A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and/or CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT05169515

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-26

Study Completion Date

2029-09-15

Brief Summary

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This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 and/or CC-99282) in participants with B-cell NHL.

Detailed Description

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Conditions

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Non-Hodgkin Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.

Group Type EXPERIMENTAL

SC Mosunetuzumab

Intervention Type DRUG

Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days or 28 days for Cycle 1 and 28 days for Cycles 2-12)

Iberdomide

Intervention Type DRUG

Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)

Golcadomide

Intervention Type DRUG

Arm 1: Participants will receive oral golcadomide from Day 1-14 starting in either Cycle 1 or Cycle 2 through Cycle 12 (cycle length = 28 days for cycles when golcadomide is to be administered) Arm 2: Participants will receive oral golcadomide from Day 1-10 starting in either Cycle 1, Cycle 2 or Cycle 3 through Cycle 12 (cycle length = 21 days)

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)

Arm 2

Participants will receive intravenous (IV) glofitamab + CC-99282.

Group Type EXPERIMENTAL

IV Glofitamab

Intervention Type DRUG

Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days)

Golcadomide

Intervention Type DRUG

Arm 1: Participants will receive oral golcadomide from Day 1-14 starting in either Cycle 1 or Cycle 2 through Cycle 12 (cycle length = 28 days for cycles when golcadomide is to be administered) Arm 2: Participants will receive oral golcadomide from Day 1-10 starting in either Cycle 1, Cycle 2 or Cycle 3 through Cycle 12 (cycle length = 21 days)

Obinutuzumab

Intervention Type DRUG

Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)

Interventions

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SC Mosunetuzumab

Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days or 28 days for Cycle 1 and 28 days for Cycles 2-12)

Intervention Type DRUG

IV Glofitamab

Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days)

Intervention Type DRUG

Iberdomide

Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)

Intervention Type DRUG

Golcadomide

Arm 1: Participants will receive oral golcadomide from Day 1-14 starting in either Cycle 1 or Cycle 2 through Cycle 12 (cycle length = 28 days for cycles when golcadomide is to be administered) Arm 2: Participants will receive oral golcadomide from Day 1-10 starting in either Cycle 1, Cycle 2 or Cycle 3 through Cycle 12 (cycle length = 21 days)

Intervention Type DRUG

Obinutuzumab

Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)

Intervention Type DRUG

Tocilizumab

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)

Intervention Type DRUG

Other Intervention Names

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RO7030816 RO7082859 CC-220 CC-99282 RO5072759 RO4877533

Eligibility Criteria

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Inclusion Criteria

* Age \>/= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* History of one of the following histologically documented hematologic malignancies that are expected to express the CD20 antigen: In the Dose Escalation phase, participants must have relapsed after or failed to respond to at least two prior lines of systemic therapy. In the Dose Expansion phase, participants with FL Grades 1-3a must have relapsed after or failed to respond to at least one prior line of systemic therapy and must require systemic therapy. Participants with DLBCL/transformed FL must have relapsed after or failed to respond to at least one prior systemic treatment regimen.
* Participants with DLBCL/transformed FL who have received only one prior line of therapy must: Not be considered a candidate for autologous stem cell transplantation (ASCT) due to age, performance status, comorbidities and/or insufficient response to prior treatment, or have refused ASCT; or be ineligible for or unable to receive chimeric antigen receptor T-cell (CAR-T) therapy due to reasons defined by the protocol
* Fluorodeoxyglucose-avid lymphoma (i.e. PET-positive lymphoma)
* At least one bi-dimensionally measurable nodal lesion (\> 1.5 cm in its largest dimension by diagnostic quality CT or PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion (\> 1.0 cm in its largest dimension by diagnostic quality CT or PET/CT scan)
* Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of NHL
* A fresh pretreatment biopsy during screening period, excisional or incisional, is preferred
* Adequate hematologic function without growth factors or blood product transfusion within 14 days of first dose of study drug administration
* Normal laboratory values
* All participants and health care providers will be trained and counseled on pregnancy prevention. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 3 months after the final dose of mosunetuzumab, at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 28 days after the last dose of CC-99282, 3 months after the last dose of tocilizumab (if applicable), whichever is longer
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 28 days after the last dose of CC- 99282, 2 months after the final dose of tocilizumab (if applicable), whichever is longer

