Melanoma Stage IIIPhase 2NCT04526899
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
A Phase 2 study testing BNT111 and Cemiplimab in people with Melanoma Stage III and Melanoma Stage IV, run by BioNTech SE at 49 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
- What is being tested?
- BNT111 and Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 49 sitesin 7 countries
- Study dates
- 19 May 2021to 24 Nov 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Inclusion into this trial must be within 6 months of confirmation of disease progression on anti-PD-1/PD-L1 treatment, regardless of any intervening therapy.
- 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.
- Patient should have adequate hepatic function, as defined in the protocol.
- Patient should have adequate kidney function, assessed by the estimated glomerular filtration rate >= 30 mL/min using the chronic kidney disease epidemiology collaboration equation.
- Patient should be stable with adequate coagulation, as defined in the protocol.
- Patients must provide the following biopsy samples:
- All patients: must provide a tumor tissue sample (formalin fixed paraffin-embedded [FFPE] blocks/slides) from a fresh biopsy collected before Visit Cycle1 Day1, or archival tissue. The archival tissue can be an FFPE block (not older than 3 years) or freshly cut slides (special storage conditions and immediate shipment to specialty lab are required), preferably derived from advanced disease stage.
- Patients at selected trial sites: After additional consent, patients must be amenable to pre-treatment and on-treatment peripheral blood mononuclear cell (PBMC) sampling and optional biopsy. If amenable, patients should provide a PBMC sample and optionally a biopsy which contains tumor tissue after failure/stop of last prior trial treatment.
- Women of childbearing potential (WOCBP) must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at screening. Patients that are postmenopausal or permanently sterilized can be considered as not having reproductive potential. Female patients of reproductive potential must agree to use highly effective contraception during and for 6 months after the last trial drug administration.
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial starting at screening, during the trial and for 6 months after receiving the last trial treatment.
- A man who is sexually active with a WOCBP and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the trial and for 6 months after receiving the last trial treatment.
- Patients must have confirmed disease progression on monotherapy in Arm 2 or 3 of the trial.
- An initial radiological progression needs to be verified by BICR.
- Radiological progression to be confirmed by two scans 4 to 12 weeks apart unless initial progression is accompanied by new symptoms, or deterioration of PS not attributed to toxicity, in which case one scan is sufficient.
- Patients must sign a new ICF to continue with add-on therapy. Informed consent must be documented before any add-on-specific procedure is performed.
- WOCBP must have a negative serum (beta-hCG) at baseline. Patients that are postmenopausal or permanently sterilized can be considered as not having reproductive potential.
- Female patients of reproductive potential must agree to use adequate contraception during and for 6 months after the last trial drug administration.
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial starting at screening, during the trial and for 6 months after receiving the last trial treatment.
- A man who is sexually active with a WOCBP and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the trial and for 6 months after receiving the last trial treatment.
Who cannot join
- 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.
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- 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.
- Treatment with other anti-cancer therapy including chemotherapy, radiotherapy, investigational, or biological cancer therapy within 3 weeks prior to the first dose of trial treatment (6 weeks for nitrosureas). Adjuvant hormonotherapy used for breast cancer in long term remission is allowed.
- Current evidence of ongoing National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) Grade > 1 toxicity of prior therapies before the start of treatment, with the exception of hair loss, hearing loss, Grade 2 peripheral neuropathy, or laboratory abnormalities not considered clinically significant per investigator's discretion, and those Grade 2 toxicities listed as permitted in other eligibility criteria.
- Patients who have a local infection (e.g., cellulitis, abscess) or systemic infection (e. g., pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of trial treatment.
- Patients who have had a splenectomy.
- Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, have not fully recovered from surgery, or have a surgery planned during the time of trial participation.
- Current evidence of new or growing brain or spinal metastases during screening. Patients with leptomeningeal disease are excluded. Patients with known brain or spinal metastases may be eligible if they:
- had radiotherapy or another appropriate therapy for the brain or spinal bone metastases,
- have no neurological symptoms that can be attributed to the current brain lesions,
- have stable brain or spinal disease on the computed tomography or magnetic resonance imaging scan within 4 weeks before randomization (confirmed by stable lesions on two scans at least 4 weeks apart, the second scan can be carried out during screening),
- do not require steroid therapy within 14 days before the first dose of trial treatment,
- spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated.
