Clinical Trial 21710

• Overview

  Study Title:

  A Phase 1b, Open-Label, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitabmab in Combination with CC-220 and CC-99282 in Patients with B-Cell Non-Hodgkin Lymphoma

  Objective:

  Dose Escalation: 1. To evaluate the safety and select the RP2D of CELMoDs (CC-220 and CC-99282) in combination with mosunetuzumab SC in Cohort A1, Cohort A2, Cohort B1, and Cohort B2; 2. To evaluate the safety and select the RP2D of CELMoDs (CC-220 and CC-99282) in combination with glofitamab IV in Cohort C1, Cohort C2, Cohort D1, and Cohort D2; 3. To evaluate the preliminary efficacy of mosunetuzumab SC in combination with CELMoDs (CC-220 and CC-99282) in Cohort A1, Cohort A2, Cohort B1, and Cohort B2; 4. To evaluate the preliminary efficacy of glofitamab IV in combination with CELMoDs (CC-220 and CC-99282) in Cohort C1, Cohort C2, Cohort D1, and Cohort D2. Dose Expansion: 1. To evaluate the efficacy of mosunetuzumab SC in combination with CELMoDs (CC-220 or CC-99282) in Cohort E; 2. To evaluate the efficacy of glofitamab IV in combination with CELMoDs (CC-220 or CC-99282) in Cohort F; 3. To evaluate the safety of mosunetuzumab SC in combination with CELMoDs (CC-220 and CC-99282) in Cohort E; 4. To evaluate the safety of glofitamab IV in combination with CELMoDs (CC-220 or CC-99282) in Cohort F. Escalation and Expansion: 1. To characterize the PK profile of mosunetuzumab SC in combination with CELMoDs in Cohort A1, Cohort A2, Cohort B1, Cohort B2 and Cohort E; 2. To characterize the PK profile of glofitamab IV in combination with CELMoDs in Cohort C1, Cohort C2, Cohort D1, Cohort D2 and Cohort F; 3. To characterize the PK of both CELMoDs when administered in combination with mosunetuzumab and glofitamab in Arm 1 and Arm 2, respectively.

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  CC-99282 (); Glofitamab (); Mosunetuzumab (); Tocilizumab ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Signed Informed Consent Form.
  • Age 18 years or older at the time of signing the Informed Consent Form.
  • Have a life expectancy (in the opinion of the investigator) of at least 12 weeks.
  • 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 as defined in 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 bidimensionaly 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. Cytological or fine-needle aspiration samples are not acceptable. If a pretreatment biopsy cannot be taken safely, a previously archived biopsy is acceptable that is preferably not older than 90 days and preferably not confounded by major events (e.g., treatment or progression since the biopsy was take), if available. Formalin fixed paraffin embedded blocks are preferred. If blocks are not available, 12 to 15 slides containing unstained, freshly cut, serial sections are acceptable.
  • Adequate hematologic function as defined by the protocol.
  • Normal laboratory values as defined by the protocol.
  • All participants and health care providers will be trained and counseled on pregnancy prevention in accordance with the CC-220 and CC-99282 Global Pregnancy Prevention Counseling Program prior to medication being dispensed to ensure that the patient has complied with all requirements, including use of birth control and pregnancy testing, and that the patient understands the risk of embryo-fetal toxicity associated with CC-220 and CC-99282. This step will be documented with a Completed Education and Counseling Guidance Document (refer to the CC-220 and CC-99282 Pregnancy Prevention Risk Management Plans), and no drug will be dispensed until this step occurs. Counseling includes verification with the patient that required pregnancy testing was performed, and results were negative. A CC-220 and CC-99282 Information Sheet will be supplied with each medication dispensed. All requirements must be followed by each site as noted in Pregnancy Prevention Risk Management Plans.
  • For all participants who receive CC-99282: must never donate blood while participating in this study, during dose interruptions and for at least 28 days after the last dose of CC-99282.
  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined in the protocol.
  • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined by the protocol.
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study 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, 6 months and 2 weeks after the last dose of CC-99282, 3 months after the final dose of tocilizumab (if applicable), whichever is longer.
  • Participant has received prior therapy with CRBN-modulating drug (e.g., lenalidomide, avadomide/CC-122, pomalidomide) 4 weeks or more 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 (QT interval corrected through use of Fridericia's formula or equivalent).
  • Treatments prior to study entry outlined in the protocol.
  • Treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment.
  • Radiotherapy within 2 weeks prior to the first dose of study treatment.
  • If participants have received radiotherapy within 4 weeks prior to the first study treatment administration, participants must have at least one measurable lesion outside of the radiation field.
  • Systemic corticosteroid treatment 10 mg or less prednisone or equivalent and inhaled corticosteroids are permitted.
  • Administration of acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea or B symptoms) is permitted.
  • The use of mineralocorticoids for management of orthostatic hypotension and corticosteroids for management of adrenal insufficiency is permitted.
  • 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 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, Sjögrens syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Major surgery or significant traumatic injury > Clinically significant toxicities from prior treatment that have not resolved to Grade 1 or 0 (per NCI CTCAE v5.0) prior to the first study drug administration.
  • Evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to A history of other malignancy that could affect compliance with the protocol or interpretation of results
  • Any of the following malignancies previously curatively treated: carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal, or squamous cell skin cancer.
  • prostate cancer with no evidence of metastatic disease and not on active therapy except for anti-androgen therapy.
  • Other exclusion criteria may apply.

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