A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma

B-cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03677141
• Other study ID #: GO40515
• Secondary ID: 2018-001039-29
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 8, 2019
• Est. completion date: October 12, 2023

Study information

• Verified date: February 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 in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: October 12, 2023
• Est. primary completion date: October 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for Phase Ib and Phase II Portions

• 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

• Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2

• Adequate hematologic function

Inclusion Criteria for Phase Ib Portion

Participants must also meet the following criteria for study entry into the Phase Ib portion:

• Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen

• Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy

• Treatment with at least one prior CD20-directed therapy

• Group B only: no prior treatment with polatuzumab vedotin

Inclusion Criteria for Phase II Portion

Participants must also meet the following criteria for study entry in the Phase II portion:

• Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification

• International Prognostic Index (IPI) score of 2-5

Exclusion Criteria

• Prior treatment with mosunetuzumab

• Prior allogenic stem-cell transplant

• Current Grade >1 peripheral neuropathy

• Participants with 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)

• Prior solid organ transplantation

• History of autoimmune disease

• Current or past history of central nervous system (CNS) lymphoma

• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

• Significant cardiovascular disease or pulmonary disease

• Clinically significant history of liver disease

• Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis

Exclusion Criteria for Phase Ib Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:

• Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1

• Prior treatment with radiotherapy within 2 weeks prior to C1D1

• Adverse events from prior anti-cancer therapy resolved to =Grade 1 (with the exception of alopecia and anorexia)

• Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)

Exclusion Criteria for Phase II Portion

Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:

• Participants with transformed lymphoma

• Prior therapy for B-cell NHL

Related Conditions & MeSH terms

• B-cell Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
• Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV.
• Rituxumab
Participants will receive rituxumab via IV.
• Cyclophosphamide
Participants will receive cyclophosphamide via IV.
• Doxorubicin
Participants will receive doxorubicin via IV.
• Vincristine
Participants will receive vincristine via IV.
• Prednisone
Participants will receive oral prednisone.
• Tocilizumab
Participants will receive tocilizumab via IV.

Locations

Country	Name	City	State
Austria	Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU	Salzburg
Austria	LKH Steyr	Steyr
Austria	Hanusch-Krankenhaus	Wien
Austria	Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien	Wien
France	CHU Henri Mondor; Service d'Oncologie Medicale	Creteil
France	Centre Leon Berard	Lyon
France	Hôpital Saint-Louis	Paris
France	Centre Henri Becquerel- Centre de Lutte Contre le Cancer	Saint Herblain
France	Gustave Roussy	Villejuif
Korea, Republic of	Pusan National University Yangsan Hospital	Gyeongsangnam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Maria Sklodowska-Curie Memorial Cancer Centre	Gliwice
Poland	Ma?opolskie Centrum Medyczne	Kraków
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka	Slupsk
Poland	Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych	Warsaw
Poland	Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku	Wroc?aw
Spain	Institut Catala d?Oncologia Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital San Pedro de Alcantara; Servicio de Hematología	Caceres
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Banner MD Anderson Cancer Center	Greeley	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California; Moores Cancer Center	La Jolla	California
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica	Santa Monica	California
United States	Scott and White Hospital; Cancer Center	Temple	Texas
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Austria,  France,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AE)		Baseline through approximately 90 days after the last study treatment
Primary	Complete Response (CR) Rate at the Time of Primary Response Assessment Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Assessed According to Lugano 2014 Response Criteria		Approximately 6-8 weeks after Cycle 6 (cycle = 21 days), or at early treatment discontinuation
Secondary	Maximum Serum Concentration (Cmax) of Mosunetuzumab		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		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		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		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		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Maximum Plasma Concentration (Cmax) of Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Minimum Plasma Concentration (Cmin) of Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	AUC of Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	CL of Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Vss of Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Best Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at any Time on Study Based on PET-CT and/or CT scan as Assessed According to Lugano 2014 Response Criteria		Baseline through 2 years after partial response assessment (PRA) (up to a total of approximately 2.5 years)
Secondary	Duration of Response (DOR)		From the first occurrence of a response to disease progression, relapse, or death, whichever comes 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	ADAs to Polatuzumab Vedotin		At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary	Progression-Free Survival (PFS)		From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	PFS at 1 Year		Randomization to 1 Year
Secondary	Event-Free Survival (EFS)		From randomization to the first occurrence of disease progression or relapse, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary	Time to Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue		From baseline through follow-up (up to approximately 2.5 years)
Secondary	Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale		From baseline through follow-up (up to approximately 2.5 years)