A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
- Conditions
- Lymphocytic Leukemia, ChronicLymphoma, Non Hodgkin
- Interventions
- Registration Number
- NCT02500407
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 713
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- B-cell hematologic malignancies expected to express the cluster of differentiation 20 (CD20) antigen who have relapsed after or failed to respond to at least one prior treatment regimen and for whom there is no available therapy expected to improve survival
- Adequate hepatic, hematologic, and renal function
Key
- Pregnant or lactating women
- Monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, chemotherapy, or other investigational anti-cancer agent within 4 weeks prior to study drug
- Treatment with radiotherapy within 2 weeks prior to the first BTCT4465A (Mosunetuzumab) administration
- Systemic immunosuppressive medication within 2 weeks prior to study drug
- Autologous stem cell transplantation (SCT) within 100 days prior to study drug, or any prior allogeneic SCT or solid organ transplantation
- Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia
- History of central nervous system (CNS) lymphoma or other CNS disease
- Significant cardiovascular or pulmonary disease
- Hepatitis B or C or human immunodeficiency virus (HIV)
- Receipt of a live attenuated vaccine within 4 weeks prior to study drug
- Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first BTCT4465A (Mosunetuzumab) administration
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation BTCT4465A (Mosunetuzumab) IV Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level. Dose Expansion BTCT4465A (Mosunetuzumab) IV Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab. Dose Escalation BTCT4465A (Mosunetuzumab) SC Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level. Dose Expansion BTCT4465A (Mosunetuzumab) SC Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab. Dose Escalation Atezolizumab Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level. Dose Expansion Atezolizumab Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
- Primary Outcome Measures
Name Time Method Atezolizumab Serum Concentration Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months) Percentage of Participants with Complete Response as Assessed Using Standard Criteria for NHL Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal) Maximum Tolerated Dose (MTD) of BTCT4465A (Mosunetuzumab) BTCT4465A (Mosunetuzumab) single agent: Cycle 1; BTCT4465A (Mosunetuzumab) in combination with atezolizumab: during the first cycle that BTCT4465A (Mosunetuzumab) and atezolizumab are administered concurrently (cycle length = 21 days) Percentage of Participants With Adverse Events Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 14 months) BTCT4465A (Mosunetuzumab) Serum Concentration Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) as Assessed Using Standard Criteria for NHL Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, withdrawal, or death from any cause) Overall Survival Baseline until death from any cause (up to approximately 4 years) Duration of Response as Assessed Using Standard Criteria for NHL Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal) European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Scores to Assess Health-Related Quality of Life (HRQoL) Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 4 years). The Functional Assessment of Cancer Therapy-Lymphoma (FACT-lym) Subscale, and the EuroQol 5 Dimension-5 Level (EQ-5D-5L) Questionnaire scores will also be used to assess HRQoL
Objective Response Rate (ORR) Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Trial Locations
- Locations (26)
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Sansum Medical Clinic, Inc.
🇺🇸Santa Barbara, California, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Cancer Center - Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center at Westchester
🇺🇸Harrison, New York, United States
New York Uni Medical Center
🇺🇸New York, New York, United States
Willamette Valley Cancer Insitute and Research Center
🇺🇸Springfield, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Icon Cancer Care South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Monash Health Clinical Trial Pharmacy department
🇦🇺Clayton, Victoria, Australia
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitatsklinikum Koln
🇩🇪Koln, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Germany
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Clínica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Vall d Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Barts Cancer Institute
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital;Institute of Cancer Research
🇬🇧Sutton, United Kingdom