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
- Conditions
- Non-Hodgkin Lymphoma
- Registration Number
- NCT05169515
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> - Age >/= 18 years<br><br> - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2<br><br> - History of one of the following histologically documented hematologic malignancies<br> that are expected to express the CD20 antigen: In the Dose Escalation phase,<br> patients with R/R NHL who previously received at least two prior lines of systemic<br> therapies can be enrolled. In the Dose Expansion phase, patients with FL (grade<br> 1-3a), DLBCL/transformed FL who failed to respond to at least one prior line of<br> systemic therapy can be potentially enrolled<br><br> - Fluorodeoxyglucose-avid lymphoma (i.e. PET-positive lymphoma)<br><br> - At least one bi-dimensionally measurable nodal lesion (> 1.5 cm in its largest<br> dimension by diagnostic quality CT or PET/CT scan), or at least one bi-dimensionally<br> measurable extranodal lesion (> 1.0 cm in its largest dimension by diagnostic<br> quality CT or PET/CT scan)<br><br> - Availability of a representative tumor specimen and the corresponding pathology<br> report for confirmation of the diagnosis of NHL<br><br> - A fresh pretreatment biopsy during screening period, excisional or incisional, is<br> preferred<br><br> - Adequate hematologic function without growth factors or blood product transfusion<br> within 14 days of first dose of study drug administration<br><br> - Normal laboratory values<br><br> - All participants and health care providers will be trained and counseled on<br> pregnancy prevention. For female participants of childbearing potential: agreement<br> to remain abstinent (refrain from heterosexual intercourse) or use contraception<br> during the treatment period and for 3 months after the final dose of mosunetuzumab,<br> at least 18 months after pre-treatment with obinutuzumab or 2 months after the last<br> dose of glofitamab, 28 days after the last dose of CC-220, 6 months and 2 weeks<br> after the last dose of CC-99282, 3 months after the last dose of tocilizumab (if<br> applicable), whichever is longer<br><br> - For male participants: agreement to remain abstinent (refrain from heterosexual<br> intercourse) or use a condom, and agree to refrain from donating sperm during the<br> treatment period and for at least 3 months after pre-treatment with obinutuzumab or<br> 2 months after the last dose of glofitamab, 90 days after the last dose of CC-220, 3<br> months and 2 weeks after the last dose of CC- 99282, 2 months after the final dose<br> of tocilizumab (if applicable), whichever is longer<br><br>Exclusion Criteria:<br><br> - Pregnancy or breastfeeding, or intention of becoming pregnant during the study<br> (female participants of childbearing potential must have a negative serum pregancy<br> test result within 14 days prior to initiation of the study treatment)<br><br> - Participant has received prior therapy with cereblon (CRBN)-modulating drug (e.g.,<br> lenalidomide, avadomide/CC-122, pomalidomide) </= 4 weeks prior to starting CC-220<br> and/or CC-99282<br><br> - Inability to swallow pills, or persistent diarrhea or malabsorption >= Grade 2<br> National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events<br> (CTCAE), despite medical management<br><br> - QTc interval of > 470 ms<br><br> - The following treatments prior to study entry: mosunetuzumab, glofitamab, or other<br> CD20/CD3-directed bispecific antibodies; allogenic stem cell therapy (SCT); solid<br> organ transplantation<br><br> - Treatments (investigation or approved) within the following time periods prior to<br> initiation/first dose of study treatment: radiotherapy within 2 weeks; autologous<br> SCT within 100 days; chimeric antigen receptor (CAR) T-cell therapy within 30 days;<br> prior anti-lymphoma treatment with monoclonal antibodies or antibody-drug conjugates<br> within 4 weeks; use of radioimmunoconjugates within 12 weeks; systemic<br> immunosuppressive medications within 2 weeks; any other anti-cancer therapy, whether<br> investigational or approved, including but not limited to chemotherapy, within 4<br> weeks or 5 half-lives of the drug, whichever is shorter<br><br> - Live, attenuated vaccine within 4 weeks before first dose of study treatment, or in<br> whom it is anticipated that such a live attenuated vaccine will be required during<br> the study period or within 5 months after the final dose of study treatment<br><br> - Current or past history of central nervous system (CNS) lymphoma or leptomeningeal<br> infiltration<br><br> - History of severe allergic or anaphylactic reactions to humanized or murine<br> monoclonal antibody therapy (or recombinant antibody-related fusion proteins)<br><br> - History of autoimmune disease, including but not limited to myocarditis,<br> pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus<br> erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis<br> associated with antiphospholipid syndrome, granulomatosis with polyangiitis,<br> Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or<br> glomerulonephritis<br><br> - Major surgery or significant traumatic injury < 28 days prior to enrollment<br> (excluding biopsies) or anticipation of the need for major surgery during study<br> treatment<br><br> - Clinically significant toxicities from prior treatment have not resolved to Grade<br> </= 1 (per US national cancer institute (NCI) common terminology criteria for<br> adverse events (CTCAE) v5.0) prior to the first study drug administration with<br> exceptions defined by the protocol<br><br> - Evidence of any significant, concomitant disease (e.g. cardiovascular, pulmonary,<br> liver, CVA or stroke, ILD, PML, infection, HLH etc) that could affect compliance<br> with the protocol or interpretation of results<br><br> - For participants enrolled into glofitamab cohort: documented refractoriness to an<br> obinutuzumab monotherapy-containing regimen (defined as disease that did not achieve<br> response (PR or CR) or progressed within 6 months of the last dose of an<br> obinutuzumab-containing regimen)
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation];Percentage of participants with adverse events [dose escalation];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]
- Secondary Outcome Measures
Name Time Method 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];Best ORR (CR or PR at any time) on study as determined by the investigator using Lugano 2014 criteria [dose escalation];Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts];Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion];Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion];Overall survival (OS) [dose expansion];Percentage of participants with adverse events [dose expansion];Serum concentration of subcutaneous (SC) mosunetuzumab [all cohorts];Serum concentration of intravenous (IV) glofitamab [all cohorts];Serum concentration of CC-220 and CC-99282 (CELMoDs) [all cohorts]