their melanoma in this setting.
2. Arm 2b: Newly diagnosed locally advanced or metastatic NSCLC with a PD-L1 TPS of =50% with no known EGFR or ALK positive tumor mutations who have not yet received any prior systemic therapy for their NSCLC (that is, treatment-naive).
3. Arm 2c: Locally advanced or metastatic melanoma in participants who have not received prior systemic therapy for melanoma in the advanced/metastatic setting.
4. Arm 2d: Advanced/metastatic melanoma that is CPI refractory and having a centrally confirmed PD-L1 TPS of =1% on their Screening tumor biopsy.
• All participants must have measurable disease as determined by RECIST v1.1.
• Participants must have a tumor lesion amenable to biopsy and must provide tumor biopsy sample at baseline (archival formalin-fixed, paraffin-embedded [FFPE] tissue collected within 90 days of informed consent is accepted as long as no intervening therapy is received, during this time), and optionally at all on-treatment timepoints (including response or progression) if medically feasible. Participants in Arm 2c: Sufficient tumor tissue (slides or FFPE block) for PD-L1 testing is required as per Laboratory Manual. Participants in Arm 2c may be replaced in this cohort if not PD-L1 evaluable. Participants in Arm 1b melanoma expansion cohort and Arm 2d: Central confirmation of PD-L1 TPS score is required prior to enrollment.
• If the participant is undergoing a new biopsy, they must have another lesion outside of the lesion biopsied at baseline that can be followed as a RECIST v1.1 target lesion for response.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of =1.
• Participant has adequate hematological and biological function.

Ausschlusskriterien
• Participant has active central nervous system tumors or metastases.
• Participant has received treatment with prohibited medications (that is, concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor], hormonal anticancer treatment, biologic therapy, or immunotherapy) or investigational agents within 5 half-lives or 14 days prior to the first day of study treatment, whichever is shorter. Prior exposure to any investigational or approved agent designed to simultaneously target both indoleamine 2,3-dioxygenase (IDO1) and PD-L1 is also exclusionary.
• Participant has required the use of additional immunosuppression (for example, infliximab) other than corticosteroids for the management of an AE, has experienced recurrence of an AE if rechallenged, and currently requires maintenance doses of >10 milligrams (mg) prednisone or equivalent per day.
• Participant has any plan to receive a live attenuated vaccine during study treatment or has received a live vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines and non-live coronavirus disease 2019 (COVID-19) for injection are generally allowed.
• Participant has reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Grade ?2 from previous anticancer therapy with the exception of alopecia, vitiligo, and prespecified laboratory values.
• Participant who is pregnant, breastfeeding, or is of childbearing potential, defined as those who are capable of becoming pregnant who are not willing to employ a highly effective method of contraception during dosing and for 90 days after the last dose of mRNA-4359 or 4 months after the last dose of pembrolizumab or 5 months after the last dose of ipilimumab/nivolumab administrations, whichever is longer.
• Sexually active participants who refuse to use a condom during intercourse or participants who will not refrain from sperm donation while taking study treatment and for 90 days after the last dose of mRNA-4359 or 4 months after the last dose of pembrolizumab or 5 months after the last dose ipilimumab/nivolumab, whichever is longer, or who will not refrain from sperm donation for the same time period.
• Participant has any unstable or clinically significant concurrent medical condition (for example, substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism) that would, in the opinion of the Investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol. Also including but not limited to, ongoing or active infection, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, active gastrointestinal bleeding or hemoptysis or history of bleeding disorder, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent.
• Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study).

