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

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Patients With B-Cell Non-Hodgkin Lymphoma

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

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: SC Mosunetuzumab; Drug: CC-99282; Drug: Tocilizumab; Drug: IV Glofitamab; Drug: Obinutuzumab; Drug: CC-220

• Study Type: Interventional
• Enrollment (Estimated): 121
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO43805 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Israel
  • Be'er Sheva, Israel, 0084101
    • Recruiting
    • Soroka
  • Haifa, Israel, 3109600
    • Recruiting
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center; Pulmonary Institute
  • Ramat Gan, Israel, 5262199
    • Recruiting
    • Center Hospital
  • Tel-Aviv, Israel, 6423900
    • Recruiting
    • Sourasky Medical Center; Oncology Department
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero Universitaria di Bologna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Recruiting
      • IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Recruiting
      • ASST Spedali Civili di Brescia
    • Milano, Lombardia, Italy, 20132
      • Recruiting
      • Irccs Ospedale San Raffaele;U.O. Oculistica
  • Piemonte
    • Pisa, Piemonte, Italy, 56126
      • Recruiting
      • Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d Hebron
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra-Madrid
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp Universitario Salamanca
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • ICO L'Hospitalet; Servicio de Farmacia
  • Valencia
    • València, Valencia, Spain, 46026
      • Recruiting
      • Hospital Universitario La Fe; Hospital La Fe
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Withdrawn
    • Western General Hospital; Edinburgh Cancer Center
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • NHS Greater Glasgow and Clyde; Beatson West of Scotland Cancer Centre
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals
  • Nottingham, United Kingdom, NG5 1PB
    • Recruiting
    • Nottingham University Hospitals City Campus; Nottingham Cancer Clinical Trials Team
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Oxford University Hospitals NHS Trust; Churchill Hospital; Clinical Trials Pharmacy Department
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF/Hematology, Blood & Marrow Transplant, And Cellular Therapy (HBC) Program
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University Of Chicago
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT MD Anderson Cancer Center; Investigational Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, patients with R/R NHL who previously received at least two prior lines of systemic therapies can be enrolled. In the Dose Expansion phase, patients with FL (grade 1-3a), DLBCL/transformed FL who failed to respond to at least one prior line of systemic therapy can be potentially enrolled
• 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, 6 months and 2 weeks 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, 90 days after the last dose of CC-220, 3 months and 2 weeks 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)
• 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 (investigation 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 or SC mosunetuzumab + CC-99282.	Drug: SC Mosunetuzumab; Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days for Cycle 1 and 28 days for Cycles 2-12); Other Names: RO7030816; Drug: CC-99282; Arm 1: Participants will receive oral CC-99282 from Day 1-14 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12) Arm 2: Participants will receive oral CC-99282 from Day 1-10 of Cycle 3-12 (cycle length = 21 days); Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS); Other Names: RO4877533; Drug: CC-220; Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)
Experimental: Arm 2; Participants will receive intravenous (IV) glofitamab + CC-99282.	Drug: CC-99282; Arm 1: Participants will receive oral CC-99282 from Day 1-14 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12) Arm 2: Participants will receive oral CC-99282 from Day 1-10 of Cycle 3-12 (cycle length = 21 days); Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS); Other Names: RO4877533; Drug: IV Glofitamab; Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days); Other Names: RO7082859; Drug: Obinutuzumab; Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days); Other Names: RO5072759

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 [dose escalation]	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 1 year after start of primary study treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Overall survival (OS) [dose expansion]	Up to 2 years after primary study treatment
Percentage of participants with adverse events [dose expansion]	Until 90 days after the final dose of study treatment
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
Serum concentration of subcutaneous (SC) mosunetuzumab [all cohorts]	Up to 2 years after primary study treatment
Serum concentration of intravenous (IV) glofitamab [all cohorts]	Up to 2 years after primary study treatment
Serum concentration of CC-220 and CC-99282 (CELMoDs) [all cohorts]	Up to 12 cycles of study treatment (cycle length = 21 or 28 days for Arm 1 and 21 days for Arm 2)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2022
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2028

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: CO43805

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No