Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab (NeoMatryx)

Neoadjuvant Merkel Cell Carcinoma Therapy (Tx) With the PD-1 Inhibitor Cemiplimab - A Randomized, Double-blind, Placebo-controlled, Non-comparative Phase II Study

The study is a randomized, double blind, placebo-controlled, non-comparative phase II trial that investigates the efficacy of neoadjuvant anti-PD-1 antibody Cemiplimab treatment in patients with clinical stage I or II Merkel cell carcinoma who have have undergone primary tumour excision and are pending sentinel lymph node biopsy.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Immunotherapy; Merkel Cell Carcinoma, Stage I; Merkel Cell Carcinoma, Stage II
• Intervention / Treatment: Drug: Cemiplimab 350 mg i.v. on day 1 of every 21 days cycle for 2 cycles; Drug: Placebo NaCl 0.9% solution i.v. on day 1 of every 21 days cycle for 2 cycles.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michelle Tez; Email: tez.michelle@ikf-khnw.de
• Study Contact Backup: Name: Ralf Gutzmer, Prof. Dr. med.; Email: Ralf.Gutzmer@Muehlenkreiskliniken.de

Study Locations

• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Nationales Centrum für Tumorerkrankungen
      • Contact: Jessica Hassel, Prof. Dr.
    • Mannheim, Baden-Wurttemberg, Germany, 68161
      • Universitätsklinikum Mannheim
      • Contact: Jochen Utikal, Prof. Dr.
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitatsklinikum Tubingen
      • Contact: Ulrike Leiter-Stöppke, Prof. Dr.
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Universitätsklinikum Regensburg
      • Contact: Sebastian Haferkamp, Prof. Dr.
    • Würzburg, Bavaria, Germany, 97080
      • Universitatsklinikum Wurzburg
      • Contact: Anja Gieserich, Dr.
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20246
      • Universitatsklinikum Hamburg-Eppendorf
      • Contact: Christoffer Gebhardt, Prof. Dr.
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Universitätsklinikum Frankfurt
      • Contact: Bastian Schilling, Prof. Dr.
  • North Rhine-Westphalia
    • Bielefeld, North Rhine-Westphalia, Germany, 33647
      • Klinikum Bielefeld
      • Contact: Selma Ugurel, Prof. Dr.
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitatsklinikum Koln
      • Contact: Cindy Franklin, Prof. Dr.
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitätsklinikum Essen
      • Contact: Dirk Schadendorf, Prof. Dr.
    • Minden, North Rhine-Westphalia, Germany, 32429
      • Johannes Wesling Klinikum Minden
      • Contact: Ralf Gutzmer, Prof. Dr.
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Mainz
      • Contact: Stefan Grabbe, Prof. Dr.
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig
      • Contact: Jan Christoph Simon, Prof. Dr.
  • Thuringia
    • Erfurt, Thuringia, Germany, 99089
      • HELIOS Klinikum Erfurt
      • Contact: Rudolph Herbst, Prof. Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. Patient has signed informed written consent.
2. Patients is 18 years and older at time of signing of written informed consent
3. Patient has diagnosis of Merkel cell carcinoma in clinical stage II, or in stage I with minimum diameter of 1 cm, with primary tumor already removed and a planned sentinel lymph nodes biopsy still pending.
4. Patient has ECOG performance status 0-2.

5. Patients has adequate laboratory parameters particularly for the blood count, renal and liver function parameters.

   1. Absolute number of neutrophils ≥ 1.5 x 109/L
   2. Platelets ≥ 75 x 109/L
   3. Hemoglobin ≥ 9 g/dL
   4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with Gilbert´s Disease and total bilirubin up to 3x ULN may be eligible after approval from trial's medical expert)
   5. AST (SGOT) and ALT (SGPT) ≤ 3x ULN
   6. AP ≤ 2.5x ULN
   7. Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL/min
6. Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of Cemiplimab. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
7. Patient must be willing to allow translational work-up of tissue samples (PT, sentinel lymph node biopsy).

Exclusion criteria

1. Patient has prior sentinel lymph node removal for the current MCC.
2. Patients received prior treatment with immunotherapy (such as PD-1/PD-L1 or CTL4) or any other systemic anti-tumor (MCC) therapy (incl. investigational therapies)
3. Patient has active or a history of hematological neoplasms including chronic lymphocytic leukemia (CLL), irrespective if these require treatment or not.
4. Patient had prior organ transplantation including allogenic stem-cell transplantation.

