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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Mycosis Fungoides
• Intervention / Treatment: Combination product: Pembrolizumab administered using the Sofusa® DoseConnect™

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Andreas G Niethammer, MD PhD; Phone Number: +18583494820; Email: ANiethammer@Sorrentotherapeutics.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Melissa Banez; Phone Number: 626-218-8276; Email: mbanez@coh.org
      • Principal Investigator: Christiane Querfeld, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All participants; Pembrolizumab administered intralymphatically using the Sofusa® DoseConnect™device	Combination product: Pembrolizumab administered using the Sofusa® DoseConnect™; pembrolizumab will be administered intralymphatically using the Sofusa® DoseConnect™ device; Other Names: Keytruda® administered using Sofusa® DoseConnect™ device

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.
• Investigators: Study Director: Andreas G Niethammer, MD PhD, Sorrento Therapeutics, Inc.

Publications and helpful links

General Publications

• Narducci MG, Tosi A, Frezzolini A, Scala E, Passarelli F, Bonmassar L, Monopoli A, Accetturi MP, Cantonetti M, Antonini Cappellini GC, De Galitiis F, Rosato A, Picozza M, Russo G, D'Atri S. Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab. Front Immunol. 2020 Sep 25;11:579894. doi: 10.3389/fimmu.2020.579894. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Anticipated): January 29, 2024
• Study Completion (Anticipated): March 27, 2024

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: PD-L1; pembrolizumab; CTCL; Mycosis Fungoides; Cutaneous T-cell Lymphoma; MF/SS
• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: STI-SOFUSA-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes