Clinical Trials/NCT04526899

NCT04526899

Completed

Phase 2

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

BioNTech SE88 sites in 7 countries184 target enrollmentStarted: May 19, 2021Last updated: January 8, 2026

ConditionsMelanoma Stage III Melanoma Stage IV Unresectable Melanoma

InterventionsBNT111 Cemiplimab

DrugsBNT111 Cemiplimab

Overview

Phase: Phase 2
Status: Completed
Sponsor: BioNTech SE
Enrollment: 184
Locations: 88
Primary Endpoint: Arm 1: Objective Response Rate (ORR)

Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials Related News

Overview

Brief Summary

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

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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 v1.
•Patients must have confirmed disease progression on/after an approved anti-PD-1/PD-L1 regimen for melanoma as defined by RECIST v1.
•Previous exposure to approved anti-PD-1/PD-L1 containing regimen for at least 12 consecutive weeks and
•Current radiological progression to be confirmed by two scans 4 to 12 weeks apart. If progression is accompanied by new symptoms, or deterioration of performance status not attributed to toxicity, one scan is sufficient and
•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).

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 irAEs.
•Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
•Patients must have no known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T cell-negative severe combined immunodeficiency \[SCID\]) or combined T and B cell immunodeficiencies (e.g., T and -B negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency).
•Patients with uncontrolled type 1 diabetes mellitus or with uncontrolled adrenal insufficiency are not eligible.
•Patients must have no uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. Mild cancer-related immunodeficiency (such as immunodeficiency treated with gamma globulin and without chronic or recurrent infection) is allowed.
•Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable anti-viral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
•Patients with known hepatitis B virus (HBV) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of trial treatment.
•Patients who are known hepatitis C virus (HCV) antibody positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

Arms & Interventions

BNT111 + cemiplimab

Experimental

Intervention: BNT111 (Biological)

BNT111 + cemiplimab

Experimental

Intervention: Cemiplimab (Biological)

BNT111 monotherapy

Experimental

Intervention: BNT111 (Biological)

Cemiplimab monotherapy

Experimental

Intervention: Cemiplimab (Biological)

Outcomes

Primary Outcomes

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.

Secondary Outcomes

Arms 2 & 3: Objective Response Rate (ORR)(Up to 24 Months)
Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR)(Up to 24 Months)
Disease Control Rate (DCR) As Assessed by BICR(Up to 24 months)
Time to Response (TTR) As Assessed by BICR(Up to 24 months)
Progression-Free Survival (PFS) As Assessed by BICR(Up to 24 Months)
Objective Response Rate (ORR) As Assessed by the Investigator(Up to 24 months)
Duration of Response (DOR) As Assessed by the Investigator(Up to 24 Months)
Disease Control Rate (DCR) As Assessed by the Investigator(Up to 24 months)
Time to Response (TTR) As Assessed by the Investigator(Up to 24 months)
Progression-Free Survival (PFS) As Assessed by the Investigator(Up to 24 Months)
Arm 1: Overall Survival (OS)(Up to 48 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Up to 27 months)
Number of Participants With Immune-Related Adverse Events (irAE)(Up to 27 months)
Number of Participants Reporting Dose Reduction and Discontinuation Due to TEAE(Up to 27 months)
Change From Baseline in Laboratory Parameters Values: Hematology: Basophils(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Hematology: Eosinophils(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Hematocrit(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Hemoglobin(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Hematology: Lymphocytes(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Albumin(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alkaline Phosphatase(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alanine Aminotransferase(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Amylase(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Aspartate Aminotransferase(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Bilirubin(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatine Kinase(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatinine(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: C-Reactive Protein(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Activated Partial Thromboplastin Time(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Prothrombin Time(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Endocrine Tests: Thyroxine(From Baseline up to 25 months)
Change From Baseline in Laboratory Parameters Values: Urinalysis: pH(From Baseline up to 25 months)
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters(Up to 25 months)
Change From Baseline in Vital Signs Parameters: Systolic Blood Pressure(From Baseline up to 25 months)
Change From Baseline in Vital Signs Parameters: Diastolic Blood Pressure(From Baseline up to 25 months)
Change From Baseline in Vital Signs Parameters: Heart Rate(From Baseline up to 25 months)
Change From Baseline in Vital Signs Parameters: Respiratory Rate(From Baseline up to 25 months)
Change From Baseline in Vital Signs Parameters: Body Temperature(From Baseline up to 25 months)
Number of Participants With Clinically Significant Abnormalities in Vital Signs(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(From Baseline up to 25 months)
Change From Baseline in EORTC QLQ-C30 Functional Scales Score(From Baseline up to 25 months)
Changes From Baseline in EORTC QLQ-C30 Symptoms Scales Score(From Baseline up to 25 months)
Time to First Clinically Meaningful Deterioration in Global Health Status Score as Measured by EORTC QLQ-C30(Up to 25 months)
Time to First Clinically Meaningful Deterioration in Symptoms and Functioning as Measured by EORTC QLQ-C30(Up to 25 months)

Investigators

Sponsor

BioNTech SE

Sponsor Class

Industry

Responsible Party

Sponsor

Study Sites (88)

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