Exclusion Criteria

* Pregnancy or breastfeeding, or intention of becoming pregnant during the study (female participants of childbearing potential must have a negative serum pregancy test result within 14 days prior to initiation of the study treatment) or within 3 months after the final dose of mosunetuzumab, at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer, 28 days after the last dose of CC-220, 28 days after the last dose of CC-9282, 3 months after the final dose of tocilizumab, whichever is longer
* Participant has received prior therapy with cereblon (CRBN)-modulating drug (e.g., lenalidomide, avadomide/CC-122, pomalidomide) \</= 4 weeks prior to starting CC-220 and/or CC-99282
* Inability to swallow pills, or persistent diarrhea or malabsorption \>= Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), despite medical management
* QTc interval of \> 470 ms
* The following treatments prior to study entry: mosunetuzumab, glofitamab, or other CD20/CD3-directed bispecific antibodies; allogenic stem cell therapy (SCT); solid organ transplantation
* Treatments (investigational or approved) within the following time periods prior to initiation/first dose of study treatment: radiotherapy within 2 weeks; autologous SCT within 100 days; chimeric antigen receptor (CAR) T-cell therapy within 30 days; prior anti-lymphoma treatment with monoclonal antibodies or antibody-drug conjugates within 4 weeks; use of radioimmunoconjugates within 12 weeks; systemic immunosuppressive medications within 2 weeks; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter
* Live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment
* Current or past history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
* History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* Major surgery or significant traumatic injury \< 28 days prior to enrollment (excluding biopsies) or anticipation of the need for major surgery during study treatment
* Clinically significant toxicities from prior treatment have not resolved to Grade \</= 1 (per US national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5.0) prior to the first study drug administration with exceptions defined by the protocol
* Evidence of any significant, concomitant disease (e.g. cardiovascular, pulmonary, liver, CVA or stroke, ILD, PML, infection, HLH etc) that could affect compliance with the protocol or interpretation of results
* For participants enrolled into glofitamab cohort: documented refractoriness to an obinutuzumab monotherapy-containing regimen (defined as disease that did not achieve response (PR or CR) or progressed within 6 months of the last dose of an obinutuzumab-containing regimen)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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UCSF/Hematology, Blood & Marrow Transplant, And Cellular Therapy (HBC) Program

San Francisco, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

The University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Soroka

Beersheba, , Israel

Site Status RECRUITING

Rambam Health Care Campus

Haifa, , Israel

Site Status RECRUITING

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Site Status RECRUITING

Center Hospital

Ramat Gan, , Israel

Site Status RECRUITING

Sourasky Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, Emilia-Romagna, Italy

Site Status RECRUITING

IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"

Meldola, Emilia-Romagna, Italy

Site Status RECRUITING

ASST Spedali Civili di Brescia

Brescia, Lombardy, Italy

Site Status RECRUITING

Irccs Ospedale San Raffaele

Milan, Lombardy, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia

Pisa, Piedmont, Italy

Site Status RECRUITING

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario La Fe

Valencia, Valencia, Spain

Site Status RECRUITING

Hospital Universitari Vall d Hebron

Barcelona, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra-Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status RECRUITING

Hosp Universitario Salamanca

Salamanca, , Spain

Site Status RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status RECRUITING

University College London Hospitals

London, , United Kingdom

Site Status RECRUITING

Nottingham University Hospitals City Campus

Nottingham, , United Kingdom

Site Status RECRUITING

Oxford University Hospitals NHS Trust;Churchill Hospital

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United States Israel Italy Spain United Kingdom

Central Contacts

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Reference Study ID Number: CO43805 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728

Email: [email protected]

Other Identifiers

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CO43805

Identifier Type: -

Identifier Source: org_study_id