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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Apr 2024 → ongoing

Decision date (initial)

2023-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2023-503221-19-00

ClinicalTrials.gov

NCT05557591

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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

Secondary objectives 2

1. To assess other anti-tumor activities of combination of cemiplimab and BNT116 and cemiplimab monotherapy, as measured by ORR per investigator assessment, DOR, PFS, and OS.
2. To further examine the safety and tolerability of combination of cemiplimab and BNT116 and cemiplimab monotherapy.

Conditions and MedDRA coding

Advanced Non-Small Cell Lung Cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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
6. Other protocol-defined inclusion criteria apply

Exclusion criteria 17

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: 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.
13. Patients who have received prior systemic therapies for NSCLC are excluded with the exception of the following: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.
14. Patients who have received prior systemic therapies for NSCLC are excluded with the exception of the following: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
15. 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.
16. Hypersensitivity to cemiplimab or any of its excipients or contraindicated to cemiplimab per approved local labeling.
17. Other protocol-defined Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 10

1. ORR by investigator assessment
2. Duration of Response (DOR) as assessed by BIRC using RECIST 1.1
3. DOR by investigator assessment
4. Progression Free Survival (PFS) as assessed by BIRC using RECIST 1.1
5. PFS by investigator assessment
6. Overall Survival (OS)
7. Incidence of treatment-emergent adverse events (TEAEs)
8. Incidences of serious adverse events (SAEs)
9. Incidences of deaths
10. Incidences of laboratory abnormalities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 14

Locations

3 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications