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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05169515
Collaborator
(none)
112
2
56

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
112 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Anticipated Study Start Date :
Aug 15, 2022
Anticipated Primary Completion Date :
Apr 15, 2025
Anticipated Study Completion Date :
Apr 15, 2027

Arms and Interventions

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-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) Arm 2: Participants will receive oral CC-220 from Day 1-14 of Cycle 3-12 (cycle length = 21 days)

    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
  • Experimental: Arm 2

    Participants will receive intravenous (IV) glofitamab + CC-220 or IV glofitamab + CC-99282.

    Drug: IV Glofitamab
    Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days)
    Other Names:
  • RO7082859
  • 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) Arm 2: Participants will receive oral CC-220 from Day 1-14 of Cycle 3-12 (cycle length = 21 days)

    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: Obinutuzumab
    Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)
    Other Names:
  • RO5072759
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)
    Other Names:
  • RO4877533
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation] [Until 90 days after the final dose of study treatment]

    2. Percentage of participants with adverse events [dose escalation] [Until 90 days after the final dose of study treatment]

    3. 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 primary study treatment]

    Secondary Outcome Measures

    1. 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 2 years after primary study treatment]

    2. 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]

    3. Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts] [Up to 2 years after primary study treatment]

    4. Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion] [Up to 2 years after primary study treatment]

    5. Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion] [Up to 2 years after primary study treatment]

    6. Overall survival (OS) [dose expansion] [Up to 2 years after primary study treatment]

    7. Percentage of participants with adverse events [dose expansion] [Until 90 days after the final dose of study treatment]

    8. Maximum serum concentration (Cmax) of subcutaneous (SC) mosunetuzumab [all cohorts] [Up to 2 years after primary study treatment]

    9. Minimum serum concentration (Cmin) of mosunetuzumab SC [all cohorts] [Up to 2 years after primary study treatment]

    10. Total exposure (AUC) of mosunetuzumab SC [all cohorts] [Up to 2 years after primary study treatment]

    11. Apparent clearance (CL) of mosunetuzumab SC [all cohorts] [Up to 2 years after primary study treatment]

    12. Apparent volume of distribution of mosunetuzumab SC [all cohorts] [Up to 2 years after primary study treatment]

    13. Cmax of intravenous (IV) glofitamab [all cohorts] [Up to 2 years after primary study treatment]

    14. Cmin of glofitamab IV [all cohorts] [Up to 2 years after primary study treatment]

    15. AUC of glofitamab IV [all cohorts] [Up to 2 years after primary study treatment]

    16. CL of glofitamab IV [all cohorts] [Up to 2 years after primary study treatment]

    17. Volume of distribution of glofitamab IV [all cohorts] [Up to 2 years after primary study treatment]

    18. Cmax 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)]

    19. Cmin of 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)]

    20. CL of 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)]

    21. Volume of distribution of 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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm in its largest dimension by 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 and 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 and 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, Wegener's granulomatosis, 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

    Contacts and Locations

    Locations

    No locations specified.

    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:
    NCT05169515
    Other Study ID Numbers:
    • CO43805
    First Posted:
    Dec 27, 2021
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 5, 2022