Phase 2
Completed N=184
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
Melanoma Stage III · Melanoma Stage IV · Unresectable Melanoma
Source: ClinicalTrials.gov NCT04526899 ↗
Enrolled (actual)
184
Serious AEs
27.2%
Results posted
Dec 2025
Primary outcomePrimary: Arm 1: Objective Response Rate (ORR) — 18.0 percentage of participants — p=0.0148
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Arm 1: Objective Response Rate (ORR) |
18.0 | 0.0148 sig |
| SECONDARY Arms 2 & 3: Objective Response Rate (ORR) |
— | — |
| SECONDARY Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) |
— | — |
| SECONDARY Disease Control Rate (DCR) As Assessed by BICR |
— | — |
| SECONDARY Time to Response (TTR) As Assessed by BICR |
— | — |
| SECONDARY Progression-Free Survival (PFS) As Assessed by BICR |
— | — |
| SECONDARY Objective Response Rate (ORR) As Assessed by the Investigator |
— | — |
| SECONDARY Duration of Response (DOR) As Assessed by the Investigator |
— | — |
| SECONDARY Disease Control Rate (DCR) As Assessed by the Investigator |
— | — |
| SECONDARY Time to Response (TTR) As Assessed by the Investigator |
— | — |
| SECONDARY Progression-Free Survival (PFS) As Assessed by the Investigator |
— | — |
| SECONDARY Arm 1: Overall Survival (OS) |
— | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
— | — |
| SECONDARY Number of Participants With Immune-Related Adverse Events (irAE) |
— | — |
| SECONDARY Number of Participants Reporting Dose Reduction and Discontinuation Due to TEAE |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Hematology: Basophils |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Hematology: Eosinophils |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Hematocrit |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Hemoglobin |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Hematology: Lymphocytes |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Albumin |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alkaline Phosphatase |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Alanine Aminotransferase |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Amylase |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Aspartate Aminotransferase |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Bilirubin |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatine Kinase |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: Creatinine |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Clinical Chemistry: C-Reactive Protein |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Activated Partial Thromboplastin Time |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Coagulation Factors: Prothrombin Time |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Endocrine Tests: Thyroxine |
— | — |
| SECONDARY Change From Baseline in Laboratory Parameters Values: Urinalysis: pH |
— | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters |
— | — |
| SECONDARY Change From Baseline in Vital Signs Parameters: Systolic Blood Pressure |
— | — |
| SECONDARY Change From Baseline in Vital Signs Parameters: Diastolic Blood Pressure |
— | — |
| SECONDARY Change From Baseline in Vital Signs Parameters: Heart Rate |
— | — |
| SECONDARY Change From Baseline in Vital Signs Parameters: Respiratory Rate |
— | — |
| SECONDARY Change From Baseline in Vital Signs Parameters: Body Temperature |
— | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Vital Signs |
— | — |
| SECONDARY 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 |
— | — |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Functional Scales Score |
— | — |
| SECONDARY Changes From Baseline in EORTC QLQ-C30 Symptoms Scales Score |
— | — |
| SECONDARY Time to First Clinically Meaningful Deterioration in Global Health Status Score as Measured by EORTC QLQ-C30 |
— | — |
| SECONDARY Time to First Clinically Meaningful Deterioration in Symptoms and Functioning as Measured by EORTC QLQ-C30 |
— | — |
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 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
- 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) = 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., ei
Data sourced from ClinicalTrials.gov (NCT04526899). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.