Pembrolizumab Administered Via the Sofusa® DoseConnect™ in Patients With Relapsed/Refractory Cutaneous T-cell Lymphoma.

Study Overview
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Brief Summary
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In this pilot study, pembrolizumab will be administered via DoseConnect in patient with relapsed or refractory cutaneous T-cell lymphoma to assess through pharmacodynamic assessment in the tumor tissue to assess if lymphatic delivery of pembrolizumab using Sofusa DoseConnect is feasible.

Detailed Description
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This is an open-label, single-center pilot study to investigate the pharmacodynamics, pharmacokinetics (PK), safety, and activity of pembrolizumab administered intra-lymphatically using the DoseConnect in participants with relapsed or refractory cutaneous T-cell lymphoma (CTCL). All participants will receive the study intervention, pembrolizumab administered intralymphatically using the Sofusa DoseConnect device.

Official Title
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Phase 1B, Pilot Study to Assess the Pharmacodynamics, Pharmacokinetics, Safety, Activity of Pembrolizumab Administered Intra-lymphatically Using the Sofusa® DoseConnect™ in Patients With Relapsed/Refractory Cutaneous T- Cell Lymphoma (CTCL)

Conditions
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Mycosis Fungoides

Intervention / Treatment
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* Combination Product: Pembrolizumab administered using the Sofusa® DoseConnect™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of one of Mycosis fungoides (MF) Stage IB to IIIB disease at screening Received at least 1 previous line of systemic therapy for CTCL. (Participants with CD 30 positive MF must have received prior treatment with brentuximab vedotin.) Documented disease progression during or after the last therapy. Not previously treated with transplant and is ineligible for transplant Willing to undergo two biopsies during the study 18 years or older at the time of signing informed consent form (ICF) Adequate organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Females of childbearing potential (FCBP) must agree to use a reliable form of contraceptive for the duration of the study and for at least 120 days (4 months) following the last dose of study intervention. Male participants must agree to use barrier contraception (i.e., condoms) for the duration of the study and for at least 120 days (4 months) following the last dose of study intervention Exclusion Criteria: Disease with extensive visceral or blood involvement. Previously treated with an anti-PD-L1 or anti-PD-1 antibody Any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo, hormone replacement therapy for stable thyroid diseases and Type 1 diabetes mellitus. Prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. Known seropositive for or have active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), or human immunodeficiency virus (HIV) History of interstitial lung disease History of severe hypersensitivity reactions to other monoclonal antibodies or known hypersensitivity to the study intervention or its excipients, indocyanine green dye or iodine. Known current drug or alcohol abuse. Pregnant or lactating. Underlying medical condition resulting in abnormally slow lymphatic flow as determined by the Investigator. Require immediate treatment for MF

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All participants<br>Pembrolizumab administered intralymphatically using the Sofusa® DoseConnect™device | Combination Product: Pembrolizumab administered using the Sofusa® DoseConnect™<br>* pembrolizumab will be administered intralymphatically using the Sofusa® DoseConnect™ device<br>* Other names: Keytruda® administered using Sofusa® DoseConnect™ device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic effect of pembrolizumab administered by the Sofusa® DoseConnect™ device | T-cell exhaustion/activation markers: PD-1, Lag-3, Tim-3, ICOS, HLA-DR and Granzyme B in CD3+CD4+ malignant and CD3+CD8+ tumor-infiltrating T-cells in tumor tissue | Approximately 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of pembrolizumab administered by the Sofusa® DoseConnect™ device | Terms, frequency, severity and seriousness of adverse events (AEs) and relationship of AEs to pembrolizumab and/or Sofusa® DoseConnect™ | Approximately 24 months | 
| Area Under the Curve (AUC) of the blood levels of pembrolizumab | Measure the actual body exposure to pembrolizumab | Approximately 17 months | 
| Maximum Plasma Concentration (Cmax) of pembrolizumab | Measure the maximum (or peak) blood concentration of pembrolizumab | Approximately 17 months | 
| Time of Maximum concentration observed (Tmax) of pembrolizumab | Measure the is the time at which the maximum blood concentration of pembrolizumab is observed | Approximately 17 months | 
| Half-life (t1/2) of pembrolizumab | Measure the time it takes for the concentration of the pembrolizumab in the blood to be reduced by 50% | Approximately 17 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTCL, Cutaneous T-cell Lymphoma, MF/SS, Mycosis Fungoides, pembrolizumab, PD-L1