A Study to Investigate the Novel Agent BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Advanced Melanoma That Has Not Responded to Other Forms of Treatment

NCT04526899 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: BNT111-012020-002195-122023-509513-36-00
• Study Type: interventional
• Target: 184
• Locations: 7 countries
• Sites: 49

Brief Summary

This is an open-label, randomized, multi-site, Phase II, interventional trial designed to evaluate the efficacy, tolerability, and safety of BNT111 + cemiplimab in anti-programmed death protein 1 (PD-1)/anti-programmed death ligand 1 (PD-L1)-refractory/relapsed patients with unresectable Stage III or IV melanoma. The contributions of BNT111 and cemiplimab will be delineated in single agent calibrator arms. Patients will be randomized in a 2:1:1 ratio to Arm 1 (BNT111 + cemiplimab) and calibrator Arm 2 (BNT111 monotherapy), and Arm 3 (cemiplimab monotherapy). Patients in single agent calibrator arms (Arms 2 and 3), who experience centrally verified disease progression under single agent treatment, may be offered addition of the other compound to the ongoing treatment after re-consent.

Conditions

Unresectable Melanoma; Melanoma Stage III; Melanoma Stage IV

Keywords

Cancer vaccine; Melanoma; Checkpoint inhibitor; Libtayo®; BNT111; Cemiplimab; RNA vaccine

Outcome Measures

Primary Outcomes (1)

• Arm 1: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants in whom a complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) was observed as best overall response by blinded independent central review (BICR). Per RECIST 1.1 criteria, CR defined as the disappearance of all target lesions and PR was defined as the \>=30% decrease in the sum of the longest diameter of target lesions.

  Up to 24 months

Secondary Outcomes (44)

• Arms 2 & 3: Objective Response Rate (ORR)

  Up to 24 Months

• Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR)

  Up to 24 Months

• Disease Control Rate (DCR) As Assessed by BICR

  Up to 24 months

• Time to Response (TTR) As Assessed by BICR

  Up to 24 months

• Progression-Free Survival (PFS) As Assessed by BICR

  Up to 24 Months

Study Arms (3)

BNT111 + cemiplimab

EXPERIMENTAL

Biological: BNT111; Biological: Cemiplimab

BNT111 monotherapy

EXPERIMENTAL

Biological: BNT111

Cemiplimab monotherapy

EXPERIMENTAL

Biological: Cemiplimab

Interventions

BNT111 BIOLOGICAL

IV injection

BNT111 + cemiplimab; BNT111 monotherapy

Cemiplimab BIOLOGICAL

IV infusion

BNT111 + cemiplimab; Cemiplimab monotherapy

Eligibility Criteria

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

You may qualify if:

• Patients must sign the written informed consent form (ICF) before any screening procedure.
• Patients must be aged \>=18 years on the date of signing the informed consent.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the trial.
• Patients must have histologically confirmed unresectable Stage III or IV (metastatic) cutaneous melanoma and measurable disease by RECIST v1.1.
• Patients must have confirmed disease progression on/after an approved anti-PD-1/PD-L1 regimen for melanoma as defined by RECIST v1.1.
• Previous exposure to approved anti-PD-1/PD-L1 containing regimen for at least 12 consecutive weeks and
• Current radiological progression to be confirmed by two scans 4 to 12 weeks apart. If progression is accompanied by new symptoms, or deterioration of performance status not attributed to toxicity, one scan is sufficient and
• Patients should have received at least one but no more than five lines of prior therapy for advanced disease.
• Patients must be able to tolerate additional anti-PD-1/PD-L1 therapy (i.e., did not permanently discontinue anti-PD-1/PD-L1 therapy due to toxicity).
• Patients must have known B-Raf proto-oncogene (BRAF) mutation status.
• Patients with BRAF V600-positive tumor(s) should have received prior treatment with a BRAF inhibitor (alone or in combination with a mitogen-activated protein kinase kinase \[MEK\] inhibitor).
• Note: Considering the possible negative impact of a prior BRAF/MEK therapy on immune system targeting therapies, patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms or evidence of rapid PD may be eligible for participation. This should be based on investigator assessment AND provided they are ineligible for, intolerant to, or have refused BRAF V600 mutation targeted therapy after receiving the information on possible other therapies including BRAF/MEK inhibitor-based therapy during the informed consent process.
• Patients must have an Eastern Cooperative Oncology Group performance status (PS) \<=1.
• Adequate bone marrow function, as defined by hematological parameters (as defined in the protocol).
• Patients must have serum lactate dehydrogenase \<= upper limit of normal.

