Safety and Efficacy of Intravenous Cemiplimab Plus BNT116 Versus Cemiplimab Alone in Advanced Non-Small Cell Lung Cancer in Adult Participants With PD-L1 ≥ 50%

Study Overview
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Brief Summary
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The study is researching an investigational drug, called BNT116, in combination with cemiplimab. BNT116 and cemiplimab will each be called a study drug, and together be called study drugs in this form. The study is focused on patients who have advanced non-small cell lung cancer (NSCLC). The aims of the study are to see how safe and tolerable BNT116 is in combination with cemiplimab and to see how effective BNT116 in combination with cemiplimab is compared to cemiplimab by itself at treating your cancer. The study is looking at several other research questions, including: What side effects may happen from receiving the study drugs How much study drug is in your blood at different times Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects)

Official Title
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A Phase 2 Study of Cemiplimab (Anti-PD-1 Antibody) in Combination With BNT116 (FixVac Lung) Versus Cemiplimab Monotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With Tumors Expressing PD-L1 ≥50%

Conditions
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Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: BNT116
* Drug: Cemiplimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Participants with non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic) disease who received no prior systemic treatment for recurrent or metastatic NSCLC Availability of an archival or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample as defined in the protocol. Expression of Programmed cell death ligand-1 (PD-L1) in ≥50% of tumor cells stained using the VENTANA PD-L1 (SP263) Assay as performed by a central laboratory Participants must have at least 1 radiographically measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Key Exclusion Criteria Participants who have never smoked, defined as smoking ≤100 cigarettes in a lifetime Active or untreated brain metastases or spinal cord compression. Participants are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment Participants with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase 1 (ROS1) fusions Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment Participants with history of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years Prior splenectomy Uncontrolled infection with human immunodeficiency virus (HIV), HBV or hepatitis C infection (HCV); or diagnosis of immunodeficiency as defined in the protocol Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-related treatment-emergent adverse events (imTEAEs) Participants requiring corticosteroid therapy (>5 mg prednisone/day or equivalent) within 14 days of randomization Another malignancy that is progressing or requires treatment, with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other localized tumor that has been treated, and the participant is deemed to be in complete remission for at least 2 years prior to enrollment, and no additional therapy is required during the study period Documented or suspected ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as defined in the protocol Patients who have received prior systemic therapies for NSCLC are excluded with the exception of the following: Adjuvant or neoadjuvant platinum-based doublet chemotherapy (after surgery and/or radiation therapy) if recurrent or metastatic disease develops more than 6 months after completing therapy as long as toxicities have resolved to CTCAE grade ≤1 or baseline with the exception of alopecia and peripheral neuropathy. Anti-PD-(L)1 with or without LAG-3 as an adjuvant or neoadjuvant therapy as long as the last dose is >12 months prior to enrollment. Prior exposure to other immunomodulatory or vaccine therapies as an adjuvant or neoadjuvant therapy such as anti-cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) antibodies as long as the last dose is >6 months prior to enrollment History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment. Hypersensitivity to cemiplimab or any of its excipients or contraindicated to cemiplimab per approved local labeling. Note: Other protocol-defined Inclusion/Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Cemiplimab<br>Arm A: Cemiplimab is administered by IV infusion Q3W | Drug: Cemiplimab<br>* Cemiplimab is administered Q3W by IV infusion<br>* Other names: Libtayo;|
| Experimental: Phase 2: BNT116 + Cemiplimab<br>Arm B: BNT116 is administered by IV injection. Cemiplimab is administered by IV infusion Q3W. | Drug: BNT116<br>* BNT116 is administered by IV injection.<br>Drug: Cemiplimab<br>* Cemiplimab is administered Q3W by IV infusion<br>* Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) as assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) | Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR) | Up to 136 weeks from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by investigator assessment | Proportion of patients with a best overall response of confirmed CR or PR | Up to 136 weeks from randomization | 
| Duration of Response (DOR) as assessed by BIRC using RECIST 1.1 | The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR | Up to 3 years from last patient randomized | 
| DOR by investigator assessment | The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR | Up to 3 years from last patient randomized | 
| Progression Free Survival (PFS) as assessed by BIRC using RECIST 1.1 | The time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier | Up to 3 years from last patient randomized | 
| PFS by investigator assessment | The time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier | Up to 3 years from last patient randomized | 
| Overall Survival (OS) | The time from enrollment to the date of death due to any cause | Up to 3 years from last patient randomized | 
| Incidence of treatment-emergent adverse events (TEAEs) | A TEAE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. | Up to 3 years | 
| Incidences of serious adverse events (SAEs) | An SAE is any untoward medical occurrence that at any dose: Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger) Is life-threatening Requires in-patient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Is an important medical event | Up to 3 years | 
| Incidences of deaths |  | Up to 3 years | 
| Incidences of laboratory abnormalities | According to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Causality grading system (≥ Grade 3 or higher) | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Vaccine, Immunotherapy, Programmed cell death ligand-1 (PD-L1) monoclonal antibody, Treatment naïve Advanced Non-Small Cell Lung Cancer (NSCLC), EMPOWERVAX Lung 1