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Solide Tumoren

Medizinischer Befund
Advanced Solid Tumors

Institut
Dermatologie

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Joachim Dissemond

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstr 55
45147 Essen

Einschlusskriterien
* Diagnosed leg Ulcer of vascular origin (venous or mixed venous-arterial) without severe arterial insufficiency. Diagnosis of leg ulcer is based on angiological tests carried out at a given time, regardless of whether it is recent or older.
* Ulcer area between 2 - 50 cm2 after debridement
* Patients are older than 18 years of age.
* Chronic ulcer(s) with duration greater than 30 days and less than 2 years (continuous duration)
* If more than one ulcer is present, the target ulcer may be chosen based on the investigator's preference. However, the target ulcer must have a spatial distance of at least 5cm from all other ulcers so that measurements can be carried out accurately even in case an ulcer is growing in size.
+ For diabetic patients: well-controlled diabetic mellitus (HbA1c = 8%, historical results <3 months is acceptable)
* Adequate vascular perfusion as evidence by: ABI > 0.5 and < 1.30, ankle artery pressure >60 mmHg (historical results <3 months is acceptable).
* Women of childbearing age must agree to use adequate method of contraception
* Informed consent as documented by signature of the participant or a LAR, and being able to understand German or French language and follow the study protocol (cognition)

Ausschlusskriterien
* Women who are pregnant or breastfeeding (Women of childbearing potential need to perform a pregnancy test (urine test) within 24 hours prior to the study intervention and need at least one simple acceptable contraceptive method)
* Suspected skin cancer, or documented history of skin cancer or any other localized cancer, precancerous lesions or large moles in the areas to be treated.
* Use of photosensitizing agents or medications
* The patient is undergoing severe endogenous or drug immunosuppression
* Decompensated heart failure (NYHA III-IV)
* Patient with chronic renal insufficiency currently undergoing dialysis.
* Wounds with >30% wound area reduction in the last 2 weeks while receiving optimal standard of care (SOC) prior to randomization
* The patient is receiving systemic antibiotic treatment or is receiving/needing antibiotic wound therapy in/near the wound at inclusion
* The patient has received one of the following treatments in the last 2 weeks:
- Arterial interventions such as angioplasty or vascular surgery. Venous Interventions including venous angioplasty, sclerotherapy, stenting, or endovenous thermal or non-thermal ablation.
* Cell and tissue based therapies such as punch & skin grafts in general, placental based allografts, autologous skin substitutes, cellular and acellular dermal matrix, platelet rich plasma and stem cell therapies
* Advanced wound care therapies such as shock wave, cold plasma, electric stimulation, ultrasound, negative pressure wound therapy, nanotechnologies, oxygen therapies
* Participants that were previously included in this clinical trial

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse

Medizinischer Befund
Venous Leg Ulcer\nWound Heal\nMagnetic Field Exposure

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Geschlecht
Divers, Männlich, Weiblich

Indikation
MCC - Merkelzellkarzinom, Non-melanoma skin cancer (NMSC)

Medizinischer Befund
Merkel cell carcinoma

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Philogen S.p.A, Italien

Geschlecht
Divers, Männlich, Weiblich

Indikation
Non-melanoma skin cancer (NMSC)

Medizinischer Befund
Cutaneous Squamous Cell Carcinoma

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Philogen S.p.A, Italien

Geschlecht
Divers, Männlich, Weiblich

Indikation
Non-melanoma skin cancer (NMSC)

Medizinischer Befund
Basal cell carcinoma of skin

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Philogen S.p.A, Italien

Geschlecht
Divers, Männlich, Weiblich

Indikation
Non-melanoma skin cancer (NMSC)