- History or current evidence of significant cardiovascular disease including, but not limited to:
- angina pectoris requiring anti-anginal medication, uncontrolled cardiac arrhythmia(s), severe conduction abnormality, or clinically significant valvular disease,
- QTc (F) prolongation > 480 ms,
- arterial thrombosis or pulmonary embolism within ≤ 6 months before the start of treatment,
- myocardial infarction within ≤ 6 months before the start of treatment,
- pericarditis (any NCI-CTCAE grade), pericardial effusion (NCI-CTCAE Grade >= 2), non-malignant pleural effusion (NCI-CTCAE Grade >=2) or malignant pleural effusion (NCI-CTCAE Grade >= 3) within <= 6 months before the start of treatment,
- Grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class >= II within <=6 months before the start of treatment.
- Patients who have received a live vaccine within 28 days of planned start of trial therapy.
- Known hypersensitivity to the active substances or to any of the excipients.
- Presence of a severe concurrent illness or other condition (e.g., psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol.
- Prior treatment with BNT111 and/or with cemiplimab.
- Prior toxicity related to trial medication should have resolved to NCI-CTCAE v5.0 Grade ≤ 1 before the start of add-on treatment and may not have led to permanent discontinuation.
- The time between confirmed PD on monotherapy and start of add-on therapy shall not exceed 6 weeks.
- Current evidence of new or growing brain or spinal metastases at baseline (lesions that remained stable during initial treatment are allowed).
- Systemic immune suppression:
- 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.
- Presence of cardiovascular, renal, hepatic or any other disease that in the investigator's opinion, may increase the risks associated with trial participation or require treatments that may interfere with the conduct of the trial or the interpretation of trial results.
Trial locations and contacts
49 sites in 7 countries.
49 sites in 7 countries
Spain13 sites
Hospital Teresa Herrera (CHUAC)
A Coruña, 15009
Hospital Universitari Germans Trias i Pujol (HUGTP)
Badalona, 8916
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital De La Santa Creu I Sant Pau
Barcelona, 08041
Institut Català d'Oncologia l'Hospitalet
Barcelona, 08907
Hospital Universitario Virgen de la Arrixaca
El Palmar, 30120
Hospital General Universitario Gregorio Maranon
Madrid, 28007
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Puerta de Hierro - Majadahonda
Madrid, 28222
Hospital Universitario Marques De Valdecilla
Santander, 39008
Complejo Hospitalario Universitario De Santiago De Compostela
Santiago de Compostela, 15706
Hospital Universitario Virgen del Rocio
Seville, 41013
Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
Valencia, 46026
Germany11 sites
Klinik für Dermatologie, Dermatochirurgie, Allergologie, Klinikum Bremen-Ost, Gesundheitnord GmbH
Bremen, 28325
Universitätsklinikum Essen (AoR)
Essen, 45147
Universitätsklinikum Freiburg, Klinik füer Dermatologie und Venerologie
Freiburg im Breisgau, 79104
Universitätsklinikum Heidelberg
Heidelberg, 69120
Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel Hautkrebszentrum Kiel
Kiel, 24105
Universitätsklinikum Leipzig
Leipzig, 04103
Universitätsmedizin der Johannes Gutenberg Universität Mainz KoeR
Mainz, 55131
Universitätsklinikum Mannheim GmbH
Mannheim, 68167
Klinikum Nürnberg Nord
Nuremberg, 90419
University Hospital Tübingen
Tübingen, 72076
Klinikum der Julius-Maximilians-Universität Würzburg
Würzburg, 97080
Italy9 sites
Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Tumori Giovanni Paolo Ii
Bari, 70124
Azienda ospedaliera universitaria Bologna
Bologna, 40138
Fondazione del Piemonte per l'Oncologia, Istituto di Candiolo (IRCCs)
Candiolo, 10060
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumpori (IRST)
Meldola, 47014
Istituto Nazionale Tumori Fondazione Pascale - IRCCS · S.C. Oncologia Medica Melanoma, Immunoterapia Oncologica e Terapie Innovative
Naples, 80131
IOV - Istituto Oncologico Veneto - IRCCS
Padova, 35128
Policlinico Universitario Campus Bio-Medico
Rome, 00128
Universita di Siena -Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
Siena, 53100
AOU Citta della Salute e della Scienza di Torino
Turin, 10126
United States6 sites
Inova Dwight and Martha Schar Cancer Institute
Fairfax, Virginia, 22031
Sylvester Comprehensive Cancer Center/ UMHC
Miami, Florida, 33136
Atlantic Health System / Morristown Medical Center
Morristown, New Jersey, 07962
Oncology Hematology West P.C. dba Nebraska Cancer Specialists
Omaha, Nebraska, 68310
University of California, San Francisco: Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158-3214
University Of Arizona College Of Medicine
Tucson, Arizona, 85724
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80214
Szpital Specjalistyczny im. Luwika Rydygiera w Krakowie Sp. z o.o.
