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 (OLYMPIA-2)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Follicular Lymphoma (FL)

Treatments: Drug: Odronextamab; Drug: Vincristine; Drug: Rituximab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Prednisone/Prenisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT06097364

R1979-ONC-2075

2022-502113-28-00 (Other Identifier)

Details and patient eligibility

About

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma. Follicular lymphoma is a type of non-Hodgkin lymphoma or NHL. Participants with follicular lymphoma that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory") are eligible to take part only in Part 1A of the study.

This study is made up of 3 parts: Part 1A (non-randomized), Part 1B and Part 2 (randomized - controlled).

The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy to be used in Part 2 of the study.

The aim of Part 2 of the study is to assess how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab and chemotherapy (the current standard-of-care for NHL). Standard-of-care means the usual medication expected and used when receiving treatment for a condition.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
• The impact from the study drug on quality-of-life and ability to complete routine daily activities

Enrollment: 733 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV

   1. For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL
   2. For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5
   3. For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5

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.

Key Exclusion Criteria:

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.

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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733 participants in 4 patient groups

Odronextamab + Chemotherapy

Experimental group

Description:

Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.

Treatment:

Drug: Prednisone/Prenisolone

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Odronextamab

Rituximab + Chemotherapy

Active Comparator group

Description:

In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.

Treatment:

Drug: Prednisone/Prenisolone

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Vincristine

Drug: Rituximab

Drug: Odronextamab

Odronextamab + Chemotherapy + Maintenance

Experimental group

Description:

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy \[CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)\], followed by odronextamab monotherapy maintenance.

Treatment:

Drug: Vincristine

Drug: Odronextamab

Odronextamab + Chemotherapy + No maintenance

Experimental group

Description:

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.

Treatment:

Drug: Vincristine

Drug: Odronextamab