Cemiplimab in AlloSCT/SOT Recipients With CSCC

NCT04339062 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 19-817
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study, Cemiplimab is being evaluated as a treatment for advanced cutaneous squamous cell carcinoma in participants who have previously received an allogeneic hematopoietic stem cell transplant or kidney transplant. \- This research study involves the following drug(s):

• Cemiplimab
• Everolimus or Sirolimus
• Prednisone

Conditions

Cutaneous Squamous Cell Carcinoma; Advanced Cancer

Keywords

Cutaneous Squamous Cell Carcinoma; Advanced Cancer; Allogeneic hematopoietic stem cell transplant; Kidney transplant

Outcome Measures

Primary Outcomes (1)

• Rate of Renal Transplant Rejection (Cohort 2) or GVHD (Cohort 1).

  The proportions of patients who have observed GVHD in Cohort 1 or renal transplant rejection in Cohort 2. Participants will be evaluable for from the time of their first treatment.

  First dose of study treatment up to 100 days

Secondary Outcomes (4)

• Progression-Free Survival

  Duration of follow-up (up to 36 months)

• Overall Survival

  Duration of follow-up (up to 36 months)

• Overall Response Rate

  Up to 1 year

• Duration of Response

  Duration of follow-up (up to 36 months)

Study Arms (2)

Cohort 1 Cemiplimab

EXPERIMENTAL

Participants who received allogeneic hematopoietic stem cell transplant \-- Cemiplimab: via IV, flat predetermined dosage every 21 days

Drug: Cemiplimab

Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

EXPERIMENTAL

Participants who received a kidney transplant will receive * Cemiplimab via IV, flat predetermined dosage every 21 days * Everolimus or Sirolimus-least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab * Prednisone 40 mg orally the day prior to the start of cemiplimab dosing (Cycle 1, Day 1) and then daily at tapering doses while receiving Cemiplimab

Drug: Cemiplimab; Drug: Everolimus; Drug: Sirolimus; Drug: Prednisone

Interventions

Cemiplimab DRUG

Cemiplimab: via IV, flat predetermined dosage every 21 days.

Also known as: Libtayo

Cohort 1 Cemiplimab; Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

Everolimus DRUG

Everolimus at least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab

Also known as: Afinitor, Zortress

Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

Sirolimus DRUG

Sirolimus at least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1) and then daily while receiving Cemiplimab

Also known as: Rapamune

Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

Prednisone DRUG

40 mg orally the day prior to the start of cemiplimab dosing (Cycle 1, Day 1) and then daily at tapered dosing while receiving Cemiplimab

Also known as: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

Cohort 2 Cemiplimab + Everolimus/Sirolimus + Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed, advanced or metastatic cutaneous squamous cell carcinoma (cSCC) with 1 or more measurable lesions (greater than or equal to 1 cm).
• A history of either (Cohort 1) allogeneic hematopoietic stem cell transplant (alloHSCT) and ≥ 2 years or 730 days from day 0 of their HSCT with adequate bone marrow function (see Section 3.1.6) and off of all systemic immunosuppression (topical agents permitted) for at least 3 months prior to enrollment; sequelae of chronic graft versus host disease (GVHD) is permitted (i.e. chronic dry eyes, sclerodermatous skin changes, etc.) if the patient is not on systemic immunosuppression, or (Cohort 2) a renal transplant with a functioning allograft (at least 6 months from allograft transplant) as determined by estimated glomerular filtration (GFR) rate (CKD-EPI equation \[40\], Appendix A) ≥30 mL/min, baseline proteinuria lower than 0.5 g/day (spot urine protein-creatinine ratio), and off antiproliferative immunosuppressive medications.
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix B).
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥ 2,200/mcL
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 90,000/mcL
• 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 × institutional upper limit of normal
• creatinine ≤ 1.5 × institutional upper limit of normal OR
• estimated GFR ≥ 30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (CKD-EPI equation).
• urine protein/creatinine ratio \< 0.5 (equal to less than 500 mg of proteinuria per day)
• Ability to understand and the willingness to sign a written informed consent document.
• A prior history of acute GVHD that has resolved, or sequelae of chronic GVHD following allo-HSCT is permitted. Active acute GVHD patients are excluded.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have unresolved toxicities from prior anti-cancer therapy more than 4 weeks earlier, defined as not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), grade 0 or 1.
• Participants who are receiving any other investigational agents.
• For Cohort 1 allo-HSCT patients enrolling to the study, corticosteroid doses \> 10 mg of prednisone daily or equivalent within 4 weeks of the first dose of PD-1 inhibitor are prohibited. For Cohort 2 renal transplant patients enrolling to the study, corticosteroid use is permitted if used as part of their immunosuppressive regimen for graft protection prior to enrollment.
• Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded.
• Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
• Kidney transplant recipients with active acute rejection.
• Allergy to cemiplimab or any of its components.
• Any prior exposure to the phosphoinositide 3-kinase inhibitor idelalisib.
• Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-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). Prior topical or intralesional immunotherapies (e.g. imiquimod, talimogene laherparepvec) are allowed.
• Subject with known and untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, baseline brain imaging is not required prior to enrollment in the study if patients are asymptomatic. Patients at least 4 weeks out from metastatic central nervous system (CNS) treatment are permitted to enroll, if they are asymptomatic, radiographically stable per the investigator, and on stable doses of anti-epileptic drugs (AEDs) and oral corticosteroids (for Cohort 1 only, the patient must be on 10 mg of prednisone daily equivalent dosing or less, see 3.2.2) at the time of enrollment.
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as \[http://medicine.iupui.edu/clinpharm/ddis/table.aspx\]. Medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Known non-infectious pneumonitis or any history of interstitial lung disease.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• Hanna GJ, Dharanesswaran H, Giobbie-Hurder A, Harran JJ, Liao Z, Pai L, Tchekmedyian V, Ruiz ES, Waldman AH, Schmults CD, Riella LV, Lizotte P, Paweletz CP, Chandraker AK, Murakami N, Silk AW. Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma. J Clin Oncol. 2024 Mar 20;42(9):1021-1030. doi: 10.1200/JCO.23.01498. Epub 2024 Jan 22.

  PMID: 38252908 DERIVED

• Bonilla M, Gudsoorkar P, Wanchoo R, Herrmann SM, Jhaveri KD. Onconephrology 2022: An Update. Kidney360. 2023 Feb 1;4(2):258-271. doi: 10.34067/KID.0001582022. Epub 2022 Dec 9.

  PMID: 36821617 DERIVED

• Paoluzzi L, Ow TJ. Safe Administration of Cemiplimab to a Kidney Transplant Patient with Locally Advanced Squamous Cell Carcinoma of the Scalp. Curr Oncol. 2021 Jan 19;28(1):574-580. doi: 10.3390/curroncol28010057.

  PMID: 33477979 DERIVED

MeSH Terms

Interventions

cemiplimab; Everolimus; Sirolimus; Prednisone

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Limited sample size.

Results Point of Contact

• Title: Dr. Glenn Hanna
• Organization: Dana-Farber Cancer Institute

glenn_hanna@dfci.harvard.edu

617-632-3090

Study Officials

• Glenn J Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 8, 2020
• Study Start: November 3, 2020
• Primary Completion: June 12, 2023
• Study Completion: March 1, 2025
• Last Updated: April 23, 2025
• Results First Posted: June 12, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)