A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma

Genmab

Status and phase: Enrolling; Phase 2

Conditions: Non-Hodgkin Lymphoma

Treatments: Drug: Prednisone; Drug: Lenalidomide; Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: CC-99282; Drug: Doxorubicin Hydrochloride [HCl]; Drug: Venetoclax; Drug: Ibrutinib; Drug: Epcoritamab; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05283720

2021-005725-24 (EudraCT Number)

M22-132

Details and patient eligibility

About

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cell (a white blood cell responsible for fighting infections). The purpose of this study is to assess the safety and tolerability of epcoritamab in combination with anti-neoplastic agents in adult participants with Non-Hodgkin lymphoma (NHL). Adverse events and change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of NHL. Study doctors put the participants in groups called treatment arms. The combination of epcoritamab with anti-neoplastic agents will be explored. Each treatment arm receives a different treatment combination depending on eligibility. Approximately 394 adult participants with NHL will be enrolled in 100 sites globally.

In both the dose escalation and dose expansion arms participants will receive subcutaneous (SC) epcoritamab in 28-day or 21 day cycles dependent on the arm in combination with the anti-neoplastic agents described below:

1: Oral lenalidomide in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL); 2: Oral ibrutinib and oral lenalidomide in participants with with R/R DLBCL; 3: Intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in participants with newly diagnosed treatment-naïve DLBCL; 4: Oral CC-99282 in participants with R/R DLBCL; 5: Oral CC-99282 in participants with R/R follicular lymphoma (FL); 6A: Oral ibrutinib in participants with R/R mantle cell lymphoma (MCL); 6B: Oral ibrutinib, and oral venetoclax in participants with R/R MCL; 7: Oral ibrutinib, and oral venetoclax in participants with newly diagnosed treatment-naïve MCL.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Enrollment: 394 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of:

  -- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma (FL) or nodal marginal zone lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to World Health Organization (WHO) 2016 classification and documented in pathology report:

  • DLBCL, not otherwise specified (NOS).
  • High-grade B cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations per WHO 2016 ("double-hit" or "triple-hit") Note: High-grade B-cell lymphomas NOS or other double- /triple-hit lymphomas (with histologies not consistent with DLBCL) are not eligible.
  • Follicular lymphoma (FL) Grade 3B. OR

• FL with histologically confirmed CD20+ Grade 1 to 3a and no evidence of histologic transformation to an aggressive lymphoma at most recent representative tumor biopsy, according to WHO 2016 classification. OR

• Mantle cell lymphoma (MCL) with histologically confirmed CD20+ disease at most recent representative tumor biopsy according to the WHO 2016 classification with evidence of overexpression of cyclin D1 in association with relevant markers or evidence of t(11;14) assessed by flow cytometry, FISH, or polymerase chain reaction (PCR).

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, except for Arms 6 and 7 where ECOG performance status must be 0-1.

• Must have 1 or more measurable disease sites:

  • A positron emission tomography (PET) /computed tomography (CT) scan demonstrating PET-positive lesion(s) AND
  • At least 1 measurable nodal lesion (long axis > 1.5 cm) or >= 1 measurable extra-nodal lesion (long axis > 1.0 cm) on CT scan or magnetic resonance imaging (MRI).

Exclusion criteria

• Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20.
• Toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v 5.0), Grade 2 or below, with the exception of alopecia. Other eligibility criteria (e.g., laboratory, cardiac criteria) must also be met.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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394 participants in 15 patient groups

Arm 1: Dose Escalation

Experimental group

Description:

Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of subcutaneous (SC) epcoritamab in combination with oral lenalidomide in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Lenalidomide

Arm 2: Dose Escalation

Experimental group

Description:

Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Ibrutinib

Drug: Lenalidomide

Arm 3: Dose Escalation

Experimental group

Description:

Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.

Treatment:

Drug: Cyclophosphamide

Drug: Epcoritamab

Drug: Doxorubicin Hydrochloride [HCl]

Drug: Rituximab

Drug: Polatuzumab Vedotin

Drug: Prednisone

Arm 4: Dose Escalation

Experimental group

Description:

Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: CC-99282

Arm 5: Dose Escalation

Experimental group

Description:

Participants with R/R follicular lymphoma (FL) will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: CC-99282

Arm 6A: Dose Escalation

Experimental group

Description:

Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Ibrutinib

Arm 6B: Dose Escalation

Experimental group

Description:

Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Venetoclax

Drug: Ibrutinib

Arm 7: Dose Escalation

Experimental group

Description:

Participants with newly diagnosed treatment-naïve MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Treatment:

Drug: Epcoritamab

Arm 1: Dose Expansion

Experimental group

Description:

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral lenalidomide in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Lenalidomide

Arm 2: Dose Expansion

Experimental group

Description:

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Ibrutinib

Drug: Lenalidomide

Arm 3: Dose Expansion

Experimental group

Description:

Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.

Treatment:

Drug: Cyclophosphamide

Drug: Epcoritamab

Drug: Doxorubicin Hydrochloride [HCl]

Drug: Rituximab

Drug: Polatuzumab Vedotin

Drug: Prednisone

Arm 4: Dose Expansion

Experimental group

Description:

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Treatment:

Drug: Epcoritamab

Arm 5: Dose Expansion

Experimental group

Description:

Participants with R/R FL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Treatment:

Drug: Epcoritamab

Arm 6: Dose Expansion

Experimental group

Description:

Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.

Treatment:

Drug: Epcoritamab

Drug: Ibrutinib

Arm 7: Dose Expansion

Experimental group

Description:

Participants with newly diagnosed treatment-naïve MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Treatment:

Drug: Venetoclax

Drug: Ibrutinib