5. Patient receives immunosuppressive concomitant medication, EXCEPT for the following:

   i. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection).

   ii. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent.

   iii. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

6. Patient has known hypersensitivity to any component of the Cemiplimab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
7. Patient has active autoimmune or inflammatory disorders.
8. Patient has history of interstitial lung disease.
9. Patient has active infection requiring systemic therapy.

10. Patient has Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCV infection or diagnosis of immunodeficiency.

    NOTE: Patients are eligible if:

    • Patients have controlled HIV infection with CD4 counts is > 350 cells/μL and viral load is undetectable [HIV RNA PCR]. Patients with controlled HIV infection must be monitored per local standards during the trial.
    • Patients positive for HBV surface antigen have controlled HBV infection receiving anti-viral therapy and with undetectable serum viral load [HBV DNA PCR]. Patients with controlled infection must undergo periodic monitoring of HBV DNA and p must remain on anti-viral therapy for at least 6 months after last dose of Cemiplimab.
    • Patients positive for HCV antibody have controlled HCV infection with undetectable viral load [HCV RNA PCR].
11. Patent received vaccination with any live vaccine (e.g., intranasal flu vaccine) within 4 weeks before the first dose of Cemiplimab or planned vaccination with live vaccine during the trial
12. Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum β-HCG pregnancy test result within 7 days prior to initiation of study treatment.
13. Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.
14. Patient has known substance abuse or other psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
15. Patient is legally incapacitated or has limited legal capacity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Cemiplimab); 2 cycles of Cemiplimab (350 mg, i.v., Q3W) followed by sentinel lymph node biopsy	Drug: Cemiplimab 350 mg i.v. on day 1 of every 21 days cycle for 2 cycles; Patients will receive Cemiplimab 350 mg i.v. on day 1 of every 21 days cycle for 2 cycles; Other Names: LIBTAYO
Placebo Comparator: Arm B (placebo); 2 cycles of placebo followed by sentinel lymph node biopsy	Drug: Placebo NaCl 0.9% solution i.v. on day 1 of every 21 days cycle for 2 cycles.; Patients will receive NaCl 0.9% solution i.v. on day 1 of every 21 days cycle for 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nodal micrometastases-free rate	rate of patients without nodal micrometastases after 2 cycles of treatment, determined by sentinel lymph node biopsy	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	time from randomization until date of the first of the following events: MCC progression, MCC recurrence, and MCC-related death	up to 66 months
Overall survival	time from randomization until date of death from any cause	up to 66 months
Disease specific survival	time from randomization until date of MCC-related death	up to 66 months
Quality of life using FCRI-SF questionnaire	Quality of life determined using the FCRI-SF questionnaire	up to 66 months
Safety (AEs and SAEs)	incidence, nature, causality, frequency, timing and severity of adverse events using NCI CTCAE 5	up to 66 months
Quality of life using the mFACT-M questionnaire	Quality of life determined using the mFACT-M questionnaire	up to 66 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigation of prognostic and predictive biomarkers to estimate the risk of lymph node metastases and signs of immune activation in the sentinel lymph nodes	Biosamples will be used to determine the correlation of identified biomarkers with clinical outcome, i.e., nodal metastases-free rate, RFS, OS	up to 66 months

Collaborators and Investigators

• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Collaborators: Regeneron Pharmaceuticals; Prof. Gutzmer, Skin Cancer Center Minden, Johannes-Wesling-Klinikum Minden, Germany; Prof. Becker, Translational Skin Cancer Research University Duisburg-Essen, Germany
• Investigators: Study Director: Salah Al-Batran, Prof. Dr., Institut für Klinische Krebsforschung IKF GmbH; Principal Investigator: Ralf Gutzmer, Prof. Dr. med., Johannes Wesling Klinikum Minden; Principal Investigator: Juergen C. Becker, Prof. Dr. Dr., Translational Skin Cancer Research University Duisburg-Essen, Germany

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): July 31, 2031

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: sentinel lymph node; PD-1 antibody; skin cancer; Cemiplimab; merkel cell carcinoma; MCC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Infections; Virus Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; DNA Virus Infections; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Tumor Virus Infections; Polyomavirus Infections; Carcinoma, Neuroendocrine; Skin and Connective Tissue Diseases; Skin Neoplasms; Carcinoma, Merkel Cell; cemiplimab
• Other Study ID Numbers: NeoMatryx

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