You may not qualify if:

• Patients must not be pregnant or breastfeeding.
• Patients must not have history of uveal, acral, or mucosal melanoma.
• Patients must have no ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may pose a risk for irAEs.
• Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
• Patients must have no known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T cell-negative severe combined immunodeficiency \[SCID\]) or combined T and B cell immunodeficiencies (e.g., T and -B negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency).
• Patients with uncontrolled type 1 diabetes mellitus or with uncontrolled adrenal insufficiency are not eligible.
• Patients must have no uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. Mild cancer-related immunodeficiency (such as immunodeficiency treated with gamma globulin and without chronic or recurrent infection) is allowed.
• Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable anti-viral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
• Patients with known hepatitis B virus (HBV) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of trial treatment.
• Patients who are known hepatitis C virus (HCV) antibody positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
• Patients with HIV or hepatitis must have their disease reviewed by the specialist (e.g., infectious disease specialist or hepatologist) managing this disease prior to commencing and throughout the duration of their participation in the trial.
• Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis, progression or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, non-invasive, superficial bladder cancer or breast ductal carcinoma in situ).
• Current use or use within 3 months prior to trial enrollment of systemic immune suppression including:
• use of chronic systemic steroid medication (up to 5 mg/day prednisolone equivalent is allowed); patients using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible,
• other clinically relevant systemic immune suppression.

Sponsors & Collaborators

• BioNTech SE: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (49)

University Of Arizona College Of Medicine

Tucson, Arizona, 85724, United States

Location

University of California, San Francisco: Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158-3214, United States

Location

Sylvester Comprehensive Cancer Center/ UMHC

Miami, Florida, 33136, United States

Location

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68310, United States

Location

Atlantic Health System / Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Inova Dwight and Martha Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Border Medical Oncology

East Albury, 2640, Australia

Location

Gold Coast Hospital

Southport, 4215, Australia

Location

Melanoma Institute Australia

Sydney, 2060, Australia

Location

Klinik für Dermatologie, Dermatochirurgie, Allergologie, Klinikum Bremen-Ost, Gesundheitnord GmbH

Bremen, 28325, Germany

Location

Universitätsklinikum Essen (AoR)

Essen, 45147, Germany

Location

Universitätsklinikum Freiburg, Klinik füer Dermatologie und Venerologie

Freiburg im Breisgau, 79104, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel Hautkrebszentrum Kiel

Kiel, 24105, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin der Johannes Gutenberg Universität Mainz KoeR

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim GmbH

Mannheim, 68167, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Klinikum der Julius-Maximilians-Universität Würzburg

Würzburg, 97080, Germany

Location

Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Tumori Giovanni Paolo Ii

Bari, 70124, Italy

Location

Azienda ospedaliera universitaria Bologna

Bologna, 40138, Italy

Location

Fondazione del Piemonte per l'Oncologia, Istituto di Candiolo (IRCCs)

Candiolo, 10060, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumpori (IRST)

Meldola, 47014, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale - IRCCS · S.C. Oncologia Medica Melanoma, Immunoterapia Oncologica e Terapie Innovative

Naples, 80131, Italy

Location

IOV - Istituto Oncologico Veneto - IRCCS

Padua, 35128, Italy

Location

Policlinico Universitario Campus Bio-Medico

Rome, 00128, Italy

Location

Universita di Siena -Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte

Siena, 53100, Italy

Location

AOU Citta della Salute e della Scienza di Torino

Turin, 10126, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80214, Poland

Location

Szpital Specjalistyczny im. Luwika Rydygiera w Krakowie Sp. z o.o.

Krakow, 31-826, Poland

Location

Zachodniopomorskie Centrum Onkologii

Szczecin, 71-730, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Hospital Teresa Herrera (CHUAC)

A Coruña, 15009, Spain

Location

Hospital Universitari Germans Trias i Pujol (HUGTP)

Badalona, 8916, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Institut Català d'Oncologia l'Hospitalet

Barcelona, 08907, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, 30120, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, Spain

Location

Hospital Universitario Marques De Valdecilla

Santander, 39008, Spain

Location

Complejo Hospitalario Universitario De Santiago De Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

Valencia, 46026, Spain

Location

Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board

Glasgow, G12 0YN, United Kingdom

Location

The Christie - The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

+49 6131 9084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 26, 2020
• Study Start: May 19, 2021
• Primary Completion: January 25, 2024
• Study Completion: November 24, 2025
• Last Updated: January 8, 2026
• Results First Posted: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11); AU (3); GB (3); US (6); IT (9); ES (13); PL (4)