Cosibelimab for CSCC in Patients With Kidney Transplant or Hematologic Malignancy

A Phase IV Master Protocol of Cosibelimab in Special Populations With Advanced Cutaneous Squamous Cell Carcinoma (CosiMaster)

This is study is to evaluate the safety and efficacy of cosibelimab in special populations with advanced cutaneous squamous cell carcinoma (CSCC).

The name of the drug involved in this research study is:

-cosibelimab (a type of an anti-PD-L1 antibody)

Study Overview

• Status: Not yet recruiting
• Conditions: Skin Cancer; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cosibelimab; Drug: Prednisone; Drug: Sirolimus; Drug: Everolimus

Detailed Description

This is a Phase IV, multi-site, multi-cohort, open-label clinical trial investigating the safety and efficacy of cosibelimab in special populations with advanced cutaneous squamous cell carcinoma (CSCC). Checkpoint Therapeutics is supporting this research study by providing the study drug, cosibelimab.

Participants will be enrolled into one of two study groups: Group A or Group B.

Cosibelimab is FDA-approved for the treatment of advanced cutaneous squamous cell carcinoma

The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, Computerized Tomography (CT) scans, or Positron Emission (PET) scans, electrocardiograms (ECGs), Tumor biopsies and aspirations.

It is expected that about 80 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ann Silk, MD; Phone Number: 617-632-6836; Email: Ann_Silk@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
      • Principal Investigator: Ann Silk, MD
      • Contact: Ann Silk, MD; Phone Number: 617-632-6836; Email: Ann_Silk@dfci.harvard.edu
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Principal Investigator: Ann Silk, MD
      • Contact: Ann Silk, MD; Phone Number: 617-632-6836; Email: Ann_Silk@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• COHORT A: Participant must have a history of kidney transplant (at least 6 months prior to enrollment). (A history of more than one kidney transplantation is permitted.)
• COHORT B: Participant must have a diagnosis of a hematologic malignancy, including chronic myeloproliferative neoplasm (CMN) or an indolent non-Hodgkin's lymphoma (NHL), or multiple myeloma (MM).

• Examples of indolent non-Hodgkin's lymphomas (NHL), including but not limited to:

  • Chronic lymphocytic leukemia (CLL)
  • Small cell lymphocytic lymphoma (SLL)
  • Follicular lymphoma (FL)
  • Lymphoplasmacytic lymphoma
  • Waldenström macroglobulinemia
  • Marginal zone lymphoma
  • Mantle cell lymphoma, indolent variety
  • Cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)

• Examples of chronic myeloproliferative neoplasms (CMN), including but not limited to:

  • Chronic myelogenous leukemia (CML)
  • Polycythemia vera (PV)
  • Primary myelofibrosis
  • Essential thrombocythemia (ET)
  • Chronic neutrophilic leukemia
  • Chronic eosinophilic leukemia

• Examples of myeloma, including but not limited to:

  • Multiple myeloma (MM)
  • Smoldering myeloma
• Participants must have histologically or cytologically confirmed diagnosis of cutaneous squamous cell carcinoma (CSCC).
• Note: Mixed histology is acceptable (e.g. basosquamous, squamous cell carcinoma with adnexal differentiation), and other histologic variants (sarcomatoid carcinoma, spindle cell carcinoma, poorly differentiated carcinoma with squamous features).
• Participant must have CSCC that is not amenable to surgery or radiation therapy, or recurrent despite prior surgery or radiation therapy, including locally advanced unresectable CSCC for which local therapy (surgery and/or radiation therapy) is not recommended. This includes CSCC occurring in patients who are not surgical candidates due to comorbidities and patients who refuse surgery (due to concerns about morbidity, disfigurement, etc).
• Participants must have measurable disease as per PET Response Criteria in Solid Tumors version
• (PERCIST 1.0),46 defined as any tumor (of any size) whose SUV lean (SUL) peak is greater than 1.5 times the mean SUL in the liver + 2 times its standard deviation. Mean SUL in the liver is measured in a 3-cm diameter spherical volume of interest (VOI), which is a measurement of the SUV background.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of cosibelimab in participants <18 years of age, children are excluded from this study.
• ECOG performance status 0-2 (see Appendix A for definitions of this and Karnofsky Performance Status).

