CLINICAL TRIAL / NCT05169515
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
- Interventional
- Recruiting
- NCT05169515
Contact Information
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.
Gender
All
Age Group
18 Years and up
Accepting 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 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)