Medizinischer Befund
Basal cell carcinoma

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Philogen S.p.A, Italien

Einschlusskriterien
1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
2. Be > or equal to 18 years of age on day of signing informed consent.
3. Participant with histologically or cytologically confirmed diagnosis of unresectable metastatic melanoma at stage III B, C, D or IV M1a (AJCC 8th ed.). Patients with Stage IVM1b, M1c and M1d oligometastatic disease [up to 10 lesions in aggregate including lung, liver, bone or brain, with or without lymph node involvement], are eligible. However, patients with symptomatic or rapidly enlarging/bleeding brain lesions are excluded. Patients with acral lentiginous melanoma are eligible as well. Detailed information about prior therapies and burden of disease at study entry must be available.
4. Patients must have confirmed primary resistance to or acquired resistance on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
a.) Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
b.) Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
c.) Progressive disease has been documented within 12 weeks from the last dose of anti- PD-1/L1 mAb.
i. Progressive disease is determined according to iRECIST.
ii. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
5. Patients harboring the BRAF mutation who received BRAF/MEK inhibition (or declined BRAF/MEK inhibitors) and received thereafter anti-PD1 therapy showing resistance to such immunotherapy are eligible to the study. Anti-PD1 immunotherapy must be the last therapy received by the patient prior to randomization.
6. Eligible subjects must have measurable disease (according to RECIST v1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Eligible subjects must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal metastatic melanoma lesion (= 5 mm in longest diameter) or with multiple injectable lesions that in aggregate have a diameter of = 5 mm.
7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) b.) A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. WOCBP must be using for the time period indicated highly effective contraception methods. WOCBP and effective contraception methods are defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP).
8. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the Procedures Manual).
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
10. Have adequate organ function as defined in the following table. Specimens must be collected within 14 days prior to the start of study treatment.
11. Be able to provide a core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening. In addition, participants may provide additional biopsy at Week 18 and at the time of discontinuation due to progression
12. Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (e.g. anti-HBsAg and/or anti-HBc Ab) a negative serum HBV-DNA test is also required.
13. All acute toxic effects (excluding alopecia and vitiligo) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v. 5.0) Grade = 1 or baseline unless otherwise specified above. Note: Participants with =Grade ß neuropathy may be eligible. Participants with endocrinerelated AEs Grade =ß requiring treatment or hormone replacement may be eligible. Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
14. Full resolution of checkpoint blockade therapy-related adverse effects (including immunerelated adverse effects) and no treatment for these AEs for at least 4 weeks prior to the time of enrollment.
15. No history of severe immune related adverse effects from prior given immune checkpoint blockade therapy (CTCAE Grade 4; CTCAE Grade 3 requiring treatment >4 weeks).
16. Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration. In addition, male participant must refrain from sperm donation during the treatment period.
17. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Ausschlusskriterien
Medical Conditions
1. Patients with more than 10 distant melanoma lesions in lung, liver, bone or brain combined. Patients with symptomatic or rapidly enlarging/bleeding brain lesions are excluded.
2. Uveal melanoma or mucosal melanoma or melanoma with unknown primary.
Pregnancy Exclusion
3. A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Prior/Concomitant Therapy
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.
5. Has received prior systemic anti-cancer therapy including investigational agents or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
6. Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (?? weeks of radiotherapy) to non-CNS disease.
7. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD).
8. Has had an allogeneic tissue/solid organ transplant.
9. Has received live live or live attenuated vaccines within 30 days prior to the first dose of study treatment and while participating in the study. Note: Killed vaccines are allowed. Note: Any licensed COVID-19 vaccine (including for Emergency use) in a particular country is allowed in the study as long as they are mRNA vaccines, adenoviral vaccines, or inactivated vaccines. These vaccines will be treated just as any other concomitant therapy. Investigational vaccines (i.e., those not licensed or approved for Emergency Use) are not allowed.
Diagnostic assessments
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment within the past two (2) years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), second primary melanoma in situ, or carcinoma in situ, that have undergone potentially curative therapy are not excluded.
12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
13. Has severe hypersensitivity (?Grade ?) to pembrolizumab and/or any of its excipients, or to (immuno)cytokines IL2, TNF and/or any of its excipients
14. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
15. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
16. Has an active infection requiring systemic therapy.
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
18. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
19. Previous enrolment and randomization in this same study.

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Melanoma Stage III\nMelanoma Stage IV

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Replimune, Inc. USA

Einschlusskriterien
Key Inclusion Criteria:
• Male or female who is 12 years of age or older at the time of signed informed consent.
• Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma.
• Confirmed disease progression (PD) on an approved anti-PD-1 and an anti-CTLA-4 treatment, administered either as a combination regimen (eg, nivolumab + ipilimumab) or in sequence.
1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks
2. Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody are eligible
• Has documented BRAF V600 mutation status. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to enrollment in the study, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity.
• Has at least 1 measurable and injectable tumor of =1 cm in longest diameter (or shortest diameter for lymph nodes).
• Has adequate hematologic function.
• Has adequate hepatic function.
• Has adequate renal function.
• Prothrombin time (PT) =1.5 × ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =1.5 × ULN
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 for patients 18 years and older or a Lansky performance score (PSc) =80 for patients 12 to 17 years of age.
• Life expectancy of at least 3 months.
• Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of study treatment.
• Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-hCG) test within 72 hours before the first dose of study treatment.

