Clinical trial NCT02500407: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lymphocytic Leukemia, Chronic
Lymphoma, Non Hodgkin
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-16
Enrollment: 713
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of BTCT4465A (Mosunetuzumab)
timeFrame: 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)
measure: Percentage of Participants With Adverse Events
timeFrame: Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 14 months)
measure: BTCT4465A (Mosunetuzumab) Serum Concentration
timeFrame: Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
measure: Atezolizumab Serum Concentration
timeFrame: Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
measure: Percentage of Participants with Complete Response as Assessed Using Standard Criteria for NHL
timeFrame: 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:
measure: Duration of Response as Assessed Using Standard Criteria for NHL
timeFrame: 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)
measure: Progression-Free Survival (PFS) as Assessed Using Standard Criteria for NHL
timeFrame: 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)
measure: Overall Survival
timeFrame: Baseline until death from any cause (up to approximately 4 years)
measure: 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)
timeFrame: Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 4 years).
measure: Objective Response Rate (ORR)
timeFrame: 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)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Medical Clinic, Inc.
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center - Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: New York
country: United States
facility: New York Uni Medical Center
state: New York
city: Springfield
country: United States
facility: Willamette Valley Cancer Insitute and Research Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health Clinical Trial Pharmacy department
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Koln
country: Germany
facility: Universitatsklinikum Koln
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: London
country: United Kingdom
facility: Barts Cancer Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital;Institute of Cancer Research
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Budde 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.
citation: Budde 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.