Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD1-refractory/Relapsed, Unresectable Stage III or IV Melanoma

Study Purpose

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-PD1-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 in single agent calibrator arms, who experience disease progression under single agent treatment, may be offered addition of the other compound to the ongoing treatment after re-consent.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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 1.1.
  • - Patients must have confirmed disease progression on/after approved anti-PD1 regimen for melanoma as defined by RECIST 1.1 and further defined according to the Society for ImmunoTherapy of Cancer (SITC) Immunotherapy Resistance Taskforce: 1.
Previous exposure to approved anti-PD1 containing regimen for at least 12 consecutive weeks and 2. Radiological progression to be confirmed by 2 scans 4-12 weeks apart. If progression is accompanied by new symptoms, or deterioration of performance status not attributed to toxicity, one scan is sufficient. 3. Progression must be while on treatment with approved anti-PD1 regimen for melanoma or within 6 months of discontinuing anti-PD1 treatment, and regardless of any intervening therapy.
  • - Patients should have received pembrolizumab or nivolumab (with/without ipilimumab).
  • - Patients should have received at least 1 but no more than 5 lines of prior therapy for advanced disease.
  • - Patients must be able to tolerate additional anti-PD1 therapy (i.e., did not permanently discontinue anti-PD1 therapy due to toxicity).
  • - Patients must have known 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 MEK inhibitor) in addition to treatment with pembrolizumab or nivolumab with or without ipilimumab Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms or evidence of rapidly progressive disease are not required to be treated with a BRAF inhibitor (alone or in combination with a MEK inhibitor) based on investigator's decision.
  • - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
  • - Adequate bone marrow function as defined in the protocol.
  • - Patients must have serum lactate dehydrogenase (LDH) ≤ ULN.
  • - Patient should have adequate hepatic function, as defined in the protocol.
  • - Patient should have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) ≥30 mL/min using the CKD-EPI equation.
  • - Patient should be stable with adequate coagulation, as defined in the protocol.
  • - Patients must provide the following biopsy samples: 1.
All patients: must provide a tumor tissue sample (formalin-fixed paraffin-embedded [FFPE] blocks/slides) from fresh biopsy collected before Cycle 1 Day 1, preferably derived from advanced disease stage, or archival tissue (not older than 3 years). 2. Patients at selected trial sites: must be amenable to a pre-treatment and on-treatment biopsy and must provide a mandatory biopsy which contains tumor tissue and is taken after failure/stop of last prior treatment and an on-treatment biopsy.
  • - 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.
For a definition of adequate contraception.

Exclusion Criteria:

  • - 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 suggest risk for immune-related adverse events (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.
  • - Patients must have no uncontrolled infection with human immunodeficiency virus, 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. 1. Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. 2. Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA 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. 3. Patients who are known hepatitis C virus antibody positive (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 permitted. 4. 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. Prior/concomitant therapy:
  • - Systemic immune suppression: 1.
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, 2. 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. Other comorbidities:
  • - Current evidence of Common Terminology Criteria for Adverse Events (CTCAE version 5.0) Grade >1 toxicity before the start of treatment, except for hair loss, hearing loss, or laboratory abnormalities not considered clinical significant per investigator's discretion, and those Grade 2 toxicities listed as permitted in other eligibility criteria.
Patients with Grade 2 neuropathy may be eligible at investigator's discretion.
  • - 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, or 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: 1. had radiotherapy or another appropriate therapy for the brain or spinal bone metastases, 2. have no neurological symptoms that can be attributed to the current brain lesions, 3. have stable brain or spinal disease on the CT or MRI scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart), 4. do not require steroid therapy within 14 days before the first dose of trial treatment, 5. 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: 1.
angina pectoris requiring anti-anginal medication, uncontrolled cardiac arrhythmia(s), severe conduction abnormality, or clinically significant valvular disease, 2. QTc (F) prolongation >480 ms, 3. arterial thrombosis or pulmonary embolism within ≤6 months before the start of treatment, 4. myocardial infarction within ≤6 months before the start of treatment, 5. pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), non-malignant pleural effusion (CTCAE Grade ≥2) or malignant pleural effusion (CTCAE Grade ≥3) within ≤6 months before the start of treatment, 6. 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.
Other exclusions:
  • - 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.

Trial Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

BioNTech SE
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

BioNTech Responsible Person
Principal Investigator Affiliation BioNTech SE
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Not yet recruiting

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
Arms & Interventions


Experimental: BNT111 + cemiplimab

Experimental: BNT111 monotherapy

Experimental: Cemiplimab monotherapy


Biological: - BNT111

IV injection

Biological: - Cemiplimab

IV infusion

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

BioNTech clinical trials patient information

+49 6131 9084

For additional contact information, you can also visit the trial on

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