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NCT05091424PHASE1Recruiting

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

Hoffmann-La Roche

Start Date

3/7/2022

Completion Date

2/10/2032

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) or small lymphocytic lymphoma (SLL). 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 three 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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 up to three cycles of mosunetuzumab administration Inclusion Criteria Specific to Arm C: * Non-US participants only 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

Interventions

DRUG

Mosunetuzumab

DRUG

Tocilizumab

DRUG

Venetoclax

DRUG

Rituximab

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Conditions

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Locations

Mayo Clinic Rochester

Rochester, Minnesota 55902

United States

Memorial Sloan-Kettering Cancer Center

New York, New York 10065

United States

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio 43210

United States

Uni of Texas - Md Anderson Cancer Center

Houston, Texas 77030

United States

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah 84112

United States

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland 4102

Australia

Peter MacCallum Cancer Center

East Melbourne, Victoria 3002

Australia

Monash Medical Centre

Melbourne, Victoria 3168

Australia

Peking University People's Hospital

Beijing, 100044

China

Southern Medical University Nanfang Hospital

Guangzhou, 510515

China

The First Affiliated Hospital of Nanchang University

Nanchang,

China

Tianjin Institute of Hematology & Blood Diseases Hospital

Tianjin, 301600

China

Chu de Clermont Ferrand

Clermont-Ferrand, 63003

France

IUCT Oncopole

Toulouse, 31059

France

Universitätsklinikum Augsburg

Augsburg, 86156

Germany

Uniklinik Koln

Cologne, 50937

Germany

Universitätsklinikum Ulm

Ulm, 89081

Germany

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

Brescia, Lombardy 25123

Italy

Osp. San Raffaele

Milan, Lombardy 20132

Italy

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy 20162

Italy

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia

Sant'Andrea Delle Fratte (PG), Umbria 06132

Italy

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214

Poland

PRATIA MCM Kraków

Krakow, 30-727

Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, 50-367

Poland

Seoul National University Hospital

Seoul, 03080

South Korea

Seoul St Mary's Hospital

Seoul, 06591

South Korea

Yeouido St. Mary's Hospital

Seoul, 07345

South Korea

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Christie Hospital NHS Trust

Manchester, M20 4BX

United Kingdom

Churchill Hospital

Oxford, OX3 7LE

United Kingdom