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

NCT05091424 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BO43243
• Study Type: interventional
• Target: 137
• Locations: 10 countries
• Sites: 31

Brief Summary

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 (open to non-US participants only) 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.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Rate of Dose-Limiting Toxicities (DLTs)

  Up to approximately 12 months (Arms A and B) or 24 months (Arm C)

Secondary Outcomes (12)

• 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

• 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))

Study Arms (3)

Arm A

EXPERIMENTAL

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: Mosunetuzumab; Drug: Tocilizumab

Arm B

EXPERIMENTAL

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: Mosunetuzumab; Drug: Tocilizumab

Arm C (non-US participants only)

EXPERIMENTAL

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 (this arm is open only to participants outside of the US)

Drug: Mosunetuzumab; Drug: Tocilizumab; Drug: Venetoclax

Interventions

Mosunetuzumab DRUG

Participants will receive subcutaneous (SC) mosunetuzumab

Also known as: Lunsumio

Arm A; Arm B; Arm C (non-US participants only)

Tocilizumab DRUG

Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.

Arm A; Arm B; Arm C (non-US participants only)

Venetoclax DRUG

Participants will receive daily oral venetoclax

Also known as: Venclyxto, Venclexta

Arm C (non-US participants only)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Non-US participants only

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (31)

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

WITHDRAWN

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Uni of Texas - Md Anderson Cancer Center

Houston, Texas, 77030, United States

WITHDRAWN

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Peter MacCallum Cancer Center

East Melbourne, Victoria, 3002, Australia

COMPLETED

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

RECRUITING

Peking University People's Hospital

Beijing, 100044, China

RECRUITING

Southern Medical University Nanfang Hospital

Guangzhou, 510515, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, China

RECRUITING

Tianjin Institute of Hematology & Blood Diseases Hospital

Tianjin, 301600, China

RECRUITING

Chu de Clermont Ferrand

Clermont-Ferrand, 63003, France

WITHDRAWN

IUCT Oncopole

Toulouse, 31059, France

WITHDRAWN

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

RECRUITING

Uniklinik Koln

Cologne, 50937, Germany

WITHDRAWN

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, 25123, Italy

RECRUITING

Osp. San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

RECRUITING

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia

Sant'Andrea Delle Fratte (PG), Umbria, 06132, Italy

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

RECRUITING

PRATIA MCM Kraków

Krakow, 30-727, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, 50-367, Poland

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Seoul St Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Yeouido St. Mary's Hospital

Seoul, 07345, South Korea

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

tocilizumab; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BO43243 https://forpatients.roche.com/

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 25, 2021
• Study Start: March 7, 2022
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): February 28, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); US (5); DE (3); AU (3); KR (3); ES (2); CN (4); FR (2); PL (3); IT (4)