Description:
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).
Title
- Brief Title: 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
- Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
GO40515
- SECONDARY ID:
2018-001039-29
- NCT ID:
NCT03677141
Conditions
- B-cell Non-Hodgkin Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Mosunetuzumab | | Phase II: M-CHOP 1L DLBCL |
Polatuzumab Vedotin | | Phase II: M-CHP-Pola 1L DLBCL |
Rituxumab | | Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL |
Cyclophosphamide | | Phase II: M-CHOP 1L DLBCL |
Doxorubicin | | Phase II: M-CHOP 1L DLBCL |
Vincristine | | Phase II: M-CHOP 1L DLBCL |
Prednisone | | Phase II: M-CHOP 1L DLBCL |
Tocilizumab | | Phase II: M-CHOP 1L DLBCL |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding | Experimental | Participants will receive M-CHOP up to the phase II recommended dose (RP2D). | - Mosunetuzumab
- Polatuzumab Vedotin
- Cyclophosphamide
- Doxorubicin
- Vincristine
- Prednisone
- Tocilizumab
|
Phase Ib: M-CHP-Pola Dose-Finding | Experimental | Participants will receive M-CHP-Pola up to the RP2D. | - Mosunetuzumab
- Polatuzumab Vedotin
- Cyclophosphamide
- Doxorubicin
- Prednisone
- Tocilizumab
|
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort | Experimental | Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. | - Mosunetuzumab
- Cyclophosphamide
- Doxorubicin
- Vincristine
- Prednisone
- Tocilizumab
|
Phase II: M-CHP-Pola 1L DLBCL | Experimental | Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. | - Mosunetuzumab
- Polatuzumab Vedotin
- Cyclophosphamide
- Doxorubicin
- Prednisone
- Tocilizumab
|
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL | Active Comparator | Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. | - Polatuzumab Vedotin
- Rituxumab
- Cyclophosphamide
- Doxorubicin
- Prednisone
|
Phase II: M-CHOP 1L DLBCL | Experimental | Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. | - Mosunetuzumab
- Cyclophosphamide
- Doxorubicin
- Vincristine
- Prednisone
- Tocilizumab
|
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of Participants with Adverse Events (AE) |
Time Frame: | Baseline through approximately 90 days after the last study treatment |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Maximum Serum Concentration (Cmax) of Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Minimum Serum Concentration (Cmin) of Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Area Under the Curve (AUC) of Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Clearance (CL) of Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Volume of Distribution at Steady State (Vss) of Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Maximum Plasma Concentration (Cmax) of Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Minimum Plasma Concentration (Cmin) of Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | AUC of Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | CL of Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Vss of Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Best Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at any Time on Study Based on PET-CT and/or CT scan as Assessed According to Lugano 2014 Response Criteria |
Time Frame: | Baseline through 2 years after partial response assessment (PRA) (up to a total of approximately 2.5 years) |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DOR) |
Time Frame: | From the first occurrence of a response to disease progression, relapse, or death, whichever comes first (up to approximately 2.5 years) |
Safety Issue: | |
Description: | |
Measure: | Anti-Drug Antibodies (ADAs) to Mosunetuzumab |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | ADAs to Polatuzumab Vedotin |
Time Frame: | At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
Safety Issue: | |
Description: | |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years) |
Safety Issue: | |
Description: | |
Measure: | PFS at 1 Year |
Time Frame: | Randomization to 1 Year |
Safety Issue: | |
Description: | |
Measure: | Event-Free Survival (EFS) |
Time Frame: | From randomization to the first occurrence of disease progression or relapse, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first (up to approximately 2.5 years) |
Safety Issue: | |
Description: | |
Measure: | Time to Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue |
Time Frame: | From baseline through follow-up (up to approximately 2.5 years) |
Safety Issue: | |
Description: | |
Measure: | Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale |
Time Frame: | From baseline through follow-up (up to approximately 2.5 years) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
July 2, 2021