Krakow, 31-826
Zachodniopomorskie Centrum Onkologii
Szczecin, 71-730
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw, 02-781
Australia3 sites
Border Medical Oncology
East Albury, 2640
Gold Coast Hospital
Southport, 4215
Melanoma Institute Australia
Sydney, 2060
United Kingdom3 sites
Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board
Glasgow, G12 0YN
The Christie - The Christie NHS Foundation Trust
Manchester, M20 4BX
Royal Cornwall Hospital
Truro, TR1 3LJ
About this study
Official title: Open-label, Randomized Phase II Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma
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
- Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
- Being tested
- BNT111, Cemiplimab
- Keywords
- Cancer vaccine, Melanoma, Checkpoint inhibitor, Libtayo®, BNT111, Cemiplimab, RNA vaccine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT111Biological
IV injection
CemiplimabBiological
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| BNT111 + cemiplimab | Experimental | Not described Receives: Biological: BNT111; Biological: Cemiplimab |
| BNT111 monotherapy | Experimental | Not described Receives: Biological: BNT111 |
| Cemiplimab monotherapy | Experimental | Not described Receives: Biological: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 months
Secondary outcomes (44)
Arms 2 & 3: Objective Response Rate (ORR)
ORR is defined as the percentage of participants in whom a CR or PR according to RECIST v1.1 observed as best overall response by BICR. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 Months
Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR)
DOR is defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (progressive disease, PD) by BICR or death from any cause (whichever occurs first). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 Months
Disease Control Rate (DCR) As Assessed by BICR
DCR is defined as the percentage of participants in whom a CR, PR or stable disease (SD; assessed at least 6 weeks after first dose) is observed as best overall response by BICR. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 months
Time to Response (TTR) As Assessed by BICR
TTR is defined as the time from randomization to the first objective tumor response (CR or PR) by BICR. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 months
Progression-Free Survival (PFS) As Assessed by BICR
PFS is defined as the time from randomization to first objective tumor progression (PD) by BICR or death from any cause (whichever occurs first). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 Months
Objective Response Rate (ORR) As Assessed by the Investigator
ORR is defined as the percentage of participants in whom a CR or PR according to RECIST v1.1 observed as best overall response by investigator. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 months
Duration of Response (DOR) As Assessed by the Investigator
DOR is defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (progressive disease, PD) by BICR or death from any cause (whichever occurs first). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 Months
Disease Control Rate (DCR) As Assessed by the Investigator
DCR defined as the percentage of participants in whom a CR, PR or stable disease (SD; assessed at least 6 weeks after first dose) is observed as best overall response by investigator. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 months
Time to Response (TTR) As Assessed by the Investigator
TTR is defined as the time from randomization to the first objective tumor response (CR or PR) as assessed by investigator. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 months
Progression-Free Survival (PFS) As Assessed by the Investigator
PFS is defined as the time from randomization to first objective tumor progression (PD) by investigator or death from any cause (whichever occurs first). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 24 Months
Arm 1: Overall Survival (OS)
OS is defined as the time from randomization to death from any cause. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 48 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
A treatment-emergent adverse event (TEAE) is defined as any AE with an onset date on or after the first administration of trial treatment (if the AE was absent before the first administration of trial treatment) or worsened after the first administration of trial treatment (if the AE was present before the first administration of trial treatment). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 27 months
Number of Participants With Immune-Related Adverse Events (irAE)
AEs related to the use of immune checkpoint inhibitor (ICI) therapy are defined as immune-related (IR) AEs (irAEs). Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 27 months
Number of Participants Reporting Dose Reduction and Discontinuation Due to TEAE
Participants with dose reduction and discontinuation due to TEAE will be reported. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 27 months
Change From Baseline in Laboratory Parameters Values: Hematology: Basophils
Blood samples will be collected for the assessment of hematology parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematology: Eosinophils
Blood samples will be collected for the assessment of hematology parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematocrit
Blood samples will be collected for the assessment of hematology parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hemoglobin
Blood samples will be collected for the assessment of hematology parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematology: Lymphocytes
Blood samples will be collected for the assessment of hematology parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Albumin
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alkaline Phosphatase
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alanine Aminotransferase
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Amylase
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Aspartate Aminotransferase
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Bilirubin
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatine Kinase
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatinine
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: C-Reactive Protein
Blood samples will be collected for the assessment of clinical chemistry parameters. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Activated Partial Thromboplastin Time
Blood samples will be collected for the assessment of coagulation factors. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Prothrombin Time
Blood samples will be collected for the assessment of coagulation factors. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Endocrine Tests: Thyroxine
Blood samples will be collected for the assessment of endocrine tests. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Urinalysis: pH
Urine samples will be collected for the assessment of pH. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Participants with clinically significant abnormalities in laboratory parameters will be reported. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 25 months
Change From Baseline in Vital Signs Parameters: Systolic Blood Pressure
Systolic blood pressure (in mmHg) will be assessed. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Diastolic Blood Pressure
Diastolic blood pressure (in mmHg) will be assessed. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Heart Rate
Heart rate (in beats per minute) will be assessed. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Respiratory Rate
Respiratory Rate (in breaths per minute) will be assessed. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Body Temperature
Body Temperature (in degree Celsius) will be assessed. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Participants with clinically significant abnormalities in vital sign parameters will be reported. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 25 months
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items (EORTC QLQ-C30) Global Health Status Total Score
Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items (EORTC QLQ-C30) Global Health Status Score will be reported. Each item, except Global Health Status, is answered on a four-point scale (1-4): 1-not at all, 2-a little, 3-quite a bit, 4-very much. Response to Global Health Status is measured on a 1 to 7 scale. "1" being very poor and "7" being excellent. Positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. Raw data was linearly transformed to be in a range from 0-100 where a higher score represents good health status, while lower scores indicate poor health status. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Change From Baseline in EORTC QLQ-C30 Functional Scales Score
The EORTC QLQ-C30 questionnaire incorporates nine multi-item scales: 5 functional scales (physical, cognitive, role, emotional, and social); 3 symptom scales (pain, fatigue, and appetite loss) and a Global Health Status/QoL scale. EORTC QLQ-C30 Physical Functioning Score is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening of symptoms. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Changes From Baseline in EORTC QLQ-C30 Symptoms Scales Score
The EORTC QLQ-C30 questionnaire incorporates nine multi-item scales: 5 functional scales (physical, cognitive, role, emotional, and social); 3 symptom scales (pain, fatigue, and appetite loss) and a Global Health Status/QoL scale. Each item, except Global Health Status, is answered on a four-point scale (1-4): 1-not at all, 2-a little, 3-quite a bit, 4-very much. Each scale (symptom scale [pain, fatigue, and appetite loss] and Global Health Status/Quality of Life [QoL] scale) was linearly transformed to be in range from 0-100 where a higher score represents good health status, while lower scores indicate poor health status. Data for this outcome measure will be reported at the time of final results posting.
Measured: From Baseline up to 25 months
Time to First Clinically Meaningful Deterioration in Global Health Status Score as Measured by EORTC QLQ-C30
Time to first clinically meaningful deterioration in global health status score as measured by EORTC QLQ-C30 will be reported. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 25 months
Time to First Clinically Meaningful Deterioration in Symptoms and Functioning as Measured by EORTC QLQ-C30
Time to first clinically meaningful deterioration in symptoms and functioning as measured by EORTC QLQ-C30 will be reported. Data for this outcome measure will be reported at the time of final results posting.
Measured: Up to 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2020
- Study start19 May 2021
- Primary completion25 Jan 2024
- Study completion24 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526899
- Sponsor's protocol ID
- BNT111-01
- Other IDs
- 2020-002195-12, 2023-509513-36-00, 2023
- Status last verified
- Dec 2025
- First submitted
- 18 Aug 2020
- Last updated
- 8 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Randomized Phase II Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma
- ClinicalTrials.gov ID
- NCT04526899
- Acronym / sponsor ID
- BNT111-01
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
- Keywords
- Cancer vaccine, Melanoma, Checkpoint inhibitor, Libtayo®, BNT111, Cemiplimab, RNA vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 19 May 2021 (actual)
- Primary completion
- 25 Jan 2024 (actual)
- Study completion
- 24 Nov 2025 (actual)
- First posted
- 26 Aug 2020 (actual)
- Results
- Posted 15 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BNT111 + cemiplimab | Experimental | Biological: BNT111, Biological: Cemiplimab |
| BNT111 monotherapy | Experimental | Biological: BNT111 |
| Cemiplimab monotherapy | Experimental | Biological: Cemiplimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 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.
Key exclusion criteria (44 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT111IV injection | Biological | BNT111 + cemiplimab, BNT111 monotherapy |
| CemiplimabIV infusion | Biological | BNT111 + cemiplimab, Cemiplimab monotherapy |
Primary outcome
Arm 1: Objective Response Rate (ORR)
Time frame: Up to 24 months
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.
44 secondary outcomes
Arms 2 & 3: Objective Response Rate (ORR)
Time frame: Up to 24 Months
Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR)
Time frame: Up to 24 Months
Disease Control Rate (DCR) As Assessed by BICR
Time frame: Up to 24 months
Time to Response (TTR) As Assessed by BICR
Time frame: Up to 24 months
Progression-Free Survival (PFS) As Assessed by BICR
Time frame: Up to 24 Months
Objective Response Rate (ORR) As Assessed by the Investigator
Time frame: Up to 24 months
Duration of Response (DOR) As Assessed by the Investigator
Time frame: Up to 24 Months
Disease Control Rate (DCR) As Assessed by the Investigator
Time frame: Up to 24 months
Time to Response (TTR) As Assessed by the Investigator
Time frame: Up to 24 months
Progression-Free Survival (PFS) As Assessed by the Investigator
Time frame: Up to 24 Months
Arm 1: Overall Survival (OS)
Time frame: Up to 48 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 27 months
Number of Participants With Immune-Related Adverse Events (irAE)
Time frame: Up to 27 months
Number of Participants Reporting Dose Reduction and Discontinuation Due to TEAE
Time frame: Up to 27 months
Change From Baseline in Laboratory Parameters Values: Hematology: Basophils
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematology: Eosinophils
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematocrit
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hemoglobin
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Hematology: Lymphocytes
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Albumin
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alkaline Phosphatase
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alanine Aminotransferase
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Amylase
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Aspartate Aminotransferase
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Bilirubin
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatine Kinase
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatinine
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: C-Reactive Protein
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Activated Partial Thromboplastin Time
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Prothrombin Time
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Endocrine Tests: Thyroxine
Time frame: From Baseline up to 25 months
Change From Baseline in Laboratory Parameters Values: Urinalysis: pH
Time frame: From Baseline up to 25 months
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Time frame: Up to 25 months
Change From Baseline in Vital Signs Parameters: Systolic Blood Pressure
Time frame: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Diastolic Blood Pressure
Time frame: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Heart Rate
Time frame: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Respiratory Rate
Time frame: From Baseline up to 25 months
Change From Baseline in Vital Signs Parameters: Body Temperature
Time frame: From Baseline up to 25 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Time frame: Up to 25 months
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items (EORTC QLQ-C30) Global Health Status Total Score
Time frame: From Baseline up to 25 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioNTech Responsible Person study director
BioNTech SE
49 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BNT111 and Cemiplimab in people with Melanoma Stage III and Melanoma Stage IV, run by BioNTech SE at 49 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in Spain, Germany, Italy, United States, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm 1: Objective Response Rate (ORR) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.