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

NCT05169515 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CO43805
• Study Type: interventional
• Target: 121
• Locations: 5 countries
• Sites: 26

Brief Summary

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.

Conditions

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation]

  Until 90 days after the final dose of study treatment

• Percentage of participants with adverse events [all cohorts]

  Until 90 days after the final dose of study treatment

• Best overall response rate (ORR), defined as the proportion of participants whose best overall response is a partial response (PR) or a complete response (CR) during the study, as determined by the investigator using Lugano 2014 criteria [dose expansion]

  Up to 2 years after start of primary study treatment

• Tolerability, as assessed by the incidence of dose interruptions, dose reductions, dose intensity, and treatment discontinuation [dose escalation]

  Until 90 days after the final dose of study treatment

Secondary Outcomes (11)

• Best CR rate, defined as the proportion of participants whose best overall response is a CR during the study, as determined by the investigator using Lugano 2014 criteria [all cohorts]

  Up to 1 year after primary study treatment

• Best ORR (CR or PR at any time) on study as determined by the investigator using Lugano 2014 criteria [dose escalation]

  Up to 2 years after primary study treatment

• Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts]

  Up to 2 years after primary study treatment

• Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]

  Up to 2 years after primary study treatment

• Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]

  Up to 2 years after primary study treatment

Study Arms (2)

Arm 1

EXPERIMENTAL

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

Drug: SC Mosunetuzumab; Drug: Iberdomide; Drug: Golcadomide; Drug: Tocilizumab

Arm 2

EXPERIMENTAL

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

Drug: IV Glofitamab; Drug: Golcadomide; Drug: Obinutuzumab; Drug: Tocilizumab

Interventions

SC Mosunetuzumab 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)

Also known as: RO7030816

Arm 1

IV Glofitamab DRUG

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

Also known as: RO7082859

Arm 2

Iberdomide 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)

Also known as: CC-220

Arm 1

Golcadomide 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)

Also known as: CC-99282

Arm 1; Arm 2

Obinutuzumab DRUG

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

Also known as: RO5072759

Arm 2

Tocilizumab DRUG

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

Also known as: RO4877533

Arm 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (26)

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

San Francisco, California, 94143, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Soroka

Beersheba, 0084101, Israel

RECRUITING

Rambam Health Care Campus

Haifa, 3109600, Israel

RECRUITING

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

RECRUITING

Center Hospital

Ramat Gan, 5262199, Israel

RECRUITING

Sourasky Medical Center

Tel Aviv, 6423900, Israel

RECRUITING

IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

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

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

ASST Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

RECRUITING

Irccs Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia

Pisa, Piedmont, 56126, Italy

RECRUITING

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario La Fe

Valencia, Valencia, 46026, Spain

RECRUITING

Hospital Universitari Vall d Hebron

Barcelona, 08035, Spain

RECRUITING

Clinica Universidad de Navarra-Madrid

Madrid, 28027, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28040, Spain

RECRUITING

Hosp Universitario Salamanca

Salamanca, 37007, Spain

RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, G12 0YN, United Kingdom

RECRUITING

University College London Hospitals

London, W1T 7HA, United Kingdom

RECRUITING

Nottingham University Hospitals City Campus

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

glofitamab; iberdomide; obinutuzumab; tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Study Design

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

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 27, 2021
• Study Start: October 26, 2022
• Primary Completion (Estimated): September 15, 2029
• Study Completion (Estimated): September 15, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); IL (5); IT (5); ES (6); US (6)