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
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.
Arms & interventions
- DrugMosunetuzumab
Participants will receive subcutaneous (SC) mosunetuzumab
- DrugTocilizumab
Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.
- DrugVenetoclax
Participants will receive daily oral venetoclax
Outcome measures
Primary
Rate of Dose-Limiting Toxicities (DLTs)
Time frame: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary
Objective Response Rate (ORR)
Time frame: Up to 8-12 weeks after the last dose of study drug
Minimal Residual Disease (MRD) Response Rate
Time frame: Up to 8-12 weeks after the last dose of study drug
Progression-Free Survival (PFS)
Time frame: 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)
Time frame: 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)
Time frame: 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))
Complete Response (CR) Rate
Time frame: Up to 8-12 weeks after the last dose of study drug
Duration of Response (DOR)
Time frame: 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)
Time frame: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Maximum Serum Concentration (Cmax) of Mosunetuzumab SC
Time frame: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Minimum Serum Concentration (Cmin) of Mosunetuzumab SC
Time frame: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Time to Maximum Concentration (Tmax) of Mosunetuzumab SC
Time frame: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Incidence of Anti-Drug Antibodies (ADAs)
Time frame: Baseline through end of study (up to approximately 12 months for Arms A and B, or 24 months for Arm C)
Eligibility criteria
Study locations (5)
Mayo Clinic Rochester
Rochester, Minnesota, 55902
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
Uni of Texas - Md Anderson Cancer Center
Houston, Texas, 77030
Huntsman Cancer Institute at The University of Utah
Salt Lake City, Utah, 84112