Lenalidomide and Cosibelimab for the Treatment of Relapsed/Refractory Mycosis Fungoides or Sézary Syndrome

A Phase 1 Study of Cosibelimab (CK-301; UNLOXCYT) in Combination With Lenalidomide in Patients With Relapsed/Refractory Mycosis Fungoides or Sézary Syndrome

This phase I trial tests the safety, side effects and best dose of lenalidomide in combination with cosibelimab for the treatment of patients with mycosis fungoides or Sézary syndrome that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory).Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Immunotherapy with monoclonal antibodies, such as cosibelimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide in combination with cosibelimab may be safe and tolerable in treating patients with relapsed or refractory mycosis fungoides or Sézary syndrome.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8; Recurrent Mycosis Fungoides; Refractory Mycosis Fungoides; Recurrent Sezary Syndrome; Refractory Sezary Syndrome; Recurrent Transformed Mycosis Fungoides; Refractory Transformed Mycosis Fungoides
• Intervention / Treatment: Drug: Lenalidomide; Procedure: Biospecimen Collection; Other: Questionnaire Administration; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Cosibelimab; Procedure: Skin Biopsy

Detailed Description

PRIMARY OBJECTIVE:

I. Obtain a preliminary estimate of the safety and tolerability of the combination of cosibelimab with lenalidomide in patients with relapsed/refractory (R/R) mycosis fungoides (MF) or Sézary Syndrome (SS).

SECONDARY OBJECTIVE:

I. Obtain a preliminary estimate of the efficacy of the combination of cosibelimab with lenalidomide in patients with relapsed/refractory (R/R) mycosis fungoides (MF) or Sézary Syndrome (SS), as assessed by overall response rate (ORR), complete response (CR) rate, time to response, duration of response, sustained response (ORR4), progression-free survival, and overall survival.

EXPLORATORY OBJECTIVES:

I. To obtain a preliminary assessment of quality of life (QoL) parameters before, during and after the regimen.

II. To evaluate the anti-tumor and immunomodulatory effects in the tumor microenvironment in skin and blood samples of patients with R/R MF or SS treated with combination cosibelimab and lenalidomide.

OUTLINE: This is a dose-escalation study of lenalidomide in combination with fixed dose cosibelimab followed by a dose-expansion study.

Patients receive cosibelimab intravenously (IV) over 1 hour on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan with or without positron emission tomography (PET) at baseline and may undergo CT scan with or without PET scan throughout the trial. Patients undergo skin biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30, 60, and 90 days then every 2 months until progression or initiation of a new therapy (for patients without progression) or every 6 months for patients in survival follow up.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Christiane Querfeld
      • Contact: Christiane Querfeld; Phone Number: 626-218-2405; Email: cquerfeld@coh.org

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:

• Documented informed consent of the participant and/or legally authorized representative.

  • Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  • If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) 0-2

• Ability to read and understand English for questionnaires

• Female patients of childbearing potential must have a negative pregnancy test within 24 hours of dosing

• Histologically confirmed mycosis fungoides (MF)/ Sezary syndrome (SS) including transformed MF, stage IB or higher

  • Stage of disease according to tumor, node, metastasis, blood (TNMB) classification.
  • Pathology report must be diagnostic or be consistent with MF/SS criteria
  • SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria.
  • For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that been recommended by the International Society for Cutaneous Lymphomas (ISCL) should be used

• Have received 1 prior line of systemic therapy (if non-transformed MF)

• Relapsed/ refractory disease

• Measurable disease per Modified Severity Weighted Assessment Tool (mSWAT) and/ or circulating Sezary cell count (Olsen et al. criteria), nodal disease per Lugano

• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy

• Platelets ≥ 75,000/µL. If patient is on full-dose anticoagulation, platelets ≥ 100,000/µL are required

• Hemoglobin ≥ 9g/dL

  • NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement

• Total bilirubin < 2.2 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 x ULN

• Alanine aminotransferase (ALT) ≤ 2.5 x ULN

• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 (as calculated using the Cockcroft-Gault formula) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 (as calculated using the Cockcroft-Gault formula)

• If not receiving anticoagulants: activated partial thromboplastin time (aPTT) ≤ 1.3 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants

• International normalized ratio (INR) < 2.5

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within 24 hours of dosing. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females of childbearing potential to use an effective method of birth control (i.e., failure rate of < 1% per year described below) or abstain from heterosexual activity, and agree to refrain from donating eggs for the course of the study treatment period through at least 30 days after the last dose of lenalidomide, or 4 months after the last dose of cosibelimab whichever is longer

  • A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations).

