Clinical trial NCT04118868: Pembrolizumab Administered Via the Sofusa® DoseConnect™ in Patients With Relapsed/Refractory Cutaneous T-cell Lymphoma.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Mycosis Fungoides
Keywords: CTCL
Cutaneous T-cell Lymphoma
MF/SS
Mycosis Fungoides
pembrolizumab
PD-L1
Lead sponsor: Sorrento Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamic effect of pembrolizumab administered by the Sofusa® DoseConnect™ device
timeFrame: Approximately 14 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of pembrolizumab administered by the Sofusa® DoseConnect™ device
timeFrame: Approximately 24 months
measure: Area Under the Curve (AUC) of the blood levels of pembrolizumab
timeFrame: Approximately 17 months
measure: Maximum Plasma Concentration (Cmax) of pembrolizumab
timeFrame: Approximately 17 months
measure: Time of Maximum concentration observed (Tmax) of pembrolizumab
timeFrame: Approximately 17 months
measure: Half-life (t1/2) of pembrolizumab
timeFrame: Approximately 17 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
Study officials:
affiliation: Sorrento Therapeutics, Inc.
name: Andreas G Niethammer, MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.