A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma

An Open-Label, Randomized, Multicenter, Phase Ib/II Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab; Drug: Rituximab; Drug: Mosunetuzumab (SC)

• Study Type: Interventional
• Enrollment (Estimated): 422
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Haine-Saint-Paul, Belgium, 7100
    • CH Jolimont - Lobbes (Jolimont)
  • Ottignies, Belgium, 1340
    • Clinique St Pierre asbl
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Caceres, Spain, 10003
    • Hospital de San Pedro de Alcantara
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor; Servicio de Hematologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Oncologia
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals NHS Trust; Pharmacy Dept
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham School of Medicine
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232-1301
      • University of Pittsburgh - Hillman Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Lifespan Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Froedtert Hospital;Nephrology Section

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• ECOG PS of 0, 1, or 2
• Histologically confirmed FL, DLBCL, or MCL
• Must have received at least one prior systemic treatment regimen containing an anti-CD20-directed therapy for DLBCL or FL
• For MCL, participants must have received at least two prior systemic treatment regiments, which include 1) anti-CD20-directed therapy, 2) BTK inhibitor, and 3) anthracycline or bendamustine
• Relapsed to prior regimen(s) after having a documented history of response (complete response [CR], CR unconfirmed [CRu], or partial response [PR]) of >/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy
• Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension
• Adequate hematologic, renal, and hepatic function

Key Exclusion Criteria:

• Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies
• Prior treatment with polatuzumab vedotin
• Current > Grade 1 peripheral neuropathy
• Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (ADC) within 4 weeks before first dose of study treatment
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
• Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
• Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration
• Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first study treatment administration
• Prior allogeneic SCT
• Prior solid organ transplantation
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Current or past history of central nervous system (CNS) lymphoma or CNS disease
• History of autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Finding; Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.	Drug: Mosunetuzumab (IV); Participants will receive intravenous (IV) mosunetuzumab.; Other Names: BTCT4465A; Drug: Polatuzumab vedotin; Participants will receive IV polatuzumab vedotin.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed.
Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL; Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.	Drug: Mosunetuzumab (IV); Participants will receive intravenous (IV) mosunetuzumab.; Other Names: BTCT4465A; Drug: Polatuzumab vedotin; Participants will receive IV polatuzumab vedotin.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed.
Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL; 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.	Drug: Mosunetuzumab (IV); Participants will receive intravenous (IV) mosunetuzumab.; Other Names: BTCT4465A; Drug: Polatuzumab vedotin; Participants will receive IV polatuzumab vedotin.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed.; Drug: Rituximab; Participants will receive IV rituximab.
Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL; Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.	Drug: Polatuzumab vedotin; Participants will receive IV polatuzumab vedotin.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed.; Drug: Mosunetuzumab (SC); Participants will receive subcutaneous (SC) mosunetuzumab.
Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL; 2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.	Drug: Polatuzumab vedotin; Participants will receive IV polatuzumab vedotin.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed.; Drug: Mosunetuzumab (SC); Participants will receive subcutaneous (SC) mosunetuzumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin	Cycle 1 to Cycle 2 (cycle length = 21 days)
Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin	Cycle 1 to Cycle 2 (cycle length = 21 days)
Percentage of Participants with Adverse Events (AE)	Baseline through approximately 90 days after last study treatment
Best Objective Response Rate (ORR), Defined as CR or Partial Response (PR) at any Time, Based on PET-CT and/or CT Scan, as Determined by the Independent Review Committee (IRC) using Standard Criteria for NHL	Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)

Secondary Outcome Measures

Outcome Measure	Time Frame
Best ORR (CR or PR at any Time) Based on PET-CT and/or CT Scan, as Determined by the Investigator Using Standard Criteria for NHL	Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Best CR Rate on Study Based on PET-CT, and/or CT Scan, as Determined by the Investigator and IRC Using Standard Criteria for NHL	Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
CR Rate at the Time of Primary Response Assessment (PRA) Based on PET-CT, as Determined by the Investigator and IRC Using Standard Criteria for NHL	Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
ORR, Defined as CR or PR, at PRA Based on PET-CT as Determined by the Investigator and IRC Using Standard Criteria for NHL	Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Duration of Response (DOR) as Determined by the Investigator and IRC Using Standard Criteria for NHL	From the first occurrence of a documented response to disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Progression-Free Survival (PFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL	From time of first study treatment to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Event-Free Survival (EFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL	From time of first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death from any cause, whichever occurs first (up to approximately 60 months)
Overall Survival (OS)	From time of first study treatment to death from any cause (up to approximately 60 months)
Anti-Drug Antibodies (ADAs) to Mosunetuzumab	At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
ADAs to Polatuzumab Vedotin	At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Mosunetuzumab Serum Concentration	At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2018
• Primary Completion (Actual): January 30, 2024
• Study Completion (Estimated): July 20, 2025

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 14, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Immunoconjugates; Rituximab; Polatuzumab vedotin
• Other Study ID Numbers: GO40516; 2018-001141-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No