Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in Patients With Lung Cancer

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

20 Jul 2018 → 28 Feb 2025

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2024-515051-38-00

EudraCT number

2017-001311-36

ClinicalTrials.gov

NCT03409614

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Efficacy

Part 1: To compare the overall survival (OS) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) with tumors expressing PD-L1 in <50% of tumor cells.

Part 2: To compare the OS of cemiplimab/chemo-f with placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.

Secondary objectives 13

1. Part 1: To compare the progression free survival (PFS) and overall response rate (ORR) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in <50% of tumor cells.
2. Part 2: To compare the PFS and ORR of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.
3. Parts 1 and 2: To evaluate the safety and tolerability of cemiplimab/chemol/ ipi and/or cemiplimab/chemo-f compared to platinum-based doublet chemotherapy or placebo/chemo-f
4. Part 1 and 2: To evaluate the DOR of cemiplimab/chemo-l/ipi and/or cemiplimab/chemo-f compared to chemo-f or placebo/chemo-f in the firstline treatment of patients with advanced squamous or non-squamous NSCLC.
5. Parts 1 and 2: To compare quality of life (QOL) in patients with advanced squamous or non-squamous NSCLC receiving cemiplimab/chemo-l/ipi and cemiplimab/chemo-f compared to platinum-based doublet chemotherapy or placebo/chemo-f
6. Part 1: To evaluate the OS rate at 12 months, 18 months, and 24 months of cemiplimab/chemo-f and/or cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in <50% of tumor cells.
7. Part 2: To evaluate the OS rate at 12, 18, and 24 months of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.
8. Parts 1 and 2: To assess immunogenicity as measured by anti-drug antibodies (ADAs) for cemiplimab
9. Parts 1 and 2: To assess the predictive utility of baseline PD-L1 tumor expression levels on clinical response
10. Part 1: To characterize the pharmacokinetics (PK) of cemiplimab when administered in combination with ipilimumab or in combination with platinum-based doublet chemotherapy.
11. Part 2: To characterize the PK of cemiplimab when administered in combination with platinum-based doublet chemotherapy
12. Parts 1 and 2: To conduct exposure-response (E-R) analyses for relevant biomarkers (exploratory PK/pharmacodynamic analyses) and E-R analyses for safety and efficacy endpoints, as appropriate
13. Parts 1 and 2: Tumor mutation burden as assessed by the Foundation Medicine “FoundationOne®” panel, sample permitting

Conditions and MedDRA coding

Non-small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease if they have not received prior systemic treatment for recurrent or metastatic NSCLC
2. Availability of an archival (≤5 months) or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample from a metastatic or recurrent site, which has not previously been irradiated
3. Part 1 only: Expression of PD-L1 in <50% of tumor cells determined by a commercially available assay performed by the central laboratory
4. At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
6. Anticipated life expectancy of at least 3 months
7. Note: Other protocol defined Inclusion criteria may apply

Exclusion criteria 8

1. Part 1 only: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime
2. Active or untreated brain metastases or spinal cord compression
3. Patients 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(ROS1) fusions
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrolment
5. 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. 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 (irTEAEs)
7. Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization
8. Note: Other protocol defined Exclusion criteria may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival

Secondary endpoints 12

1. Progression-free survival
2. Objective response rate
3. Duration of Response (DOR)
4. Best overall response (BOR)
5. Incidence of Treatment-emergent adverse events (TEAEs)
6. Part 1 only: Incidence of Dose-limiting toxicities (DLTs)
7. Incidence of serious adverse events (SAEs)
8. Incidence of deaths
9. Incidence of laboratory abnormalities
10. Overall survival rate
11. Quality of life as measured by EORTC QLQ-C30
12. Quality of life as measured by EORTC QLQ-LC13

Investigational products

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

Test 6

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 8

Locations

4 EU/EEA countries · 16 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 26 files

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

Application history

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