A Trial to Learn if Odronextamab Combined with Chemotherapy is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined with Chemotherapy for Adult Participants with 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

1 Feb 2024 → ongoing

Decision date (initial)

2023-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceutical Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Part 1
Assess the safety, tolerability, and dose limiting toxicities (DLTs) of odronextamab in combination with chemotherapy in participants with previously untreated follicular lymphoma (FL) and participants with relapsed or refractory (R/R) FL (Part 1A only), and to determine an optimal dosing regimen of odronextamab (Part 1B) in previously untreated participants with FL to combine with CHOP/CVP in Part 2.

Part 2
To compare the efficacy of odronextamab in combination with chemotherapy versus rituximab in combination with chemotherapy in participants with previously untreated FL as measured by complete response rate at 30 months (CR30) per independent central review.

Secondary objectives 12

1. Part 1: To characterize the pharmacokinetics (PK) of odronextamab in combination with chemotherapy
2. Part 1: To assess the immunogenicity of odronextamab in combination with chemotherapy
3. Part 1: To evaluate the preliminary anti-tumor activity of odronextamab in combination with chemotherapy
4. Part 2: To compare the efficacy per independent central review between odronextamab in combination with chemotherapy versus rituximab in combination with chemotherapy as measured by: Progression-free survival (PFS)
5. Part 2: To compare the efficacy of odronextamab in combination with chemotherapy versus rituximab in combination with chemotherapy as measured by CR30 per investigator
6. Part 2: To compare changes over time in patient reported physical functioning between odronextamab in combination with chemotherapy versus rituximab in combination with chemotherapy
7. Part 2: To compare additional measures of efficacy of odronextamab in combination with chemotherapy compared to rituximab in combination with chemotherapy.
8. Part 2: To evaluate safety and tolerability of odronextamab in combination with chemotherapy compared to rituximab in combination with chemotherapy
9. Part 2: To evaluate the PK of odronextamab in combination with chemotherapy
10. Part 2: To assess the immunogenicity of odronextamab in combination with chemotherapy.
11. Part 2: To evaluate the impact of odronextamab in combination with chemotherapy compared to rituximab in combination with chemotherapy on changes over time in patient reported outcomes, including health related quality of life (HRQoL), functioning (other than physical functioning) and symptoms
12. Part 2: To evaluate the overall impact of treatment toxicity using the Global Population item 5 (GP5 Item) of the validated FACT-G (Functional Assessment of Cancer Therapy-General) questionnaire

Conditions and MedDRA coding

Follicular lymphoma

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 6

1. Participants with central nervous system lymphoma or leptomeningeal lymphoma
2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
3. Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma
4. Recent major surgery and history or organ transplantation
5. A malignancy other than NHL unless the participant is adequately and definitively treated and any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, 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 in combination with chemotherapy
2. Part 1: Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy
3. Part 1: Severity of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy
4. Part 2: Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)

Secondary endpoints 30

1. Part 1 and 2: Odronextamab concentrations in serum when administered with chemotherapy
2. Part 1 and 2: Odronextamab concentrations in serum when administered as monotherapy
3. Part 1 and 2: Incidence of anti-odronextamab antibodies (ADAs)
4. Part 1 and 2: Titers of ADAs to odronextamab
5. Part 1 and 2: Incidence of neutralizing antibodies (NAb) to odronextamab
6. Part 1: Best overall response (BOR) as assessed by the investigator
7. Part 2: Progression free survival (PFS) as assessed by ICR
8. Part 2: Event-free survival (EFS) as assessed by ICR
9. Part 2: CR30 as assessed by local investigator
10. Part 2: Change in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30)
11. Part 2: PFS as assessed by local investigator
12. Part 2: EFS as assessed by local investigator
13. Part 2: Overall Survival (OS)
14. Part 2: Best Overall response (BOR) as assessed by local investigator
15. Part 2: BOR as assessed by ICR
16. Part 2: Duration of response (DOR) assessed by ICR
17. Part 2: DOR as assessed by local investigator
18. Part 2: Time to next anti-lymphoma treatment (TTNT)
19. Part 2: Incidence of TEAEs
20. Part 2: Severity of TEAEs
21. Part 2: Change in patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30
22. Part 2: Change in cancer disease as measured by EORTC-QLQ-C30
23. Part 2: Change in treatment related symptoms as measured by EORTC-QLQ-C30
24. Part 2: Change in patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)
25. Part 2: Change in treatment-related symptoms as measured by the FACT-LymS
26. Part 2: Change in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
27. Part 2: Change in patient-reported treatment side effects burden per Functional Assessment of Cancer Therapy–General Global Population Item 5 (FACT-5 GP5)
28. Part 2: Change in Patient Global Impression of Severity (PGIS)
29. Part 2: Change in Patient Global Impression of Change (PGIC)
30. Part 2: Change in score of the FACT-G GP5 item in the patient population

Investigational products

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

Test 2

Comparator 2

Auxiliary 5

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 EU Regulatory

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Head EU Regulatory

Third parties 9

Locations

8 EU/EEA countries · 94 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 214 files

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

Application history

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