• Participants must meet the following organ and marrow function as defined below:

  • Absolute neutrophil count ≥1.0 K/mcL
  • Platelets ≥30 K/mcL
  • Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL
  • AST(SGOT) ≤ 2.5 × institutional ULN
  • ALT(SGPT) ≤ 2.5 × institutional ULN
  • Adequate renal function, defined as defined as estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
  • Serum creatinine ≤ 3.0 x institutional ULN or ≤ 3.0 x baseline (grade ≤ 2 per CTCAE)
• Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
• PD-1 and PD-L1 immune checkpoint antibodies are classified as pregnancy class D. For this reason, and because other therapeutic agents used in this trial are potentially teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 120 days after completion of cosibelimab administration. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 120 days after completion of cosibelimab administration.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior treatment within the past 12 months with any of the following classes of drugs: anti-PD-1 inhibitors, anti-PD-L1 inhibitors, or anti-CTLA-4 inhibitors.
• Prior treatment within the past 6 months with CAR-T cell therapies, other cellular therapies, or multiagent cytotoxic chemotherapy regimens (e.g. R-CHOP). (Bispecific antibodies and EGFR- targeted therapies are permitted without a washout period.)
• Participants who have adverse events due to prior anti-cancer therapy not recovered to Grade 1 or less, with the exception of alopecia, sensory neuropathy, and cytopenias.
• Active autoimmune disease that is currently requiring systemic steroid treatment with prednisone >10mg daily (or equivalent), anti-CD20 antibodies, intravenous immunoglobulin (IVIG) or JAK inhibitors (ruxolitinib, tofacitinib, upadacitinib, etc).
• Severe interstitial lung disease (ILD), or a history of pneumonitis that has required oral or IV steroids in the past 5 years.
• Participants who are receiving any other investigational agents for cancer within 2 weeks of study enrollment.
• Participants who have uncontrolled, symptomatic infections, or infections requiring systemic antibiotics (prophylactic antimicrobials are permitted).
• Participants who have uncontrolled or unstable brain metastases (or other CNS metastases) for whom systemic steroids are required. These patients are excluded because steroids may interfere with the effectiveness of immune checkpoint therapy.
• Uncontrolled or significant cardiovascular disease.
• Current need for dialysis (hemodialysis or peritoneal dialysis).
• History of stem cell transplant or bone marrow transplant
• Psychiatric illness or social situation that would preclude study compliance.
• Pregnant and breastfeeding women are excluded from this study because cosibelimab is classified as pregnancy class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cosibelimab, breastfeeding should be discontinued if the mother is treated with cosibelimab.
• Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the study drug are excluded.

• COHORT A ONLY:

