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)

Lymphocytic Leukemia, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02500407
• Other study ID #: GO29781
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 15, 2015
• Est. completion date: November 15, 2025

Study information

• Verified date: May 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 836
• Est. completion date: November 15, 2025
• Est. primary completion date: November 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphocytic Leukemia, Chronic
• Lymphoma
• Lymphoma, Non Hodgkin
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• BTCT4465A (Mosunetuzumab) IV
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via IV infusion.
• Atezolizumab
Participants assigned to an atezolizumab combination group will receive atezolizumab 1200 mg administered as an IV infusion in combination with BTCT4465A (Mosunetuzumab).
• BTCT4465A (Mosunetuzumab) SC
Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia
Australia	Monash Health Clinical Trial Pharmacy department	Clayton	Victoria
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	St. Vincent's Hospital Melbourne	Fitzroy	South Australia
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	The Alfred	Melbourne	Victoria
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Australia	The Perth Blood Institute	Nedlands	Western Australia
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	Wollongong Hospital; Cancer Care Centre	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Jewish General Hospital; Research Unit	Montréal	Quebec
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
Canada	BC Cancer Agency Vancouver Centre - PARENT	Vancouver	British Columbia
Germany	DIAKO Ev. Diakonie-Krankenhaus Bremen GmbH; Med. Klinik II; Hämatologie und internistische Onkologie	Bremen
Germany	St. Johannes Hospital; Abt. für Hämatologie und Onkologie	Dortmund
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Koln; Apotheke Uniklinik Koln	Koln
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III	München
Germany	Universitatsklinikum Munster	Münster
Germany	Universitätsklinikum Würzburg	Würzburg
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Complejo Asistencial Universitario de Salamanca	Salamanca
United Kingdom	Barts Cancer Institute	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital; Institute of Cancer Research; Pharmacy Stores	Sutton
United States	Memorial Sloan Kettering Cancer Center - Commack	Commack	New York
United States	Memorial Sloan-Kettering Cancer Center	Commack	New York
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	New York Uni Medical Center	New York	New York
United States	University of Pennsylvania; School of Medicine	Philadelphia	Pennsylvania
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	Sansum Medical Clinic, Inc.	Santa Barbara	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Willamette Valley Cancer Insitute and Research Center	Springfield	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	BTCT4465A (Mosunetuzumab) Serum Concentration		Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
Primary	Atezolizumab Serum Concentration		Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
Primary	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	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)
Secondary	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)
Secondary	Overall Survival		Baseline until death from any cause (up to approximately 4 years)
Secondary	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)	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	Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 4 years).
Secondary	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)