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)
An Open-Label, Multicenter, Phase I/II Trial Evaluating the Safety, Efficacy, and Pharmacokinetics of Escalating Doses of Mosunetuzumab (BTCT4465A) as a Single Agent and Combined With Atezolizumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia
1 other identifier
interventional
713
7 countries
35
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2015
Longer than P75 for phase_1
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 14, 2015
CompletedFirst Posted
Study publicly available on registry
July 16, 2015
CompletedStudy Start
First participant enrolled
September 15, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 21, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2025
CompletedSeptember 12, 2025
September 1, 2025
8.7 years
July 14, 2015
September 9, 2025
Conditions
Outcome Measures
Primary Outcomes (5)
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)
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)
Secondary Outcomes (5)
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)
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)
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).
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)
Study Arms (2)
Dose Escalation
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
Interventions
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via IV infusion.
Participants assigned to an atezolizumab combination group will receive atezolizumab 1200 mg administered as an IV infusion in combination with BTCT4465A (Mosunetuzumab).
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (35)
University of California San Diego Moores Cancer Center
La Jolla, California, 92093-0698, United States
Sansum Medical Clinic, Inc.
Santa Barbara, California, 93105, United States
Rocky Mountain Cancer Center
Denver, Colorado, 80218, United States
Yale University School Of Medicine
New Haven, Connecticut, 06510, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Cancer Center - Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Cancer Center at Westchester
Harrison, New York, 10604, United States
New York Uni Medical Center
New York, New York, 10016, United States
Willamette Valley Cancer Insitute and Research Center
Springfield, Oregon, 97477, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19103, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010, Australia
Icon Cancer Care South Brisbane
South Brisbane, Queensland, 4101, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
St. Vincent's Hospital Melbourne
Fitzroy, South Australia, 3065, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Monash Health Clinical Trial Pharmacy department
Clayton, Victoria, 3168, Australia
The Perth Blood Institute
Nedlands, Western Australia, 6009, Australia
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Universitatsklinikum Koln
Cologne, 50931, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, 55101, Germany
Klinikum der Universität München, Campus Großhadern
München, 83177, Germany
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Clínica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Universitario Vall d Hebron
Barcelona, 08035, Spain
Hospital Universitario La Paz
Madrid, 280146, Spain
Complejo Asistencial Universitario de Salamanca
Salamanca, 37007, Spain
Barts Cancer Institute
London, EC1A 7BE, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Royal Marsden Hospital;Institute of Cancer Research
Sutton, SM2 5PT, United Kingdom
Related Publications (14)
Danilov AV, Kambhampati Thiruvengadam S, Linton K, Cumings K, Chirikov V, Mutebi A, Bains Chawla S, Chhibber A, Rivas Navarro F, Marques Goncalves F, Wang A, Ding Z, Alshreef A, Favaro E, Hoehn D, Sureda A. Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma. Blood Adv. 2025 Aug 12;9(15):3754-3765. doi: 10.1182/bloodadvances.2024015274.
PMID: 40472301DERIVEDLi J, Liao MZ, Wilkins J, Penuel E, Wang B, Vadhavkar S, Peng K, Cao J, Li Z, Zhang Y, Li W, Li D, Zhou M, Wei MC, Kwan A, Zhao R, Li C, Li CC, Turner DC. Ethnic Sensitivity Assessment of Mosunetuzumab Pharmacokinetics and Pharmacodynamics in Chinese Patients With Relapsed or Refractory Follicular Lymphoma. Clin Transl Sci. 2025 May;18(5):e70211. doi: 10.1111/cts.70211.
PMID: 40279333DERIVEDChong EA, Penuel E, Napier EB, Lundberg RK, Budde LE, Shadman M, Matasar MJ, Bartlett NL, Flinn IW, Bosch F, Fay K, Goy A, Kumar A, Nastoupil LJ, Wei MC, Wu M, Yin S, Fraietta JA, Chong ER, Schuster SJ. Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas. Blood Adv. 2025 Feb 25;9(4):696-703. doi: 10.1182/bloodadvances.2024013640.
PMID: 39571171DERIVEDSehn LH, Bartlett NL, Matasar MJ, Schuster SJ, Assouline SE, Giri P, Kuruvilla J, Shadman M, Cheah CY, Dietrich S, Fay K, Ku M, Nastoupil LJ, Wei MC, Yin S, To I, Kaufman D, Kwan A, Penuel E, Bolen CR, Budde LE. Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after >/=2 prior therapies. Blood. 2025 Feb 13;145(7):708-719. doi: 10.1182/blood.2024025454.
PMID: 39447094DERIVEDRay MD, Kanters S, Beygi S, Best T, Wulff J, Limbrick-Oldfield E, Patel AR, Oluwole OO. Matching-Adjusted Indirect Comparisons of Axicabtagene Ciloleucel to Mosunetuzumab for the Treatment of Relapsed/Refractory Follicular Lymphoma. Transplant Cell Ther. 2024 Sep;30(9):885.e1-885.e11. doi: 10.1016/j.jtct.2024.06.016. Epub 2024 Jun 19.
PMID: 38901633DERIVEDJemaa S, Ounadjela S, Wang X, El-Galaly TC, Kostakoglu L, Knapp A, Ku G, Musick L, Sahin D, Wei MC, Yin S, Bengtsson T, De Crespigny A, Carano RAD. Automated Lugano Metabolic Response Assessment in 18F-Fluorodeoxyglucose-Avid Non-Hodgkin Lymphoma With Deep Learning on 18F-Fluorodeoxyglucose-Positron Emission Tomography. J Clin Oncol. 2024 Sep 1;42(25):2966-2977. doi: 10.1200/JCO.23.01978. Epub 2024 Jun 6.
PMID: 38843483DERIVEDBender B, Li CC, Marchand M, Turner DC, Li F, Vadhavkar S, Wang B, Deng R, Lu J, Jin J, Li C, Yin S, Wei M, Chanu P. Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Transl Sci. 2024 Jun;17(6):e13825. doi: 10.1111/cts.13825.
PMID: 38808543DERIVEDBudde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, Cheah CY, Ma CY, Huang H, Kwan A, Wei MC, Yin S, Bartlett NL. Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study. J Clin Oncol. 2024 Jul 1;42(19):2250-2256. doi: 10.1200/JCO.23.02329. Epub 2024 Mar 28.
PMID: 38547425DERIVEDSchuster SJ, Huw LY, Bolen CR, Maximov V, Polson AG, Hatzi K, Lasater EA, Assouline SE, Bartlett NL, Budde LE, Matasar MJ, Koeppen H, Piccione EC, Wilson D, Wei MC, Yin S, Penuel E. Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas. Blood. 2024 Feb 29;143(9):822-832. doi: 10.1182/blood.2023022348.
PMID: 38048694DERIVEDBosch F, Kuruvilla J, Vassilakopoulos TP, Maio DD, Wei MC, Zumofen MB, Nastoupil LJ. Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.
PMID: 37981564DERIVEDSanchez Alvarez J, Jaber M, Blanchet Zumofen MH. Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma. Oncol Ther. 2023 Dec;11(4):495-511. doi: 10.1007/s40487-023-00245-4. Epub 2023 Oct 18.
PMID: 37851321DERIVEDBartlett NL, Assouline S, Giri P, Schuster SJ, Cheah CY, Matasar M, Gregory GP, Yoon DH, Shadman M, Fay K, Yoon SS, Panizo C, Flinn I, Johnston A, Bosch F, Sehn LH, Wei MC, Yin S, To I, Li CC, Huang H, Kwan A, Penuel E, Budde LE. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2023 Sep 12;7(17):4926-4935. doi: 10.1182/bloodadvances.2022009260.
PMID: 37067952DERIVEDBudde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K, Ku M, Nastoupil L, Cheah CY, Wei MC, Yin S, Li CC, Huang H, Kwan A, Penuel E, Bartlett NL. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022 Aug;23(8):1055-1065. doi: 10.1016/S1470-2045(22)00335-7. Epub 2022 Jul 5.
PMID: 35803286DERIVEDBudde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, O'Hear C, Huang H, Kwan A, Li CC, Piccione EC, Wei MC, Yin S, Bartlett NL. Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. J Clin Oncol. 2022 Feb 10;40(5):481-491. doi: 10.1200/JCO.21.00931. Epub 2021 Dec 16.
PMID: 34914545DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 14, 2015
First Posted
July 16, 2015
Study Start
September 15, 2015
Primary Completion
May 21, 2024
Study Completion
September 1, 2025
Last Updated
September 12, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing.