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

• ClinicalTrials.gov Identifier: NCT03677141
• Recruitment Status: Active, not recruiting
• First Posted: September 19, 2018
• Last Update Posted: May 16, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 11, 2018
• First Posted Date: September 19, 2018
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: February 8, 2019
• Actual Primary Completion Date: November 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2018)

• Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after the last study treatment ]
• Complete Response (CR) Rate at the Time of Primary Response Assessment Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Assessed According to Lugano 2014 Response Criteria [ Time Frame: Approximately 6-8 weeks after Cycle 6 (cycle = 21 days), or at early treatment discontinuation ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2018)

• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• PFS at 1 Year [ Time Frame: Randomization to 1 Year ]
• 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) ]
• 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) ]
• 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) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Non-Hodgkin Lymphoma

Intervention

• Drug: Mosunetuzumab
  Participants will receive intravenous (IV) mosunetuzumab.
• Drug: Polatuzumab Vedotin
  Participants will receive polatuzumab vedotin via IV.
• Drug: Rituxumab
  Participants will receive rituxumab via IV.
• Drug: Cyclophosphamide
  Participants will receive cyclophosphamide via IV.
• Drug: Doxorubicin
  Participants will receive doxorubicin via IV.
• Drug: Vincristine
  Participants will receive vincristine via IV.
• Drug: Prednisone
  Participants will receive oral prednisone.
• Drug: Tocilizumab
  Participants will receive tocilizumab via IV.

Study Arms

• Experimental: Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
  Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
  Interventions:

  • Drug: Mosunetuzumab
  • Drug: Polatuzumab Vedotin
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Tocilizumab
• Experimental: Phase Ib: M-CHP-Pola Dose-Finding
  Participants will receive M-CHP-Pola up to the RP2D.
  Interventions:

  • Drug: Mosunetuzumab
  • Drug: Polatuzumab Vedotin
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Prednisone
  • Drug: Tocilizumab
• Experimental: Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
  Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
  Interventions:

  • Drug: Mosunetuzumab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Tocilizumab
• Experimental: Phase II: M-CHP-Pola 1L DLBCL
  Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
  Interventions:

  • Drug: Mosunetuzumab
  • Drug: Polatuzumab Vedotin
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Prednisone
  • Drug: Tocilizumab
• Active Comparator: Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
  Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
  Interventions:

  • Drug: Polatuzumab Vedotin
  • Drug: Rituxumab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Prednisone
• Experimental: Phase II: M-CHOP 1L DLBCL
  Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.
  Interventions:

  • Drug: Mosunetuzumab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Tocilizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 17, 2018): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2023
• Actual Primary Completion Date: November 18, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Korea, Republic of, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03677141
• Other Study ID Numbers: GO40515; 2018-001039-29 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023