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%

• Status: Not yet recruiting
• Trial end date: 2027-07-21
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective of phase 1:

1. To assess the safety and tolerability of BNT116 alone and in combination with cemiplimab in first-line treatment of participants with advanced non-small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand-1 (PD-L1) in ≥ 50% of tumor cells.

Primary objectives of phase 2:

1. To assess the objective response rate (ORR) per independent review committee (IRC) of combination of cemiplimab and BNT116 and cemiplimab monotherapy in the first-line treatment of participants with advanced NSCLC whose tumors express PD-L1 in ≥ 50% of tumor cells.

2. To assess the tumor burden reduction at week 27 per IRC of combination of cemiplimab and BNT116 and cemiplimab monotherapy in the first-line treatment of participants with advanced NSCLC whose tumors express PD-L1 in ≥ 50% of tumor cells.

Secondary objective of phase 1:

To assess anti-tumor activities as measured by ORR, tumor burden reduction at week 27, duration of response (DOR), progression free survival (PFS), and overall survival (OS).

Secondary objectives of phase 2:

1. To assess other anti-tumor activities of combination of cemiplimab and BNT116 and cemiplimab monotherapy, as measured by tumor burden reduction at week 27 and ORR per investigator assessment, DOR, PFS, and OS.

2. To assess the safety and tolerability of combination of cemiplimab and BNT116 and cemiplimab monotherapy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Regeneron Pharmaceuticals
• Collaborator: BioNTech SE
• Treatments: Cemiplimab

Criteria

Key Inclusion Criteria

1. Participants with non-squamous or squamous histology with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or metastatic disease

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) in ≥50% of tumor cells stained using the VENTANA PD-L1 (SP263) Assay as performed by a central laboratory

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 per protocol

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 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, 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

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 therapies are excluded with the exception 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 as long as toxicities have resolved to CTCAE grade ≤1 or baseline with the exception of 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 such as anti-cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) antibodies as long as the last dose is >3 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.

Note: Other protocol-defined Inclusion/Exclusion criteria apply