A trial to learn if odronextamab is safe and well-tolerated and how well it works compared to rituximab combined with different types of chemotherapy for adult participants with untreated follicular lymphoma

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

23 Jan 2024 → ongoing

Decision date (initial)

2023-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceutical Inc

External identifiers

EU CT number

2022-502660-20-00

ClinicalTrials.gov

NCT06091254

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

Part 1 (Safety Run-in): Assess the safety, tolerability, and dose-limiting toxicities (DLTs) of odronextamab in participants with previously untreated follicular lymphoma (FL)

Part 2 (Randomized Phase): To compare the efficacy of odronextamab versus investigator’s choice chemotherapy in participants with previously untreated FL as measured by complete response at 30 months (CR30) per independent central review

Secondary objectives 13

1. Part 1: To characterize the pharmacokinetics (PK) of odronextamab
2. Part 1: To assess the immunogenicity of odronextamab
3. Part 1: To evaluate the preliminary anti-tumor activity of odronextamab
4. Part 2: To compare the efficacy per independent central review between odronextamab monotherapy and investigator’s choice chemotherapy as measured by: progression-free survival (PFS)
5. Part 2: To compare the efficacy of odronextamab monotherapy versus investigator’s choice chemotherapy as measured by OS
6. Part 2: To evaluate the treatment effects on patient-reported physical function between odronextamab monotherapy and investigator’s choice chemotherapy utilizing European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
7. Part 2: To assess additional measures of efficacy of odronextamab compared to investigator’s choice chemotherapy
8. Part 2: To evaluate safety and tolerability of odronextamab compared to investigator’s choice chemotherapy
9. Part 2: To evaluate the PK of odronextamab
10. Part 2: To assess the immunogenicity of odronextamab
11. Part 2: To evaluate the effect of odronextamab compared to investigator’s choice chemotherapy impact on patient-reported outcomes (PROs), including health related quality of life (HRQoL), as measured by the validated instruments European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), Functional Assessment of Cancer Therapy – Lymphoma, lymphoma subscale (FACT-LymS), Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and EuroQoL-5 Dimension-5 Level Scale (EQ-5D-5L)
12. Part 2: To evaluate the patient-reported overall impact of treatment toxicity using the GP5 item of the validated Functional Assessment of Cancer - General (FACT-G) questionnaire
13. Part 2: To compare the efficacy per independent central review between odronextamab monotherapy and investigator’s choice” chemotherapy as measured by: event free survival (EFS)

Conditions and MedDRA coding

Follicular lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnoses of cluster of differentiation 20^+ (CD20^+) FL Grade 1-3a, stage II bulky or stage III / IV
2. Need for treatment as described in the protocol
3. Have measurable disease on cross-sectional imaging documented by diagnostic imaging Computed tomography (CT) or Magnetic resonance imaging (MRI)
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5. Adequate bone marrow function and hepatic function as described in the protocol
6. NOTE: Other protocol defined inclusion criteria apply

Exclusion criteria 6

1. Central nervous system (CNS) lymphoma or leptomeningeal lymphoma
2. Histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
3. Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), Grade 3b follicular lymphoma, chronic lymphocytic leukemia, or small lymphocytic lymphoma
4. Treatment with any systemic anti-lymphoma therapy
5. Infections and allergy/hypersensitivity to study drug or excipient as described in the protocol
6. NOTE: Other protocol defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Incidence of dose-limiting toxicities (DLTs) for odronextamab
2. Part 1: Incidence of treatment-emergent adverse events (TEAEs) of odronextamab
3. Part 1: Severity of TEAEs of odronextamab
4. Part 2: CR30 as assessed by independent central review

Secondary endpoints 27

1. Part 1: Concentrations of odronextamab in serum
2. Part 1:Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration
3. Part 1: Magnitude of ADAs to odronextamab over the study duration
4. Part 1: Objective response as assessed by the investigator
5. Part 2: Progression-free survival (PFS) as assessed by independent central review
6. Part 2: Event-free survival (EFS) as assessed by independent central review
7. Part 2: OS
8. Part 2: Overall mean change in physical function [European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC-QLQ-C30)]
9. Part 2: CR30 as assessed by local investigator
10. Part 2: PFS as assessed by local investigator
11. Part 2: EFS as assessed by local investigator
12. Part 2: Objective response assessed by local investigator
13. Part 2: Objective response assessed by independent central review
14. Part 2: Duration of response (DOR) assessed by independent central review
15. Part 2: DOR assessed by local investigator
16. Part 2: Time to next anti-lymphoma treatment (TTNT)
17. Part 2: Incidence of TEAEs
18. Part 2: Severity of TEAEs
19. Part 2: Odronextamab concentrations in serum during the induction period
20. Part 2: Odronextamab concentrations in serum during the maintenance period
21. Part 2: Incidence of ADAs to odronextamab over the study duration
22. Part 2: Magnitude of ADAs to odronextamab over the study duration
23. Part 2: Overall mean changes in scores of patient reported outcomes (PROs), as measured by the validated instruments EORTCQLQ- C30
24. Part 2: Overall mean changes in scores of PROs, as measured by the validated instruments Functional Assessment of Cancer Therapy–Lymphoma (FACT-LymS)
25. Part 2: Overall mean changes in scores of PROs, as measured by the validated instruments EuroQol-5 Dimension-5 Level Scale (EQ-5D- 5L)
26. Part 2: Change in PGIS and PGIC
27. Part 2: Change in score of GP5 item in the participant population

Investigational products

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

Test 2

Comparator 8

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

Head of EU Regulatory Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Head of EU Regulatory Affairs

Third parties 9

Locations

8 EU/EEA countries · 87 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 216 files

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

Application history

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