Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CONTRAC-2)

A Phase 2 Study of Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CONTRAC-2)

This is a phase II, multicenter, open label, single arm, non-randomized trial using Simon's optimal two-stage design to evaluate the efficacy of cemiplimab in kidney transplant recipients with advanced cutaneous squamous cell carcinoma. The hypothesis being tested is that cemiplimab alongside standardized immune suppression will generate anti-tumor activity without triggering allograft rejection.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant; Kidney Transplant Recipient; Advanced Cutaneous Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma (CSCC)
• Intervention / Treatment: Drug: Cemiplimab; Drug: Prednisone; Drug: Sirolimus; Drug: Cetuximab (EGFR inhibitor)

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: George Ansstas, MD; Phone Number: 314-362-5672; Email: gansstas@wustl.edu
• Study Contact Backup: Name: Naoka Murakami, MD, PhD; Phone Number: 314-362-4137; Email: naoka@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Sub-Investigator: Ningying Wu, PhD
      • Contact: George Ansstas, MD; Phone Number: 314-362-5672; Email: gansstas@wustl.edu
      • Contact: Naoka Murakami, MD, PhD; Phone Number: 314-362-4137; Email: naoka@wustl.edu
      • Principal Investigator: George Ansstas, MD
      • Principal Investigator: Naoka Murakami, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed locoregionally advanced and unresectable or recurrent/metastatic cutaneous squamous cell carcinoma (CSCC). Definitions that encompass unresectable disease include any of the following, after discussion at the multidisciplinary meeting:

  • Anatomically unresectable disease to include carotid artery encasement; invasion into the skull base, cavernous sinus, sagittal sinus; pre-vertebral fascia/vertebral body/vertebral artery; disseminated distant metastatic disease
  • Functionally unresectable disease resulting in the loss of sight, oral competency/speech/swallowing, or limb
  • Biologically unresectable disease to include satellitosis, in-transit/dermal metastasis, or disease which has failed 2 or more prior surgeries (by an experienced CSCC surgeon) or failed curative intent radiation therapy
• Measurable disease per RECIST 1.1.

• Received a kidney transplant. Must have a functioning allograft, be at least 6 months from last allograft transplantation, and have had no evidence of biopsy-proven allograft rejection (Banff 1A or above, requiring treatment) at any time. In order to be considered a functioning allograft, the following criteria must be met:

  • Estimated glomerular filtration rate (GFR) ≥ 30 mL/min (using the CKD-EPI equation either by Cr or Cystatin C based measurement) (Inker LA et al, 2021)
  • Baseline proteinuria < 0.5 g/day (by spot urine protein-creatinine ratio or 24-hr urine collection, if available)
  • Not receiving antiproliferative immunosuppressive medications. If patients are on antiproliferative immunosuppressive medications, they must be discontinued for at least 7 days before initiation of C1D1 (i.e. at the screening visit and/or during the lead-in period)
• At least 18 years of age.
• ECOG performance status ≤ 2

• Adequate bone marrow and organ function as defined below:

  • Leukocytes ≥ 2.2 K/cumm
  • Absolute neutrophil count ≥ 1.0 K/cumm
  • Platelets ≥ 90 K/cumm
  • Total bilirubin within normal institutional limits (except in cases where Gilbert syndrome is known or suspected, where total bilirubin should be < 3 mg/dL)
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
• The effects of cemiplimab on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for 4 months after last dose of cemiplimab.
• Able to switch immunosuppression regimen to sirolimus and prednisone if not already receiving sirolimus and prednisone as SOC.
• Able to understand and willing to sign an IRB approved written informed consent document and willing and able to comply with clinic visits and study-related procedures. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Received chemotherapy or radiotherapy within 2 weeks prior to C1D1. Note: prior cetuximab exposure is permitted, but it must have been discontinued at least 2 weeks prior to the start of cemiplimab.
• Received prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CLTA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways (including chimeric antigen receptor [CAR] T-cell therapies).

Note: prior topical or intralesional immunotherapies (e.g., imiquimod, talimogene laherparepvec) are permitted.

• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
• Currently receiving any other investigational agents.
• Unable to swallow pills.
• Currently receiving any medications or substances that are strong inhibitors or inducers of CYP3A4.
• Receipt of a live vaccine within 28 days of C1D1.
• Receipt of COVID-19 vaccination within 7 days of C1D1 or for which the planned COVID-19 vaccinations would not be completed 7 days prior to C1D1.
• Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression and if they are at least 4 weeks out from treatment. They must also be asymptomatic and on stable doses of anti-epileptic drugs (AEDs) and oral corticosteroids at the time of enrollment
• A history of allergic reactions attributed to or known hypersensitivity to cemiplimab or any of its components or other agents used in the study.
• Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. Note: the following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded.
• Any condition that requires ongoing/continuous corticosteroid therapy (> 10 mg prednisone/day or anti-inflammatory equivalent) within 7 days prior to C1D1. Patients who require a brief course of steroids (up to 2 days in the week before C1D1) or physiologic replacement are not excluded.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring hospitalization or treatment with IV anti-infectives within 14 days prior to C1D1; NYHA heart failure classifications of Class II, III, or IV; myocardial infarction or acute coronary syndrome within 12 months prior to C1D1; unstable angina pectoris; cardiac arrhythmia; transient ischemic attack or stroke within 12 months prior to C1D1.
• Known non-infectious pneumonitis or any history of interstitial lung disease.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.

• Uncontrolled infection with HIV, hepatitis B or C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).

  • Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count > 350 either spontaneously or on a stable antiviral regiment are eligible. For these participants, monitoring will be performed as per local standards.
  • Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of cemiplimab.
  • Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: if serum HBV DNA is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.
  • Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are eligible.

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: Standard immunosuppression + Cemiplimab + Cetuximab (optional); Patients will receive standardized immunosuppression (sirolimus and prednisone) lead-in treatment for 7 to 14 days prior to starting treatment with cemiplimab. Cemiplimab is given IV on Day 1 of every 21-day cycle for a maximum of 24 months. Sirolimus is continued during cemiplimab, and dynamic prednisone is continued for the first 6 cycles. If patient progresses during treatment with cemiplimab, patients will be offered cetuximab as salvage therapy at the investigator's discretion and will be administered according to standard of care (SOC).

Drug: Cemiplimab; Cemiplimab is administered intravenously (IV) at a dose of 350mg over 30 minutes on Day 1 of each 21-day cycle.; Other Names: Libtayo; Drug: Prednisone; Prednisone is administered orally and taken about the same time each day. Prednisone will be pulsed for Cycles 1-6 and continued to be pulsed or dose reduced for Cycles 7+. For Cycles 1-6: 40 mg dose will be administered the day before each cycle (Day -1 or Day 21) and Days 1-3, 20mg dose Days 4-6, and 10mg dose Days 7-20. For Cycles 7+: Dose will be administered pulsed as Cycles 1-6 or 10mg daily; Other Names: Deltasone; Rayos; Sterapred; Drug: Sirolimus; Sirolimus will be taken orally once daily at dose prescribed to achieve a goal trough level of 4-6 ng/mL. It should be taken around the same time daily. Sirolimus will be administered daily throughout each cycle.; Other Names: Rapamune; Drug: Cetuximab (EGFR inhibitor); Cetuximab may be administered according to standard of care (SOC).; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR is defined as the proportion of patients with Complete Response (CR) or Partial Response (PR). ORR will be assessed according to RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	From start of cemiplimab treatment through completion of follow-up (total estimated time 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events as assessed by CTCAE v6.0		Start of lead-in treatment through 90 days after discontinuation of cemiplimab (total estimated time 27 months and 2 weeks)
Discontinuation of treatment due to treatment-related adverse events (AEs)	Defined as the proportion of patients who permanently discontinue any study treatment due to a treatment-related AE. AEs will be assessed by CTCAE v6.0.	Start of lead-in treatment through completion of treatment (total estimated time 24 months and 2 weeks)
Kidney allograft rejection rate	Kidney allograft rejection rate is defined as the proportion of kidney transplant recipients who experience an episode of acute or chronic kidney rejection after receiving the study treatment.	From start of cemiplimab treatment through completion of follow-up (total estimated time 36 months)
Allograft loss rate	Allograft loss rate is defined as the proportion of kidney transplant recipients whose transplanted kidney ceases to function after receiving the study treatment, assessed throughout the study.	Start of cemiplimab treatment through completion of follow-up (total estimated time 36 months)
Overall Survival (OS)	OS is defined as the duration from the initiation of study treatment to death from any cause. Patients who are alive at the time of analyses will be censored at the date last known alive.	Start of cemiplimab treatment to death, whichever comes first (estimated time frame 36 months)
Progression-free survival (PFS)	PFS is defined as the duration from the initiation of cemiplimab to disease progression or death for any reason, whichever occurs first. Patients without documentation progression or death at the time of analysis will be censored at the date of last adequate disease assessment. PFS will be assessed according to RECIST v1.1. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).	Start of cemiplimab treatment to time of progression or completion of follow-up, whichever occurs first (estimated total time 36 months)
Duration of response (DoR)	DoR is defined as the duration from response initiation (when either complete response (CR) or partial response (PR) is first determined) to disease progression or death for any reason, whichever occurs first. Patients who achieve a CR or PR and do not have documented disease progression or death at the time of analysis will be censored at the date of their last adequate disease assessment.	Time of CR or PR response to time of progression or death for any reason, whichever comes first (total estimated time 36 months)
Overall response rate (ORR2) at 9 weeks	ORR at 9 weeks (+/- 1 week) after initiation of cetuximab (ORR2) is defined as the proportion of patients achieving a complete response or partial response per RECIST v1.1 at the tumor assessment conducted approximately 9 weeks after the initiation of cetuximab. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Start of cetuximab treatment to 9 weeks after start of cetuximab treatment (total time 9 weeks)
Progression-free survival (PFS2) at 9 weeks	PFS at 9 weeks (+/- 1 week) after initiation of cetuximab (PFS2) is defined as the proportion of patients who are alive and without disease progression at approximately 9 weeks following the initiation of cetuximab. PFS will be assessed according to RECIST v1.1. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).	Start of cetuximab treatment to 9 weeks after start of cetuximab treatment (total time 9 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: George Ansstas, MD, Washington University School of Medicine; Principal Investigator: Naoka Murakami, MD, PhD, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: July 11, 2026
• First Submitted That Met QC Criteria: July 11, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 11, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Advanced cancer; Kidney transplant; Cutaneous squamous cell carcinoma
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Pregnadienediols; Cetuximab; Sirolimus; Prednisone; cemiplimab
• Other Study ID Numbers: 26-x257

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: No