REGN5093 in Patients With MET-Altered Advanced Non-Small Cell 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

7 Jan 2020 → 4 Mar 2025

Decision date (initial)

2024-06-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-506248-18-00

EudraCT number

2019-001908-38

ClinicalTrials.gov

NCT04077099

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Others, Pharmacokinetic, Efficacy

Phase 1: To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5093 for determination of the maximum tolerated dose (MTD) and/or definition of the recommended phase 2 dose (RP2D) of REGN5093 in patients with MET-altered non-small cell lung cancer (NSCLC)
Phase 2: To assess preliminary anti-tumor activity of REGN5093 as measured by the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Secondary objectives 5

1. Phase 1: To assess preliminary anti-tumor activity of REGN5093 as measured by the ORR per RECIST 1.1
2. Phase 2: To assess the safety and tolerability of REGN5093 in each expansion cohort
3. Phase 2: To assess REGN5093 PK and concentrations in serum
4. Phase 1 and phase 2: To assess immunogenicity as measured by anti-drug antibodies (ADA) to REGN5093
5. Phase 1 and phase 2: To evaluate other measures of preliminary anti-tumor activity

Conditions and MedDRA coding

MET-altered non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically confirmed NSCLC that is at advanced stage. Advanced is defined as unresectable or metastatic disease. Patients must have exhausted all approved available therapies appropriate for the patient.
2. Has available archival tumor tissue, unless discussed with the medical monitor.
3. Willing to provide tumor tissue from newly obtained biopsy. Newly obtained biopsies at screening are required unless medically contra-indicated and discussed with the medical monitor. For patients in expansion cohorts, biopsies should be taken from tumor site which has not been irradiated previously and is not the only measurable target lesion.
4. Previously documented presence of MET alterations: either MET-exon14 gene mutation and/or MET gene amplification, and/or elevated MET protein expression, as defined in the protocol.
5. Note: Other protocol defined Inclusion criteria apply.

Exclusion criteria 7

1. Has received treatment with an approved systemic therapy or has participated in any study of an investigational agent or investigational device within 2 weeks or 5 half-lives of the prior treatment whichever is shorter with a minimum of 7 days from the first dose of study therapy
2. Has not yet recovered (i.e. grade ≤1 or baseline) from any acute toxicities resulting from prior therapy except as described in the protocol
3. Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered (i.e. grade ≤1 or baseline) from AEs, except for laboratory changes as described in the protocol and patients with grade ≤2 neuropathy
4. For expansion cohorts only: prior treatment with MET-targeted biologic therapy (function-blocking antibodies or ADCs)
5. For expansion cohorts only (except cohort 1A) prior treatment with any MET-targeted agent including small molecule tyrosine kinase inhibitors eg, crizotinib, capmatinib, tepotinib, as defined in the protocol
6. Untreated or active primary brain tumor, CNS metastases, leptomeningeal disease or spinal cord compression as defined in the protocol
7. Note: Other protocol defined Exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Phase 1: Number of patients with Dose Limiting Toxicities
2. Phase 1: Incidence and severity of treatment-emergent adverse events
3. Phase 1: Incidence and severity of adverse events of special interest (AESIs)
4. Phase 1: Incidence and severity of serious adverse events (SAEs)
5. Phase 1: Incidence and severity of grade ≥3 laboratory abnormalities
6. Phase 1: REGN5093 concentrations in serum over time
7. Phase 2: Objective response rate (ORR) per RECIST 1.1

Secondary endpoints 12

1. Phase 1: ORR per RECIST 1.1
2. Phase 2: Incidence and severity of TEAEs
3. Phase 2: Incidence and severity of AESIs
4. Phase 2: Incidence and severity of SAEs
5. Phase 2: Incidence and severity of grade ≥3 laboratory abnormalities
6. Phase 2: REGN5093 Pharmacokinetics (PK)
7. Phase 2: REGN5093 concentrations in serum over time
8. Phase 1 and 2: Duration of response (DOR) per RECIST 1.1.
9. Phase 1 and 2: Disease control rate (DCR) per RECIST 1.1.
10. Phase 1 and 2: Progression free survival (PFS) per RECIST 1.1.
11. Phase 1 and 2: Overall survival (OS)
12. Phase 1 and 2: Immunogenicity as measured by Anti-drug antibodies (ADA) to REGN5093

Investigational products

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

Test 1

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 7

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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