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

  • End date
    Jun 15, 2025
  • participants needed
  • sponsor
    BioNTech SE
Updated on 7 October 2022


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-PD-1-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.

Condition Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
Treatment Cemiplimab, BNT111
Clinical Study IdentifierNCT04526899
SponsorBioNTech SE
Last Modified on7 October 2022


Yes No Not Sure

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 an approved anti-PD-1 regimen for melanoma as defined by RECIST 1.1
Previous exposure to approved anti-PD-1 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
Inclusion into this trial must be within 6 months of confirmation of disease progression on anti-PD-1 treatment, regardless of any intervening therapy
Patients should have received pembrolizumab or nivolumab (with/without ipilimumab)
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 therapy (i.e., did not permanently discontinue anti-PD-1 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: 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 (ECOG) performance status (PS) ≤ 1
Adequate bone marrow function, as defined in the protocol
Patients must have serum lactate dehydrogenase (LDH) ≤ upper limit of normal (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 chronic kidney disease epidemiology collaboration (CKD-EPI) 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 C1D1, 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 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
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
chorionic gonadotropin [beta-hCG]) at screening. Patients that are
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
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

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 pose a risk for immune-related adverse events (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, 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 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
Prior/concomitant therapy
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
Current use or use within 3 months prior to trial enrollment of systemic immune suppression including
other clinically relevant systemic immune suppression
Other comorbidities
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
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
Current evidence of ongoing National Cancer Institute Common Terminology Criteria for Adverse Events (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 clinical significant per investigator's discretion, and those Grade 2 toxicities listed as permitted in other eligibility criteria
metastasis, progression or death (such as adequately treated carcinoma in situ
Patients who have had a splenectomy
of the cervix, basal or squamous cell skin cancer, localized prostate cancer
non-invasive, superficial bladder cancer or breast ductal carcinoma in situ)
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
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
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 CT or MRI scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart)
do not require steroid therapy within 14 days before the first dose of trial treatment
Treatment with other anti-cancer therapy including chemotherapy, radiotherapy
spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated
investigational, or biological cancer therapy within 3 weeks prior to the
first dose of trial treatment (6 weeks for nitrosureas). Adjuvant
angina pectoris requiring anti-anginal medication, uncontrolled cardiac arrhythmia(s), severe conduction abnormality, or clinically significant valvular disease
hormonotherapy used for breast cancer in long term remission is allowed
QTc (F) prolongation > 480 ms
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
History or current evidence of significant cardiovascular disease including, but not
limited to
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
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