A Trial to Learn How the Cancer Vaccine BNT116 in Combination With Cemiplimab Works and How Safe the Combination is in Adults With Advanced Non-small Cell Lung Cancer (EMPOWERVAX Lung 1)

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%

This 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". The study is focused on patients who have advanced non-small cell lung cancer (NSCLC).

The aims of this 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 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 the 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)

Key Inclusion Criteria

1. 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
2. Availability of an archival or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample as defined in the protocol.
3. Expression of Programmed cell death ligand-1 (PD-L1) ≥50%, as described in the protocol.
4. 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
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

Key Exclusion Criteria

1. Participants who have never smoked, defined as smoking ≤100 cigarettes in a lifetime

2. 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

3. 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

4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment

5. 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

6. Prior splenectomy

7. Uncontrolled infection with human immunodeficiency virus (HIV), HBV or hepatitis C infection (HCV); or diagnosis of immunodeficiency as defined in the protocol

8. 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)

9. Participants requiring corticosteroid therapy (>5 mg prednisone/day or equivalent) within 14 days of randomization

10. Another malignancy that is progressing or requires treatment, except for 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

11. Documented or suspected ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as defined in the protocol

12. Patients who have received prior systemic therapies for NSCLC are excluded except for of the following:

    1. 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 if toxicities have resolved to CTCAE grade ≤1 or baseline except for alopecia and peripheral neuropathy.
    2. 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.
    3. 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 if the last dose is >6 months prior to enrollment

13. 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.

14. Hypersensitivity to cemiplimab or BNT116 or any of their excipients, or contraindicated to cemiplimab per approved local labeling.

15. Patients treated with immunostimulatory agents that may influence the efficacy of the investigational medicinal products (IMPs) are not allowed if they received such agents within 6 weeks or five halve lives of the drug.

Note: Other protocol-defined Inclusion/Exclusion criteria apply