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

NCT03671018 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: GO405162018-001141-13
• Study Type: interventional
• Target: 422
• Locations: 5 countries
• Sites: 29

Brief 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.

Conditions

B-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin

  Cycle 1 to Cycle 2 (cycle length = 21 days)

• Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin

  Cycle 1 to Cycle 2 (cycle length = 21 days)

• Percentage of Participants with Adverse Events (AE)

  Baseline through approximately 90 days after last study treatment

• 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 Outcomes (11)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (5)

Dose Finding

EXPERIMENTAL

Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.

Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab

Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL

EXPERIMENTAL

Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.

Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab

Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

EXPERIMENTAL

2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.

Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab; Drug: Rituximab

Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

EXPERIMENTAL

Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.

Drug: Mosunetuzumab (SC); Drug: Polatuzumab vedotin; Drug: Tocilizumab

Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL

EXPERIMENTAL

2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.

Drug: Mosunetuzumab (SC); Drug: Polatuzumab vedotin; Drug: Tocilizumab

Interventions

Mosunetuzumab (IV) DRUG

Participants will receive intravenous (IV) mosunetuzumab.

Also known as: BTCT4465A

Dose Finding; Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL; Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

Mosunetuzumab (SC) DRUG

Participants will receive subcutaneous (SC) mosunetuzumab.

Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL; Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

Polatuzumab vedotin DRUG

Participants will receive IV polatuzumab vedotin.

Dose Finding; Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL; Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL; Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL; Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

Tocilizumab DRUG

Participants will receive IV tocilizumab as needed.

Dose Finding; Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL; Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL; Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL; Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

Rituximab DRUG

Participants will receive IV rituximab.

Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (29)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 35249, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232-1301, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02905, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin, Froedtert Hospital;Nephrology Section

Milwaukee, Wisconsin, 53226, United States

Location

UZ Brussel

Brussels, 1090, Belgium

Location

CH Jolimont - Lobbes (Jolimont)

Haine-Saint-Paul, 7100, Belgium

Location

Clinique St Pierre asbl

Ottignies, 1340, Belgium

Location

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC)

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital de San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Infanta Leonor; Servicio de Hematologia

Madrid, 28031, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Plymouth Hospitals NHS Trust; Pharmacy Dept

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (1)

• Budde LE, Olszewski AJ, Assouline S, Lossos IS, Diefenbach C, Kamdar M, Ghosh N, Modi D, Sabry W, Naik S, Mehta A, Nakhoda SK, Smith SD, Dorritie K, Jia T, Pham S, Huw LY, Jing J, Wu H, Ead WS, To I, Batlevi CL, Wei MC, Chavez JC. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med. 2024 Jan;30(1):229-239. doi: 10.1038/s41591-023-02726-5. Epub 2023 Dec 10.

  PMID: 38072960 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

polatuzumab vedotin; tocilizumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 14, 2018
• Study Start: September 25, 2018
• Primary Completion: January 30, 2024
• Study Completion: July 20, 2025
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); GB (2); US (16); ES (5); BE (3)