A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: B-cell Non-Hodgkin Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Rituxumab; Drug: Polatuzumab Vedotin; Drug: Tocilizumab; Drug: Mosunetuzumab; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03677141

GO40515

2018-001039-29 (EudraCT Number)

Details and patient eligibility

About

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).

Enrollment: 117 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Phase Ib and Phase II Portions

• At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
• Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
• Adequate hematologic function

Inclusion Criteria for Phase Ib Portion

Participants must also meet the following criteria for study entry into the Phase Ib portion:

• Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
• Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
• Treatment with at least one prior CD20-directed therapy
• Group B only: no prior treatment with polatuzumab vedotin

Inclusion Criteria for Phase II Portion

Participants must also meet the following criteria for study entry in the Phase II portion:

• Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
• International Prognostic Index (IPI) score of 2-5

Exclusion Criteria

• Prior treatment with mosunetuzumab
• Prior allogenic stem-cell transplant
• Current Grade >1 peripheral neuropathy
• Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
• Prior solid organ transplantation
• History of autoimmune disease
• Current or past history of central nervous system (CNS) lymphoma
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Significant cardiovascular disease or pulmonary disease
• Clinically significant history of liver disease
• Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis

Exclusion Criteria for Phase Ib Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:

• Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
• Prior treatment with radiotherapy within 2 weeks prior to C1D1
• Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
• Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)

Exclusion Criteria for Phase II Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:

• Participants with transformed lymphoma
• Prior therapy for B-cell NHL

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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117 participants in 6 patient groups

Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding

Experimental group

Description:

Participants will receive M-CHOP up to the phase II recommended dose (RP2D).

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Doxorubicin

Drug: Tocilizumab

Drug: Mosunetuzumab

Drug: Polatuzumab Vedotin

Drug: Cyclophosphamide

Phase Ib: M-CHP-Pola Dose-Finding

Experimental group

Description:

Participants will receive M-CHP-Pola up to the RP2D.

Treatment:

Drug: Prednisone

Drug: Doxorubicin

Drug: Tocilizumab

Drug: Mosunetuzumab

Drug: Polatuzumab Vedotin

Drug: Cyclophosphamide

Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort

Experimental group

Description:

Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Doxorubicin

Drug: Tocilizumab

Drug: Mosunetuzumab

Drug: Cyclophosphamide

Phase II: M-CHP-Pola 1L DLBCL

Experimental group

Description:

Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.

Treatment:

Drug: Prednisone

Drug: Doxorubicin

Drug: Tocilizumab

Drug: Mosunetuzumab

Drug: Polatuzumab Vedotin

Drug: Cyclophosphamide

Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL

Active Comparator group

Description:

Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.

Treatment:

Drug: Prednisone

Drug: Doxorubicin

Drug: Rituxumab

Drug: Polatuzumab Vedotin

Drug: Cyclophosphamide

Phase II: M-CHOP 1L DLBCL

Experimental group

Description:

Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Doxorubicin

Drug: Tocilizumab

Drug: Mosunetuzumab

Drug: Cyclophosphamide