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A clinical trial to test CC-220 or CC-99282 in combination with mosunetuzumab or glofitamab in people with B-cell non-Hodgkin lymphoma.
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
- Non-Hodgkin's Lymphoma
Trial Status:
Recruiting
This trial runs in
Cities
- Be'er Sheva
- Bologna
- Chicago
- Haifa
- Jerusalem
- Lombardy
- London
- Madrid
- Nottingham
- Oxford
- Pisa
- Ramat Gan
- Salamanca
- San Francisco
- Tel Aviv-Yafo
- València
Trial Identifier:
NCT05169515 CO43805
Trial 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.
Hoffmann-La Roche
Sponsor
Phase 1
Phase
NCT05169515 , CO43805
Trial Identifier
All
Gender
≥18 Years
Age
No
Healthy Volunteers
Why is the CO43805 clinical trial needed?
B-cell non-Hodgkin lymphoma (NHL) is a common type of cancer that affects a type of immune cell called B cells. Although there has been progress in treating NHL, many people who have NHL may not respond to treatment (their disease is refractory) or will experience a relapse (their disease will get worse). This trial aims to test whether new drug combinations could help people with relapsed or refractory NHL to live longer, without intolerable side effects.
How does the CO43805 clinical trial work?
This clinical trial is recruiting people who have a health condition called B-cell NHL. People can take part if they have relapsed or refractory NHL.
The purpose of this clinical trial is to test the safety and effectiveness of CC-220 or CC-99282 when combined with mosunetuzumab or glofitamab and to understand the way the body processes these combinations.
Participants will be given the clinical trial treatment CC-220 or CC-99282 in combination with mosunetuzumab (Group A) OR CC-220 or CC-99282 in combination with glofitamab (Group B) for up to 12 cycles of treatment. Participants will be seen by the clinical trial doctor every week during the first two to three cycles, then every 3 or 4 weeks in the remaining treatment cycles. These hospital visits will include checks to see how the participant is responding to the treatment and any side effects they may be having. Participants’ total time in the clinical trial will be up to roughly 3 years, as they will be seen for follow-up appointments every 3 months for 2 years after they have finished treatment. Participants are free to stop trial treatment and leave the clinical trial at any time.
What are the main endpoints of the CO43805 clinical trial?
The main clinical trial endpoints (the main results that are measured in the trial to see if the medicine has worked) are the type and number of dose-limiting toxicities (DLTs) and adverse events (AEs). DLTs are treatment side effects that are too severe to allow for an increase in the dose, and AEs are any unexpected medical problems that occur while receiving the treatment.
Other clinical trial endpoints include the proportion of people who respond to their treatment during the clinical trial (complete response rate and overall response rate) and how long their response lasts (duration of response).
Who can take part in this clinical trial?
People can take part in this trial if they are at least 18 years old and have NHL that either failed to respond or relapsed after treatment with at least two previous lines of systemic therapy (treatment that travels through the bloodstream).
People will not be able to take part in this trial if they are pregnant or breastfeeding, have certain other medical conditions or have previously received certain other treatments.
What treatment will participants be given in this clinical trial?
Everyone who joins this clinical trial will be put into groups depending on when they join and given either:
- Group A: Mosunetuzumab as an injection under the skin (subcutaneous) on Days 1, 8 and 15 of Cycle 1, then Day 1 of Cycles 2–12 and CC-220 as a capsule to be swallowed once a day on Days 1–21 of Cycles 2–12 OR CC-99282 as a capsule to be swallowed once a day on Days 1–14 of Cycles 2–12. Cycle 1 will last for 21 days and Cycles 2–12 will last for 28 days
- Group B: Glofitamab as an infusion into the vein on Days 8 and 15 of Cycle 1, then Day 1 of Cycles 2–12, and CC-220 as a capsule to be swallowed once a day on Days 1–14 of Cycles 3–12 OR CC-99282 as a capsule to be swallowed once a day on Days 1–10 of Cycles 3–12. Each cycle will last for 21 days. People in this group will also need to have one pre-treatment dose of obinutuzumab as an infusion into the vein on Day 1 of Cycle 1
Participants may also receive tocilizumab as an infusion into the vein if they experience certain side effects during the clinical trial.
This is an open-label clinical trial, which means that all participants will know which treatment they are receiving.
Are there any risks or benefits in taking part in this clinical trial?
The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant, although it may not be greater than the risks related to routine medical care or the natural progression of the health condition. Potential participants will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. These will all be described in an informed consent document (a document that provides people with the information they need to make a decision to volunteer for a clinical trial). A potential participant should also discuss these with members of the research team and with their usual healthcare provider. Anyone interested in taking part in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.
Risks associated with the clinical trial drugs
Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening, and can vary from person to person.
Mosunetuzumab
Potential participants will be told about the known side effects of mosunetuzumab and, where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
Mosunetuzumab will be given as a subcutaneous injection (inserting a needle into the fatty layer between the skin and muscle). Participants will be told about any known side effects of subcutaneous injections.
Glofitamab, obinutuzumab and tocilizumab
Potential participants will be told about the known side effects of glofitamab, obinutuzumab and tocilizumab and, where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
Glofitamab, obinutuzumab and tocilizumab are each given as an intravenous infusion (inserting a needle into a vein, usually in the arm). Participants will be told about any known side effects of intravenous infusions.
CC-220 and CC-99282
Potential participants will be told about the known side effects of CC-220 and CC-99282 and, where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
CC-220 and CC-99282 are each given as capsules to be swallowed with water (oral administration). Participants will be told about any known side effects of oral administration.
Potential benefits associated with the clinical trial
Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.
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For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT05169515
Trial 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.
Hoffmann-La Roche
Sponsor
Phase 1
Phase
NCT05169515 , CO43805
Trial Identifier
SC Mosunetuzumab, IV Glofitamab, CC-220, CC-99282, Obinutuzumab, Tocilizumab
Treatments
Non-Hodgkin Lymphoma
Condition
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
Eligibility Criteria
All
Gender
≥18 Years
Age
No
Healthy Volunteers
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, 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, 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
For the latest version of this information please go to www.forpatients.roche.com