  • History of organ transplant other than kidney, including a heart, lung, or liver transplant, etc, with the exception of cornea transplantation. Cornea transplant is allowed if participant is not taking systemic immunosuppressive medication expressly for the purpose of corneal allograft.
  • History of severe allergic reaction attributed to sirolimus or everolimus, or other absolute contraindication to mTOR inhibitor, as determined by the treating physician.
• COHORT B ONLY: History of any solid organ transplant, with the exception of cornea transplantation. Cornea transplant is allowed if participant is not taking systemic immunosuppressive medication expressly for the purpose of corneal allograft.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Cosibelimab + Standard of Care Immunosuppressive Regimen; 40 Kidney transplant recipients with advanced CSCC will be enrolled and will complete the following-; Baseline visit; Cycle 1 through Cycle 17 (21-day cycle)Day 1: Predetermined dose Cosibelimab 1x daily.Day 1 through 21: pre-determined dose of Prednisone 1X dailyDay 1 through 21: determined dose of sirolimus or everolimus 1X daily; Follow-up every three months; Long-term follow-up	Drug: Cosibelimab; Anti-PD-L1 antibody, single dose vials, via intravenous (into the vein) infusion per protocol; Other Names: CK-301; Cosibelimab-ipdl; UNLOXCYT; Drug: Prednisone; Corticosteroid, per standard of care; Drug: Sirolimus; mTOR Inhibitor, per standard of care; Drug: Everolimus; mTOR Inhibitor, per standard of care
Experimental: Cohort B: Cosibelimab; 40 Participants with co-diagnosis of hematologic malignancy/myeloproliferative disorder and advanced CSCC will be enrolled and will complete-; Baseline visit; Cycle 1 through Cycle 17 (21-day cycle)--Day 1: Predetermined dose Cosibelimab 1x daily.; Follow-up every three months; Long-term follow-up	Drug: Cosibelimab; Anti-PD-L1 antibody, single dose vials, via intravenous (into the vein) infusion per protocol; Other Names: CK-301; Cosibelimab-ipdl; UNLOXCYT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response Rate (BORR)	BORR is defined as the proportion of participants whose best overall responses are complete metabolic response (CMR) and partial metabolic response (PMR). Per PERCIST 1.0 for target lesions, CMR is visual disappearance of all metabolically active tumor, and PMR is at least a 30% decrease in SUL peak (minimum 0.8-unit decrease) in the lesion with greatest uptake, not necessarily the same lesion.	Up to 102 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events (TEAEs) Rate	TEAEs rate is defined as the proportion of participants who experience one or more adverse events that emerge or worsen after the initiation of study treatment.	Treatment duration is up to 51 weeks, and adverse events will be collected through 30 days following the end of treatment.
Immune-related Adverse Events (AE) Rate	The immune-related AE rate is defined as the proportion of participants who experience at least one adverse event considered by the investigator to be immune-related during the study treatment period.	Treatment duration is up to 51 weeks, and adverse events will be collected through 30 days following the end of treatment.
Allograft Rejection and Allograft Loss Rate in Cohort A	Allograft rejection loss rate is defined as the proportion of participants in Cohort A who experience allograft rejection or allograft loss, as determined by elevated serum creatinine, urine protein levels, donor-derived cell-free DNA (dd-cfDNA), renal biopsy findings, or the need for renal replacement therapy.	Up to 51 weeks.
Median Progression-Free Survival (PFS)	PFS is defined as the time from registration to the earlier of progressive metabolic disease (PMD), as defined by PERCIST 1.1, or death from any cause. PFS will be estimated using the Kaplan-Meier method. Participants who are alive without documented disease progression at the time of analysis will be censored at the date of their last disease evaluation.	Tumor assessments will be performed before Cycle 3, 5 Day 1 (28-day cycles) and every 4 cycles through Cycle 17. Follow-up assessments will occur on Cycle 18, 21, 29, and 33 Day 1.
Duration of Response (DOR)	DOR, defined according to PERCIST 1.1, is measured using the Kaplan-Meier method from the first documentation of complete metabolic response (CMR) or partial metabolic response (PMR), whichever occurs first, to the earliest date of objectively documented recurrent or progressive metabolic disease (PMD), using the lowest recorded measurements since treatment initiation as the reference, or death from any cause. Participants without documented events will be censored at the date of their last disease evaluation.	2 years
Median Overall Survival (OS)	OS based on Kaplan-Meier method is defined as time from date of first dose until the date of death due to any cause. Participants are censored as date last known alive.	Up to 147 weeks
Median Disease Specific Survival (DSS)	DSS based on Kaplan-Meier method is defined as the time from study enrollment to death specifically due to advanced cutaneous squamous cell carcinoma (CSCC). Deaths from other causes are censored at the time of occurrence.	Up to 102 weeks.
Median Circulating Tumor DNA (ctDNA) Levels	ctDNA will be assessed from plasma using a personalized mPCR-NGS-based assay (Signatera™). ctDNA levels will be quantified as mean tumor molecules per milliliter of plasma (MTM/mL).	Up to 102 weeks.

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Checkpoint Therapeutics, Inc.
• Investigators: Principal Investigator: Ann Silk, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 15, 2030
• Study Completion (Estimated): December 15, 2032

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Lymphoma; Skin Cancer; Myeloma; Waldenstrom macroglobulinemia; Chronic lymphocytic leukemia (CLL); Cutaneous Squamous Cell Carcinoma; Kidney Transplant Recipient; Immunosuppressed; Advanced Cutaneous Squamous Cell Carcinoma; Solid Organ Transplant Recipient
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms, Plasma Cell; Skin Neoplasms; Waldenstrom Macroglobulinemia; Organic Chemicals; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Pregnadienediols; Everolimus; Sirolimus; Prednisone
• Other Study ID Numbers: 25-743

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No