A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia

A Phase IB Open-Label, Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

This study will assess the safety, tolerability, pharmaokinetics, and preliminary efficacy of mosunetuzumab (Lunsumio) monotherapy in participants with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). This study will also allow participants who are currently progressing on a Bruton tyrosine kinase inhibitor (BTKi) and requiring salvage therapy as assessed by the treating physician to continue their BTKi throughout the screening period and for the first two cycles of mosunetuzumab. An additional arm has been added to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with venetoclax, a B-cell lymphoma 2 (BCL2) inhibitor.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Tocilizumab; Drug: Mosunetuzumab; Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 137
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO43243 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre; Haematology
    • North Melbourne, Victoria, Australia, 3051
      • Recruiting
      • Peter Maccallum Cancer Center
• France
  • Clermont-Ferrand, France, 63003
    • Suspended
    • CHU DE CLERMONT FERRAND; Service de Thérapie Cellulaire et d'Hématologie clinique adultes
  • Toulouse, France, 31059
    • Recruiting
    • IUCT Oncopole; Hematologie
• Germany
  • Augsburg, Germany, 86156
    • Recruiting
    • Universitätsklinikum Augsburg; II. Med. Klinik
  • Köln, Germany, 50937
    • Recruiting
    • Uniklinik Koln; Klinik I fur Innere Medizin
  • Ulm, Germany, 89081
    • Recruiting
    • Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
• Italy
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Recruiting
      • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
    • Milano, Lombardia, Italy, 20132
      • Recruiting
      • Osp. San Raffaele; Dip. Di Oncoematologia
    • Milano, Lombardia, Italy, 20162
      • Completed
      • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
  • Umbria
    • Sant'Andrea Delle Fratte (PG), Umbria, Italy, 06132
      • Recruiting
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron; Servicio de Hematologia
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
• United Kingdom
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Churchill Hospital; Department of Oncology
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a diagnosis of CLL requiring treatment according to the International Workshop on CLL (iwCLL) criteria (Hallek et al 2018)
• Eastern Cooperative Oncology Group (ECOG) performance score (PS) of ≤ 2
• Adequate bone marrow (BM) function independent of growth factor or transfusion support, within 2 weeks of screening, at screening as defined by the protocol unless cytopenia is clearly due to marrow involvement of CLL
• Adequate liver function unless directly attributable to the participant's CLL
• Life expectancy > 6 months
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year, and agreement to refrain from donating eggs during the treatment period and for at least 3 months after the last dose of mosunetuzumab and 3 months after the last dose of tocilizumab (if applicable)
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm as defined by the protocol

Inclusion Criteria Specific to Arm B:

• Participants must have been taking a BTKi for at least 12 months, have demonstrated evidence of progressive disease while receiving the BTKi and require additional salvage therapy as assessed by their treating physician. Participants should be able to continue their previously prescribed BTKi at a stable dose throughout the study screening period and for the first two cycles of mosunetuzumab administration

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab and tocilizumab or within 30 days after the final dose of venetoclax (if applicable)
• Participants who have received any of the following treatments prior to study entry: treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies; allogenic stem cell transplant
• Participants who have received any of the following treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment: radiotherapy within 2 weeks prior to the first dose of study treatment; autologous stem cell transplant within 100 days prior to first study treatment; CAR T-cell therapy within 30 days before first study treatment; prior use of any monoclonal antibodies, radioimmunoconjugates, or antibody-drug conjugates for anti-CLL treatment within 4 weeks before first dose of study treatment; systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of study treatment; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy within 4 weeks prior to initiation of study treatment (except for participants enrolled in Arm B, where overlapping therapy is permitted; other prior cancer immunotherapy not explicitly defined by the protocol is to be discussed with the medical monitor to determine eligibility
• Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment, or in whom it is anticipated that such a vaccine will be required during the study period or within 5 months after the final dose of study treatment
• Transformation of CLL to aggressive non-Hodgkin's lymphoma (NHL)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Contraindication to tocilizumab
• History of prior malignancy except for conditions defined by the protocol
• Participants with infections requiring intravenous (IV) treatment with antibiotics or hospitalization within the last 4 weeks prior to enrollment or known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
• Evidence of any significant concomitant disease that could affect compliance with the protocol or interpretation of results
• Recent major surgery within 4 weeks prior to first study treatment administration, with the exception of protocol-mandated procedures (e.g., tumor biopsies and bone marrow biopsies)
• Positive SARS-CoV-2 test within 7 days prior to enrollment

Exclusion Criteria Specific to Arm C:

• Have received venetoclax therapy within 12 months prior to first study treatment administration
• Participants with known infection with HIV or human T-cell leukemia virus 1 (HTLV1)
• HIV testing will be performed in countries where mandatory testing by health authorities is required
• HTLV testing is required in participants from endemic countries
• Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• Participants who have received the following: strong and moderate CYP3A inhibitors within 7 days prior to the initiation of study treatment; strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment; steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration
• Have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration
• Inability to swallow a large number of tablets
• Malabsorption syndrome or other condition that precludes enteral route of administration
• Known allergy to both xanthine oxidase inhibitors and rasburicase

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy	Drug: Tocilizumab; Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.; Drug: Mosunetuzumab; Participants will receive subcutaneous (SC) mosunetuzumab; Other Names: Lunsumio
Experimental: Arm B; Participants with R/R CLL who have failed two prior lines of therapy, who are currently progressing on BTKi therapy, and who require salvage therapy as assessed by their treating physician will receive mosunetuzumab SC with BTKi overlap therapy for the first two cycles of mosunetuzumab SC	Drug: Tocilizumab; Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.; Drug: Mosunetuzumab; Participants will receive subcutaneous (SC) mosunetuzumab; Other Names: Lunsumio
Experimental: Arm C; Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax	Drug: Tocilizumab; Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.; Drug: Mosunetuzumab; Participants will receive subcutaneous (SC) mosunetuzumab; Other Names: Lunsumio; Drug: Venetoclax; Participants will receive daily oral venetoclax; Other Names: Venclexta; Venclyxto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Dose-Limiting Toxicities (DLTs)	Up to approximately 12 months (Arms A and B) or 24 months (Arm C)

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Up to 8-12 weeks after the last dose of study drug
Minimal Residual Disease (MRD) Response Rate	Up to 8-12 weeks after the last dose of study drug
Complete Response (CR) Rate	Up to 8-12 weeks after the last dose of study drug
Progression-Free Survival (PFS)	From the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Overall Survival (OS)	From the first dose of study drug to death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Event-Free Survival (EFS)	Between the date of the first study treatment to the date of disease progression/relapse, death, or start of new anti-leukemic therapy, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Duration of Response (DOR)	From the first occurrence of a documented objective response to disease progression by iwCLL 2018 criteria or death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Percentage of Participants with Adverse Events (AEs)	Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Maximum Serum Concentration (Cmax) of Mosunetuzumab SC	Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Minimum Serum Concentration (Cmin) of Mosunetuzumab SC	Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Time to Maximum Concentration (Tmax) of Mosunetuzumab SC	Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Incidence of Anti-Drug Antibodies (ADAs)	Baseline through end of study (up to approximately 12 months for Arms A and B, or 24 months for Arm C)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2022
• Primary Completion (Estimated): May 27, 2027
• Study Completion (Estimated): October 8, 2029

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: BO43243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

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