A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma

B-cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

An Open-Label, Randomized, Multicenter, Phase Ib/II Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03671018
• Other study ID #: GO40516
• Secondary ID: 2018-001141-13
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 25, 2018
• Est. completion date: July 20, 2025

Study information

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

Clinical Trial Summary

This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 422
• Est. completion date: July 20, 2025
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• ECOG PS of 0, 1, or 2
• Histologically confirmed FL, DLBCL, or MCL
• Must have received at least one prior systemic treatment regimen containing an anti-CD20-directed therapy for DLBCL or FL
• For MCL, participants must have received at least two prior systemic treatment regiments, which include 1) anti-CD20-directed therapy, 2) BTK inhibitor, and 3) anthracycline or bendamustine
• Relapsed to prior regimen(s) after having a documented history of response (complete response [CR], CR unconfirmed [CRu], or partial response [PR]) of >/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy
• Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension
• Adequate hematologic, renal, and hepatic function

Key Exclusion Criteria:

• Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies
• Prior treatment with polatuzumab vedotin
• Current > Grade 1 peripheral neuropathy
• Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (ADC) within 4 weeks before first dose of study treatment
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
• Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
• Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration
• Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first study treatment administration
• Prior allogeneic SCT
• Prior solid organ transplantation
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Current or past history of central nervous system (CNS) lymphoma or CNS disease
• History of autoimmune disease

Related Conditions & MeSH terms

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

Intervention

Drug:
• Mosunetuzumab (IV)
Participants will receive intravenous (IV) mosunetuzumab.
• Mosunetuzumab (SC)
Participants will receive subcutaneous (SC) mosunetuzumab.
• Polatuzumab vedotin
Participants will receive IV polatuzumab vedotin.
• Tocilizumab
Participants will receive IV tocilizumab as needed.
• Rituximab
Participants will receive IV rituximab.

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussel
Belgium	CH Jolimont - Lobbes (Jolimont)	Haine-Saint-Paul
Belgium	Clinique St Pierre asbl	Ottignies
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)	Saskatoon	Saskatchewan
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Hospital de San Pedro de Alcantara	Caceres
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Infanta Leonor; Servicio de Hematologia	Madrid
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Plymouth Hospitals NHS Trust; Pharmacy Dept	Plymouth
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Medical College of Wisconsin, Froedtert Hospital;Nephrology Section	Milwaukee	Wisconsin
United States	New York University Langone Medical Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Lifespan Cancer Institute	Providence	Rhode Island
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin		Cycle 1 to Cycle 2 (cycle length = 21 days)
Primary	Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin		Cycle 1 to Cycle 2 (cycle length = 21 days)
Primary	Percentage of Participants with Adverse Events (AE)		Baseline through approximately 90 days after last study treatment
Primary	Best Objective Response Rate (ORR), Defined as CR or Partial Response (PR) at any Time, Based on PET-CT and/or CT Scan, as Determined by the Independent Review Committee (IRC) using Standard Criteria for NHL		Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Secondary	Best ORR (CR or PR at any Time) Based on PET-CT and/or CT Scan, as Determined by the Investigator Using Standard Criteria for NHL		Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Secondary	Best CR Rate on Study Based on PET-CT, and/or CT Scan, as Determined by the Investigator and IRC Using Standard Criteria for NHL		Baseline up to approximately 60 months (assessed at screening and then every 3 months for the first year, then every 6 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Secondary	CR Rate at the Time of Primary Response Assessment (PRA) Based on PET-CT, as Determined by the Investigator and IRC Using Standard Criteria for NHL		Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Secondary	ORR, Defined as CR or PR, at PRA Based on PET-CT as Determined by the Investigator and IRC Using Standard Criteria for NHL		Cycle 8 completion (participants receiving mosunetuzumab), or 5-7 weeks after Cycle 6 (polatuzumab+bendamustine+rituximab participants) (Cycle = 21 days)
Secondary	Duration of Response (DOR) as Determined by the Investigator and IRC Using Standard Criteria for NHL		From the first occurrence of a documented response to disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Secondary	Progression-Free Survival (PFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL		From time of first study treatment to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 60 months)
Secondary	Event-Free Survival (EFS) as Determined by the Investigator and IRC Using Standard Criteria for NHL		From time of first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death from any cause, whichever occurs first (up to approximately 60 months)
Secondary	Overall Survival (OS)		From time of first study treatment to death from any cause (up to approximately 60 months)
Secondary	Anti-Drug Antibodies (ADAs) to Mosunetuzumab		At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Secondary	ADAs to Polatuzumab Vedotin		At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment
Secondary	Mosunetuzumab Serum Concentration		At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment