Melanoma Clinical Trial

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

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-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.

View Eligibility Criteria

Eligibility 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 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 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.

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.
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).

Prior/concomitant therapy:

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.

Other comorbidities:

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.
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 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,
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.

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.

Study is for people with:

Melanoma

Phase:

Phase 2

Estimated Enrollment:

180

Study ID:

NCT04526899

Recruitment Status:

Recruiting

Sponsor:

BioNTech SE

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There are 58 Locations for this study

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University Of Arizona College Of Medicine
Tucson Arizona, 85724, United States
University of California, San Francisco: Helen Diller Family Comprehensive Cancer Center
San Francisco California, 94158, United States
Saint John's Health Center - John Wayne Cancer Institute (JWCI)
Santa Monica California, 90404, United States
Sylvester Comprehensive Cancer Center/ UMHC
Miami Florida, 33136, United States
Lewis Hall Singletary Oncology Center at John D. Archbold Memorial Hospital
Thomasville Georgia, 31792, United States
Rush University Medical Center
Chicago Illinois, 60612, United States
Norton Cancer Institute
Louisville Kentucky, 40241, United States
Oncology Hematology West P.C. dba Nebraska Cancer Specialists
Grand Island Nebraska, 68893, United States
Oncology Hematology West P.C. dba Nebraska Cancer Specialists
Omaha Nebraska, 68310, United States
Atlantic Health System / Morristown Medical Center
Morristown New Jersey, 07962, United States
Icahn School of Medicine at Mount Sinai, Mount Sinai Medical Center
New York New York, 10029, United States
Guthrie Medical Group, PC
Sayre Pennsylvania, 18840, United States
Tennessee Oncology Nashville / Sarah Cannon
Nashville Tennessee, 37203, United States
Inova Dwight and Martha Schar Cancer Institute
Fairfax Virginia, 22031, United States
Border Medical Oncology
East Albury , 2640, Australia
Gold Coast Hospital
Southport , 4215, Australia
Melanoma Institute Australia
Sydney , 2060, Australia
Helios Klinikum Erfurt
Erfurt , 99089, Germany
Universitaetsklinikum Essen (AoR)
Essen , 45147, Germany
Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie
Freiburg , 79104, Germany
Medizinische Hochschule Hannover (MHH)
Hannover , 30625, Germany
Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel Hautkrebszentrum Kiel
Kiel , 24105, Germany
Universitaetsklinikum Leipzig
Leipzig , 04103, Germany
Universitaetsmedizin der Johannes Gutenberg Universitat Mainz KoeR
Mainz , 55131, Germany
Universitaetsklinikum Mannheim GmbH
Mannheim , 68167, Germany
Klinikum Nürnberg Nord
Nürnberg , 90419, Germany
University Hospital Tuebingen
Tübingen , 72076, Germany
Klinikum der Julius-Maximilians-Universität Würzburg
Würzburg , 97080, Germany
Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Tumori Giovanni Paolo Ii
Bari , 70124, Italy
Azienda ospedaliera universitaria Bologna
Bologna , 40138, Italy
Fondazione del Piemonte per l'Oncologia, Istituto di Candiolo (IRCCs)
Candiolo , 10060, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumpori (IRST)
Meldola , 47014, Italy
Istituto Nazionale Tumori Fondazione Pascale - IRCCS · S.C. Oncologia Medica Melanoma, Immunoterapia Oncologica e Terapie Innovative
Napoli , 80131, Italy
IOV - Istituto Oncologico Veneto - IRCCS
Padova , 35128, Italy
Universita di Siena -Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
Siena , 53100, Italy
AOU Citta della Salute e della Scienza di Torino
Turin , 10126, Italy
Uniwersyteckie Centrum Kliniczne
Gdańsk , 80214, Poland
Szpital Specjalistyczny im. Luwika Rydygiera w Krakowie Sp. z o.o.
Kraków , 31-82, Poland
Centrum Onkologii Ziemii Lubelskiej im. sw. Jana z Dukli
Lublin , 20-09, Poland
Zachodniopomorskie Centrum Onkologii
Szczecin , 71-73, Poland
Specjalistyczny Szpital Onkologiczny NU-MED
Tomaszów Mazowiecki , 97-20, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw , 02-78, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Łódź , 93-51, Poland
Hospital Teresa Herrera (CHUAC)
A Coruña , 15009, Spain
Hospital Universitari Germans Trias i Pujol (HUGTP)
Badalona , 8916, Spain
Hospital Clinic de Barcelona
Barcelona , 08036, Spain
Hospital De La Santa Creu I Sant Pau
Barcelona , 08041, Spain
Institut Català d'Oncologia l'Hospitalet
Barcelona , 08907, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar , 30120, Spain
Hospital General Universitario Gregorio Maranon
Madrid , 28007, Spain
MD Anderson Cancer Center
Madrid , 28033, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Madrid , 28222, Spain
Hospital Universitario Marques De Valdecilla
Santander , 39008, Spain
Complejo Hospitalario Universitario De Santiago De Compostela
Santiago De Compostela , 15706, Spain
Hospital Universitario Virgen del Rocio
Sevilla , 41013, Spain
Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
Valencia , 46026, Spain
The Christie - The Christie NHS Foundation Trust
Manchester , M20 4, United Kingdom
Royal Cornwall Hospital
Truro , TR1 3, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 2

Estimated Enrollment:

180

Study ID:

NCT04526899

Recruitment Status:

Recruiting

Sponsor:


BioNTech SE

How clear is this clinincal trial information?

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