  • Highly effective methods include:

    • Bilateral tubal ligation
    • Partner's vasectomy (if medically confirmed there are no live sperm and sole sexual partner)
    • Hormonal (stopping ovulation with two drugs [estrogen and progesterone]: oral, within the vagina, or on/under the skin; stopping ovulation with one drug progesterone-only: oral, injected, or on/under the skin).
    • Intrauterine hormone-releasing system (IUS)
    • Intrauterine device (IUD)

  • Hormonal contraceptive methods must be supplemented by a barrier method

    • Barrier methods:

      • Male latex or synthetic condom
      • Diaphragm
      • Cervical Cap

• Agreement by males to either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a female of childbearing potential, and to agree to refrain from donating sperm for the course of the study treatment period through at least 90 days after the last dose lenalidomide, or 4 months after the last dose of tocilizumab (if applicable) whichever is longer

  • All study participants must be registered into the mandatory revlimid Risk Evaluation and Mitigation Strategies (REMS®) program and be willing and able to comply with the requirements of the REMS® program (including use of aspirin [ASA]/Food and Drug Administration [FDA] approved blood thinner).
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the revlimid REMS® program

Exclusion Criteria:

• Prior therapy with immune checkpoint inhibitors, cell-based therapies, or cancer vaccines

• Thalidomide, lenalidomide, or immunomodulatory imide drug (IMiDS) exposure

• Any skin-directed therapy within 14 days prior to initiating protocol therapy

• Any radiation therapy within 21 days prior to initiating protocol therapy

• Prior stem cell transplantation

• Unstable cardiac disease, as defined by one of the following:

  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • NYHA (New York Heart Association) heart failure class III-IV
  • Uncontrolled atrial fibrillation or hypertension

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents

• Clinically significant uncontrolled illness

• Active infection requiring antibiotics

• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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: Treatment (cosibelimab and lenalidomide); Patients receive cosibelimab IV over 1 hour on day 1 and lenalidomide PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan with or without PET scan at baseline and may undergo CT scan with or without PET scan throughout the trial. Patients undergo skin biopsy and blood sample collection throughout the study.

Drug: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501; CC 5013; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Questionnaire Administration; Ancillary studies; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Drug: Cosibelimab; Given IV; Other Names: CK-301; Cosibelimab-ipdl; Anti-PD-L1 Monoclonal Antibody TG-1501; Anti-PDL1 Monoclonal Antibody TG-1501; CK 301; CK301; TG 1501; TG-1501; TG1501; Unloxcyt; Procedure: Skin Biopsy; Undergo skin biopsy; Other Names: Biopsy of Skin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLT)	Defined as any of the following toxicity that occur during the first 3 cycles of treatment, and that are attributed as possibly, probably, or definitely related to protocol therapy. Toxicities include immune related toxicities, hematologic toxicities, specific non hematologic toxicities, any toxicity that would, in the opinion of the principal investigator, prevent continued administration of the combination treatment, or any toxicity that prevents the planned dose escalation of lenalidomide in cycles 1-3. DLT (if any) will be individually described.	From baseline, up to completion of cycle 3 (cycle length = 21 days)
Incidence of adverse events	Toxicities will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0. Observed toxicities will be summarized by type, severity, time of onset, and attribution.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response	Defined as a response-evaluable patient achieving a documented complete response (CR) or partial response (PR) after start of protocol therapy and prior to progression/relapse/start of non-protocol anti-lymphoma treatment. Exact 95% confidence intervals will be calculated.	Up to 1 year
Complete response	Defined as a response-evaluable patient achieving a documented CR after start of protocol therapy and prior to progression/relapse/start of non-protocol anti-lymphoma treatment. Exact 95% confidence intervals will be calculated.	Up to 1 year
Time to response	Will be summarized descriptively.	From initiation of study therapy to the first achievement of CR or PR prior to progression/relapse/start of non-protocol anti-lymphoma treatment, up to 1 year
Sustained response	Defined as a response-evaluable patient achieving an objective response (CR/PR) that lasts at least 4 months prior to progression/relapse/start of non-protocol anti-lymphoma treatment. Exact 95% confidence intervals will be calculated.	Up to 1 year
Duration of response	Will be estimated using the product-limit method of Kaplan and Meier.	From the first achievement of PR or CR to time of progression/relapse or death, up to 1 year
Progression free survival	Will be estimated using the product-limit method of Kaplan and Meier.	From initiation of study therapy to disease relapse/progression or death from any cause, up to 1 year
Overall survival	Will be estimated using the product-limit method of Kaplan and Meier.	From initiation of study therapy to death from any cause, up to 1 year

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Christiane Querfeld, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 16, 2027
• Primary Completion (Estimated): May 16, 2028
• Study Completion (Estimated): May 16, 2028

Study Registration Dates

• First Submitted: November 3, 2026
• First Submitted That Met QC Criteria: November 3, 2026
• First Posted (Actual): November 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 3, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Mycosis Fungoides; Sezary Syndrome; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Carboxylic Acids; Piperidines; Chemistry Techniques, Analytical; Spectrum Analysis; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 260028; P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-07625 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 260028 (Other Identifier: City of Hope Medical Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No