Ausschlusskriterien
Key Exclusion Criteria:
• Primary mucosal or uveal melanoma.
• More than 2 lines of systemic therapy for advanced melanoma.
• Known acute or chronic hepatitis.
• Known human immunodeficiency virus (HIV) infection.
• Active significant herpetic infections or prior complications of HSV-1 infection.
• Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to dosing.
• With active significant herpetic infections or prior complications of HSV-1 infection.
• Evidence of spinal cord compression or at high risk of spinal cord compression.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening.
• Serum lactate dehydrogenase (LDH) >2 × ULN.
• Major surgery ?2 weeks prior to starting study drug.
• Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured
• History of significant cardiac disease including myocarditis or congestive heart.
• History of life-threatening toxicity related to prior immune.
• Active, known, or suspected autoimmune disease requiring systemic treatment.
• History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
• Prior oncolytic virus or other therapy given by intratumoral administration.
• Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
• Has received a live vaccine within 28 days prior to the first dose of study treatment.
• Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.
• Conditions requiring treatment with immunosuppressive doses (>10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Advanced Melanoma

Institut
Dermatologie

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Frederik Krefting

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstr. 55
45147 Essen

Einschlusskriterien
• Confirmed acute scabies disease: Detection of mites and/or mite nymphs and/or mite larvae, by reflected light microscopy or light microscopy of skin samples, at scabies-typical predilection sites
• Age between 2 years and 85 years
• Written informed consent of the study participant (if of legal age) or all legal guardians (for underage study participants < 12 years) or all legal guardians and the study participant (for underage study participants ? 12 years)
• Practicable application of the trial medication by trained specialist staff at the trial site

Ausschlusskriterien
• Pre-treatment with antiscabiosa in the last 14 days
• Combined antiscabial treatment (i.e. simultaneous/simultaneous topical and systemic scabies treatment with medication) in the last 3 months
• Known intolerance to permethrin, other pyrethroids, chrysanthemums or any of the other ingredients of the study medication
• Scabies crustosa
• Impetiginization/eczematization requiring inpatient treatment
• Body weight > 120 kg
• Pregnancy, breastfeeding
• Clinically relevant immunodeficiency (of any kind, including extensive local therapy (>20% body surface) with corticosteroids > 2 weeks in the last 4 weeks or ? 10 mg prednisolone equivalent >7 days in the last 4 weeks - even without signs of scabies crustosa)
• Other serious illnesses which, in the opinion of the investigator, prevent the patient from participating in the study
• Planned systemic use of corticosteroids
• Planned or previous (last 4 weeks) use of systemic or cutaneous non-steroidal immunosuppressants
• Apparent unreliability or unwillingness to cooperate
• Inability to understand and comply with study instructions
• Known alcohol, medication or drug dependence
• Placement in a facility where people live together for long periods of time, are cared for or receive medical care, and where close skin-to-skin contact is common, or placement in an institution ordered by a court/authority
• 5 or more close contacts (persons with close, extensive skin-to-skin contact with the scabies patient for more than 5-10 minutes)
• Close contact person who refuses scabies treatment or for whom treatment is not possible
• Dependence on sponsor or investigator
• Previous participation in a clinical trial in the last 30 days or in the same clinical trial

Studienteilnehmende Mindestalter
85 Jahr(e)

Studienteilnehmende Höchstalter
85 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Skabies

Medizinischer Befund
Scabies

Institute
Dermatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Dirk Schadendorf

+49 (0)201 723-2225
Hautklinik.Studienzentrum@uk-essen.de

Hufelandstraße 55
45147 Essen

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Melanom

Medizinischer Befund
Melanom