A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study Details
Study Description
Brief Summary
This study will assess the safety, tolerability, pharmaokinetics, and preliminary efficacy of mosunetuzumab in participants with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: R/R CLL Participants will receive weekly step-up dosing of mosunetuzumab until the target dose is reached, after which mosunetuzumab will be administered once every 21 days for up to 17 cycles (cycle = 21 days) or until objective disease progression or unacceptable toxicity, whichever occurs first. |
Drug: Mosunetuzumab
Participants will receive subcutaneous (SC) mosunetuzumab for up to 17 cycles (cycle = 21 days).
Drug: Tocilizumab
Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.
|
Outcome Measures
Primary Outcome Measures
- Rate of Dose-Limiting Toxicities (DLTs) [Up to approximately 12 months]
Secondary Outcome Measures
- 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)]
- Overall Survival (OS) [From the first dose of study drug to death from any cause (up to approximately 12 months)]
- 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 (up to approximately 12 months)]
- Complete Response (CR) Rate [Up to 8-12 weeks after the last dose of study drug]
- 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)]
- Percentage of Participants with Adverse Events (AEs) [Up to approximately 12 months]
- Maximum Serum Concentration (Cmax) of Mosunetuzumab SC [Up to approximately 12 months]
- Minimum Serum Concentration (Cmin) of Mosunetuzumab SC [Up to approximately 12 months]
- Time to Maximum Concentration (Tmax) of Mosunetuzumab SC [Up to approximately 12 months]
Eligibility Criteria
Criteria
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
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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
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Adequate liver function unless directly attributable to the participant's CLL
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Life expectancy > 6 months
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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)
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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
Exclusion Criteria:
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Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable)
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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
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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; use of monoclonal antibodies or antibody-drug conjugates within 4 weeks prior to first 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 or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment; other prior cancer immunotherapy not explicitly defined by the protocol is to be discussed with the medical monitor to determine eligibility
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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
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Transformation of CLL to aggressive non-Hodgkin's lymphoma (NHL)
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History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
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Contraindication to tocilizumab
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History of prior malignancy except for conditions defined by the protocol
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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
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Evidence of any significant concomitant disease that could affect compliance with the protocol or interpretation of results
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan-Kettering Cancer Center; Hematology/Oncology | New York | New York | United States | 10065 |
| 2 | Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology | Woolloongabba | Queensland | Australia | 4102 |
| 3 | Monash Medical Centre; Haematology | Melbourne | Victoria | Australia | 3168 |
| 4 | Peter MacCallum Cancer Center | North Melbourne | Victoria | Australia | 3051 |
| 5 | CHU DE CLERMONT FERRAND; Service de Thérapie Cellulaire et d'Hématologie clinique adultes | Clermont-Ferrand | France | 63003 | |
| 6 | IUCT Oncopole; Hematologie | Toulouse | France | 31059 | |
| 7 | A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia | Brescia | Lombardia | Italy | 25123 |
| 8 | Osp. San Raffaele; Dip. Di Oncoematologia | Milano | Lombardia | Italy | 20132 |
| 9 | Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica | Sant'Andrea Delle Fratte (PG) | Umbria | Italy | 06132 |
| 10 | Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia | Barcelona | Spain | 08025 | |
| 11 | Hospital Universitari Vall d'Hebron; Servicio de Hematologia | Barcelona | Spain | 08035 | |
| 12 | Churchill Hospital; Department of Oncology | Oxford | United Kingdom | OX3 7LE |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BO43243