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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03671018
Collaborator
(none)
262
Enrollment
29
Locations
4
Arms
61.8
Anticipated Duration (Months)
9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of intravenous mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), and in participants with follicular lymphoma (FL). 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 for the treatment of R/R mantle cell lymphoma (MCL).

Condition or Disease Intervention/Treatment Phase
  • Drug: Mosunetuzumab (IV)
  • Drug: Mosunetuzumab (SC)
  • Drug: Polatuzumab vedotin
  • Drug: Tocilizumab
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
262 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 25, 2018
Anticipated Primary Completion Date :
Jun 21, 2023
Anticipated Study Completion Date :
Nov 18, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Finding

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)
Participants will receive intravenous (IV) mosunetuzumab.
Other Names:
  • BTCT4465A

    • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.

    Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
    Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL

    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)
    Participants will receive intravenous (IV) mosunetuzumab.
    Other Names:
  • BTCT4465A

    • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.

    Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
    Experimental: Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

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

    Drug: Mosunetuzumab (IV)
    Participants will receive intravenous (IV) mosunetuzumab.
    Other Names:
  • BTCT4465A

    • Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.

    Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.
    Experimental: Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

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

    Drug: Mosunetuzumab (SC)
    Participants will receive subcutaneous (SC) mosunetuzumab.

    Drug: Polatuzumab vedotin
    Participants will receive IV polatuzumab vedotin.

    Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed.

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin [Cycle 1 to Cycle 2 (cycle length = 21 days)]

    2. Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin [Cycle 1 to Cycle 2 (cycle length = 21 days)]

    3. Percentage of Participants with Adverse Events (AE) [Baseline through approximately 90 days after last study treatment]

    4. 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 Outcome Measures

    1. 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)]

    2. 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)]

    3. 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)]

    4. 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)]

    5. 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)]

    6. 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)]

    7. 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)]

    8. Overall Survival (OS) [From time of first study treatment to death from any cause (up to approximately 60 months)]

    9. Anti-Drug Antibodies (ADAs) to Mosunetuzumab [At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment]

    10. ADAs to Polatuzumab Vedotin [At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment]

    11. Mosunetuzumab Serum Concentration [At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham School of Medicine Birmingham Alabama United States 352331912
    2 City of Hope Duarte California United States 91010
    3 University of Colorado Hospital - Anschutz Cancer Pavilion Aurora Colorado United States 80045
    4 University of Miami Miller School of Medicine Miami Florida United States 33136
    5 Moffitt Cancer Center Tampa Florida United States 33612
    6 University of Michigan Hospital Ann Arbor Michigan United States 48109
    7 Karmanos Cancer Institute Detroit Michigan United States 48201
    8 New York University Langone Medical Center New York New York United States 10016
    9 Levine Cancer Institute Charlotte North Carolina United States 28204
    10 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
    11 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    12 University of Pittsburgh - Hillman Cancer Center Pittsburgh Pennsylvania United States 15232-1301
    13 Lifespan Cancer Institute Providence Rhode Island United States 02905
    14 University of Texas M.D. Anderson Cancer Center Houston Texas United States 77030
    15 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    16 Medical College of Wisconsin, Froedtert Hospital;Nephrology Section Milwaukee Wisconsin United States 53226
    17 UZ Brussel Brussel Belgium 1090
    18 CH Jolimont - Lobbes (Jolimont) Haine-Saint-Paul Belgium 7100
    19 Clinique St Pierre asbl Ottignies Belgium 1340
    20 Hamilton Health Sciences - Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
    21 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    22 Saskatchewan Cancer Agency (SCA) - Saskatoon Cancer Centre (SCC) Saskatoon Saskatchewan Canada S7N 4H4
    23 Institut Catala d Oncologia Hospital Duran i Reynals Barcelona Spain 08908
    24 Hospital de San Pedro de Alcantara Caceres Spain 10003
    25 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    26 Hospital Infanta Leonor; Servicio de Hematologia Madrid Spain 28031
    27 Hospital Universitario Virgen Macarena; Servicio de Oncologia Sevilla Spain 41009
    28 Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom CB2 0QQ
    29 Plymouth Hospitals NHS Trust; Pharmacy Dept Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03671018
    Other Study ID Numbers:
    • GO40516
    • 2018-001141-13
    First Posted:
    Sep 14, 2018
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell

    Study Results

    No Results Posted as of Aug 5, 2022