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%

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05557591

Collaborator

BioNTech SE (Industry)

107

Enrollment

Arms

56.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Primary objective of phase 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:

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.
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:

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Non-Small Cell Lung Cancer	Drug: BNT116 Drug: Cemiplimab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

107 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 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%

Anticipated Study Start Date :

Jan 5, 2023

Anticipated Primary Completion Date :

Jun 4, 2027

Anticipated Study Completion Date :

Sep 8, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: BNT116 + Cemiplimab BNT116 is administered by intravenous (IV) injection. Cemiplimab is administered by IV infusion Q3W.	Drug: BNT116 BNT116 is administered by IV injection. Drug: Cemiplimab Cemiplimab is administered Q3W by IV infusion Other Names: REGN2810 Libtayo
Experimental: Phase 2: Cemiplimab Arm A: Cemiplimab is administered by IV infusion Q3W	Drug: Cemiplimab Cemiplimab is administered Q3W by IV infusion Other Names: REGN2810 Libtayo
Experimental: Phase 2: BNT116 + Cemiplimab Arm B: BNT116 is administered by IV injection. Cemiplimab is administered by IV infusion Q3W.	Drug: BNT116 BNT116 is administered by IV injection. Drug: Cemiplimab Cemiplimab is administered Q3W by IV infusion Other Names: REGN2810 Libtayo

Arm

Intervention/Treatment

Experimental: Phase 1: BNT116 + Cemiplimab

BNT116 is administered by intravenous (IV) injection. Cemiplimab is administered by IV infusion Q3W.

Drug: BNT116

BNT116 is administered by IV injection.

Drug: Cemiplimab

Cemiplimab is administered Q3W by IV infusion

Other Names:

REGN2810

Libtayo

Experimental: Phase 2: Cemiplimab

Arm A: Cemiplimab is administered by IV infusion Q3W

Drug: Cemiplimab

Cemiplimab is administered Q3W by IV infusion

Other Names:

REGN2810

Libtayo

Experimental: Phase 2: BNT116 + Cemiplimab

Arm B: BNT116 is administered by IV injection. Cemiplimab is administered by IV infusion Q3W.

Drug: BNT116

BNT116 is administered by IV injection.

Drug: Cemiplimab

Cemiplimab is administered Q3W by IV infusion

Other Names:

REGN2810

Libtayo

Outcome Measures

Primary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs) [Up to 136 Weeks]
Phase 1 TEAEs as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (Grade 3 or higher)
Incidences of serious adverse events (SAEs) [Up to 136 Weeks]
Phase 1 SAEs as assessed by the NCI-CTCAE grading system
Incidences of deaths [Up to 56 months]
Phase 1
Incidences of laboratory abnormalities [Up to 136 Weeks]
Phase 1 Laboratory abnormalities as assessed by the NCI-CTCAE grading system (≥ Grade 3 or higher)
Objective response rate (ORR) [Up to 136 Weeks]
Phase 2 ORR is defined as proportion of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR); ORR as assessed by the Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Tumor Burden Reduction [Baseline to Week 27]
Phase 2: Tumor burden reduction is defined as percentage change from baseline per RECIST V 1.1. criteria and as assessed by the IRC

Secondary Outcome Measures

Tumor Burden Reduction [Baseline to Week 27]
Phase 1 and Phase 2 Tumor burden reduction as defined above and as assessed by the investigator per RECIST v 1.1. criteria
ORR [Up to 136 Weeks]
Phase 1 and Phase 2 ORR is defined as noted above and assessed by the investigator using RECIST V 1.1 criteria
Duration of Response (DoR) [Baseline to 136 Weeks]
Phase 1 DOR as assessed by the investigator is defined as the time from first response of CR or PR to first radiographic progression or death due to any cause for participants with confirmed CR or PR.
Progression Free Survival (PFS) [Baseline to 136 Weeks]
Phase 1 PFS is defined as the time from enrollment to the date of the first radiographic progression or death due to any cause, whichever occurred earlier; PFS as assessed by the investigator
Overall Survival (OS) [Baseline to 56 months]
Phase 1 and Phase 2 OS is defined as the time from enrollment to the date of death due to any cause
Duration of Response [Baseline to 136 Weeks]
Phase 2 DOR is defined as 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; DoR as assessed by the IRC and the investigator
PFS [Baseline to 136 weeks]
Phase 2 PFS is defined as above and assessed by the IRC and the investigator
Incidence of TEAEs [Up to 136 weeks]
Phase 2 TEAE's as defined above
Incidences of serious adverse events (SAEs) [Up to 136 weeks]
Phase 2 SAEs as defined above
Incidences of deaths [Up to 56 months]
Phase 2
Incidences of laboratory abnormalities [Up to 136 weeks]
Phase 2 Laboratory abnormalities as defined above

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

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
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 per protocol
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 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 therapies 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 such as anti-cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) antibodies as long as the last dose is >3 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.