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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05091424
• Other study ID #: BO43243
• Status: Recruiting
• Phase: Phase 1
• Start date: March 7, 2022
• Est. completion date: October 8, 2029

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO43243 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 137
• Est. completion date: October 8, 2029
• Est. primary completion date: May 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Mosunetuzumab
Participants will receive subcutaneous (SC) mosunetuzumab
• Tocilizumab
Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.
• Venetoclax
Participants will receive daily oral venetoclax

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Dose-Limiting Toxicities (DLTs)		Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary	Objective Response Rate (ORR)		Up to 8-12 weeks after the last dose of study drug
Secondary	Minimal Residual Disease (MRD) Response Rate		Up to 8-12 weeks after the last dose of study drug
Secondary	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))
Secondary	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))
Secondary	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))
Secondary	Complete Response (CR) Rate		Up to 8-12 weeks after the last dose of study drug
Secondary	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))
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary	Maximum Serum Concentration (Cmax) of Mosunetuzumab SC		Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary	Minimum Serum Concentration (Cmin) of Mosunetuzumab SC		Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary	Time to Maximum Concentration (Tmax) of Mosunetuzumab SC		Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary	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)