Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Participants With Previously Untreated Diffuse Large B-Cell Lymphoma

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03677154
• Other study ID #: GO40554
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 23, 2019
• Est. completion date: August 3, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 188
• Est. completion date: August 3, 2025
• Est. primary completion date: August 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for All Cohorts

• At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
• Adequate hematologic function
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG >/= 2 will not be eligible Inclusion Criteria Specific to Cohort A

Participants in Cohort A must also meet the following criteria for study entry:

• Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen
• One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL
• Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria Inclusion Criteria Specific to Cohorts B and C

Participants in Cohorts B and C must also meet the following criteria for study entry:

• Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification
• Age >/= 80 years, or
• Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
• Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to </= 2 prior to enrollment Exclusion Criteria for All Cohorts

Participants who meet any of the following criteria will be excluded from study entry:

• Transformed lymphoma
• CNS lymphoma
• Prior treatment with mosunetuzumab
• Prior stem cell transplant (autologous and allogeneic)
• History of confirmed progressive multifocal leukoencephalopathy (PML)
• Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1
• Prior solid organ transplantation
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Clinically significant history of liver disease
• Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1)
• Significant cardiovascular disease Exclusion Criteria Specific to Cohort A

Participants in Cohort A who meet the following criteria will be excluded from study entry:

• Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to C1D1 Exclusion Criterion Specific to Cohorts B and C Participants in Cohorts B and C who meet the following criterion will be excluded from

study entry:

• Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy Exclusion Criteria Specific to Cohort C

Participants in Cohort C who meet the following criteria will be excluded from study entry:

• Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Mosunetuzumab Intravenous (IV)
Participants in cohorts A and B will receive IV mosunetuzumab.
• Mosunetuzumab Subcutaneous (SC)
Participants in Cohort C will receive SC mosunetuzumab.
• Polatuzumab Vedotin
Participants in Cohort C will receive IV polatuzumab vedotin.
• Tocilizumab
Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Locations

Country	Name	City	State
Israel	Soroka Medical Center	Beer Sheva
Israel	Carmel medical center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Ein-Karem; Clinical Pharmacology Unit	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar- Saba
Israel	Laniado Hospital-Sanz Medical Center	Netanya
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center; Pharmacy	Tel Aviv
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea Yeouido St. Mary's Hospital; Hematology-Oncology	Seoul
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp. z o. o.	Gdynia
Poland	PRATIA MCM Kraków	Kraków
Poland	Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli	Lublin
Poland	Szpital Wojewodzki w Opolu;Pododdz. Gastroenter., Pododdz. Hematologii	Opole
Poland	Instytut Hematologii i Transfuzjologii; Klinika Hematologii	Warszawa
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	Hospital San Pedro de Alcantara; Servicio de Hematología	Caceres
Spain	Institut Catala d Oncologia Hospitalet	Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Taiwan	Taipei Medical University ?Shuang Ho Hospital	New Taipei City
Taiwan	Chi-Mei Hospital, Liouying	Tainan
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama
United States	Rush University Medical Center; Rush University Cancer Center	Chicago	Illinois
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Fort Wayne Medical Institute	Fort Wayne	Indiana
United States	Norton Medical Plaza II; Norton Cancer Institute	Louisville	Kentucky
United States	Miami Cancer Institute of Baptist Health, Inc.	Miami	Florida
United States	University of Miami Sylvester Comprehensive Center	Miami	Florida
United States	Sloan Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica	Santa Monica	California
United States	Moffitt Cancer Center Screening and Prevention	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Israel,  Korea, Republic of,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events		Baseline through approximately 90 days after last study treatment
Primary	Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria (Cohort A)		6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
Primary	PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B)		6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
Primary	PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C)		6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
Secondary	Maximum Serum Concentration (Cmax) of Mosunetuzumab IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Mosunetuzumab IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Area Under the Curve (AUC) of Mosunetuzumab IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Clearance (CL) of Mosunetuzumab IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Maximum Serum Concentration (Cmax) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Area Under the Curve (AUC) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Clearance (CL) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Volume of Distribution at Steady State (Vss) of Mosunetuzumab SC		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Area Under the Curve (AUC) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Clearance (CL) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Volume of Distribution at Steady State (Vss) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Trough Concentration (Ctrough) of Polatuzumab Vedotin IV		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C)		6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
Secondary	Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (Cohorts A and C)		Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
Secondary	Best ORR (CR or PR at any time) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)		Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
Secondary	Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)		From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Secondary	Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)		From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)		From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Secondary	Overall Survival (OS)		From the first study treatment to death from any cause
Secondary	Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C)		From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C)		From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C)		From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C)		From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C)		From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Anti-Drug Antibodies (ADAs) to Mosunetuzumab		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C)		At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)