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B-cell Non-Hodgkin LymphomaPhase 1/2NCT03671018

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

A Phase 1/2 study testing Mosunetuzumab (IV), Mosunetuzumab (SC) and Polatuzumab vedotin in people with B-cell Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 29 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-cell Non-Hodgkin Lymphoma
What is being tested?
Mosunetuzumab (IV), Mosunetuzumab (SC) and Polatuzumab vedotin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
422 participants
Where
29 sitesin 5 countries
Study dates
25 Sep 2018to 20 Jul 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

29 sites in 5 countries.

29 sites in 5 countries

United States16 sites

  • University of Michigan Hospital

    Ann Arbor, Michigan, 48109

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham School of Medicine

    Birmingham, Alabama, 35249

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Medical College of Wisconsin, Froedtert Hospital;Nephrology Section

    Milwaukee, Wisconsin, 53226

  • New York University Langone Medical Center

    New York, New York, 10016

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of Pittsburgh - Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232-1301

  • Lifespan Cancer Institute

    Providence, Rhode Island, 02905

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Spain5 sites

  • Institut Catala d Oncologia Hospital Duran i Reynals

    Barcelona, 08908

  • Hospital de San Pedro de Alcantara

    Cáceres, 10003

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Infanta Leonor; Servicio de Hematologia

    Madrid, 28031

  • Hospital Universitario Virgen Macarena; Servicio de Oncologia

    Seville, 41009

Other trials in Spain

Belgium3 sites

  • UZ Brussel

    Brussels, 1090

  • CH Jolimont - Lobbes (Jolimont)

    Haine-Saint-Paul, 7100

  • Clinique St Pierre asbl

    Ottignies, 1340

Other trials in Belgium

Canada3 sites

  • Hamilton Health Sciences - Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

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

    Saskatoon, Saskatchewan, S7N 4H4

Other trials in Canada

United Kingdom2 sites

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Plymouth Hospitals NHS Trust; Pharmacy Dept

    Plymouth, PL6 8DH

Other trials in United Kingdom

About this study

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

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.

Being tested
Mosunetuzumab (IV), Mosunetuzumab (SC), Polatuzumab vedotin, Tocilizumab, Rituximab
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mosunetuzumab (IV)Drug

    Also called BTCT4465A

    Participants will receive intravenous (IV) mosunetuzumab.

  • Mosunetuzumab (SC)Drug

    Participants will receive subcutaneous (SC) mosunetuzumab.

  • Polatuzumab vedotinDrug

    Participants will receive IV polatuzumab vedotin.

  • TocilizumabDrug

    Participants will receive IV tocilizumab as needed.

  • RituximabDrug

    Participants will receive IV rituximab.

Study groups in NCT03671018
Study groupRoleWhat they receive
Dose FindingExperimentalParticipants 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.
Receives: Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab
Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FLExperimentalParticipants 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.
Receives: Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab
Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCLExperimental2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.
Receives: Drug: Mosunetuzumab (IV); Drug: Polatuzumab vedotin; Drug: Tocilizumab; Drug: Rituximab
Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCLExperimentalParticipants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.
Receives: Drug: Mosunetuzumab (SC); Drug: Polatuzumab vedotin; Drug: Tocilizumab
Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCLExperimental2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.
Receives: Drug: Mosunetuzumab (SC); Drug: Polatuzumab vedotin; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

  2. Recommended Phase II Dose of Mosunetuzumab in Combination with Polatuzumab Vedotin

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

  3. Percentage of Participants with Adverse Events (AE)

    Measured: 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

    Measured: 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)

  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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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)

    Measured: From time of first study treatment to death from any cause (up to approximately 60 months)

  9. Anti-Drug Antibodies (ADAs) to Mosunetuzumab

    Measured: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

  10. ADAs to Polatuzumab Vedotin

    Measured: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

  11. Mosunetuzumab Serum Concentration

    Measured: At pre-defined intervals from C1D1 through approximately 90 days after the last study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2018
  2. Study start25 Sep 2018
  3. Primary completion30 Jan 2024
  4. Study completion20 Jul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
422 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03671018
Sponsor's protocol ID
GO40516
Other IDs
2018-001141-13, 2018
Status last verified
Nov 2024
First submitted
10 Sep 2018
Last updated
29 Nov 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Publications

  • Chavez JC, Bastos-Oreiro M, Diefenbach C, Lossos IS, Shah N, Assouline S, Olszewski AJ, Naik S, Ghosh N, Pham S, Wei MC, Batlevi C, To I, Ead W, Makadia S, Penuel E, Jing J, Budde LE. A Randomized Phase II Study of Subcutaneous Mosunetuzumab in Combination With Polatuzumab Vedotin Compared With Rituximab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Large B-Cell Lymphoma. Am J Hematol. 2026 Sep;101(9):2177-2189. doi: 10.1002/ajh.70403. Epub 2026 Jun 12.

    PubMed 42283231

  • Budde LE, Kamdar M, Assouline SE, Chavez JC, Ghosh N, Ollila TA, Hodson DJ, Modi D, Bastos-Oreiro M, Naik SG, Nakhoda SK, Lee Batlevi C, Wang J, Makadia S, Kwan A, Penuel E, Jing J, Wu H, Ead W, Pham S, To I, Wei MC, Wang ML. Mosunetuzumab plus polatuzumab vedotin for relapsed/refractory MCL after BTK inhibitor therapy: a phase 2 study. Blood. 2026 Aug 6;148(6):682-692. doi: 10.1182/blood.2025032422.

    PubMed 42013019

  • 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.

    PubMed 38072960

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mosunetuzumab (IV), Mosunetuzumab (SC) and Polatuzumab vedotin in people with B-cell Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 29 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Spain, Belgium, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Mosunetuzumab in Combination with Polatuzumab Vedotin (time frame: Cycle 1 to Cycle 2 (cycle length = 21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03671018, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.

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