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A clinical trial to look at the safety of cevostamab alone and in combination with other treatments in people with relapsed or refractory multiple myeloma
A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
- Cancer
- Multiple Myeloma
Please note that the recruitment status of the trial at your site may differ from the overall study status because some study sites may recruit earlier than others.
Trial Status:
Recruiting
This trial runs in
Countries
- Australia
- Canada
- Czechia
- Denmark
- France
- Israel
- Italy
- Poland
- South Korea
- Spain
- United Kingdom
- United States
Trial Identifier:
NCT04910568 2021-000238-33 GO42552
Trial Summary
This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab monotherapy, cevostamab plus pomalidomide and dexamethasone (Pd) or cevostamab plus daratumumab and dexamethasone (Dd) which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.
Genentech, Inc.
Sponsor
Phase 1
Phase
NCT04910568,GO42552,2021-000238-33
Trial Identifier
All
Gender
≥18 Years
Age
No
Healthy Volunteers
1. How does the CAMMA 1 clinical trial work?
This clinical trial is recruiting people who have a type of disease called multiple myeloma. In order to take part, participants must have relapsed disease (multiple myeloma that has become active again after effective treatment) or refractory disease (multiple myeloma that has not responded to treatment or has become resistant to it).
The purpose of this clinical trial is to understand how well cevostamab works and how safe it is when used alone or in combination with other drugs, such as pomalidomide and dexamethasone, or daratumumab and dexamethasone, to treat multiple myeloma.
2. How do I take part in this clinical trial?
To be able to take part in this clinical trial, you must be at least 18 years old and have been diagnosed with relapsed or refractory multiple myeloma. To receive cevostamab alone, participants should have no available, tolerable, or appropriate therapies (Group A); in order to receive cevostamab in combination with other multiple myeloma drugs, participants should have received previous treatment with certain multiple myeloma drugs including a proteasome inhibitor and an immunomodulatory drug (Group B and Group C).
You must not have already been treated with cevostamab or a similar drug. If you have previously received certain other medications or have other medical conditions that could interfere with the clinical trial, you may not be able to take part. You must not be pregnant or breastfeeding or intending to become pregnant during or shortly after the clinical trial.
If you think this clinical trial may be suitable for you and would like to take part, please talk to your doctor. If your doctor thinks that you might be able to take part in this clinical trial, he/she may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about taking part in the clinical trial. You can also find the clinical trial locations on this page.
You will have some further tests to make sure you will be able to take the treatments given in this clinical trial. Some of these tests or procedures may be part of your regular medical care. They may be done even if you do not take part in the clinical trial. If you have had some of the tests recently, they may not need to be done again.
Before starting the clinical trial, you will be told about any risks and benefits of taking part in the trial. You will also be told what other treatments are available so that you may decide if you still want to take part.
While taking part in the clinical trial, both men and women (if you are not currently pregnant but can become pregnant) will need to either not have heterosexual intercourse or use appropriate contraception for safety reasons.
3. What treatment will I be given if I join this clinical trial?
This is an open-label trial, which means everyone involved, including the participants and the doctors, know which clinical trial drugs are being used. Everyone who joins this clinical trial will be enrolled into one of three treatment groups depending on what treatments they have previously received. Treatments will be given regularly in ‘cycles’ - a treatment cycle is the treatment and recovery time before the next dose of treatment is given.
- Group A
- Cevostamab, as an infusion into the vein. Cevostamab will be given at different intervals throughout the treatment period (weekly, then every 2 weeks, and then every month).
- Group B
- Cevostamab, as an infusion into the vein. Cevostamab will be given as a pre-phase treatment on days 1, 8, and 15 before Cycle 1. Cevostamab will then be given on days 1 and 15 during cycles 1‒6 and then every 4 weeks from Cycle 7 onwards
- Pomalidomide, as a capsule to be swallowed every day from Cycle 1 on days 1‒21 of each 28-day cycle
- Dexamethasone, as an infusion into the vein on days 1, 8 and 15 during pre-phase, and days 1 and 15 during Cycle 1 as a pre-medication prior to cevostamab treatment. In Cycle 1, dexamethasone will also be given as an oral tablet on days 8 and 22. Dexamethasone will then be given as an oral tablet on days 1, 8, 15, and 22 of cycles 2‒4. The clinical trial doctor may decide that there is no need to give dexamethasone after Cycle 4.
- Group C
- Cevostamab, as an infusion into the vein. Cevostamab will be given on days 2, 9 and 16 during Cycle 1, then every 3 weeks during cycles 2‒8, and every 4 weeks from Cycle 9 onwards
- Daratumumab, as a subcutaneous (under the skin) injection. Daratumumab will be given on days 1, 8, and 15 during cycles 1‒3, then every 3 weeks during cycles 4‒8, and every 4 weeks from Cycle 9 onwards
- Dexamethasone, as an infusion into the vein on days 2, 9 and 16 during Cycle 1 and on day 1 of Cycle 2, as a pre-medication prior to cevostamab treatment. Dexamethasone may also be given as either oral tablet or as an infusion into the vein on days 1, 8 and 15 in Cycle 1, days 8 and 15 in Cycle 2 and on Day 1 in cycles 3–4. The clinical trial doctor may decide that there is no need to give dexamethasone after Cycle 4.
During this time, the clinical trial doctor will see participants regularly, at least every 1‒2 weeks and then on Day 1 of later cycles. Some participants may also be treated with a drug called tocilizumab if they experience specific side effects related to inflammation.
4. How often will I be seen in follow-up appointments and for how long?
Participants in Group A will be given the clinical trial treatment cevostamab for a maximum of 13 cycles. Some participants may be eligible for additional cycles of cevostamab treatment (known as re-treatment) if they meet certain criteria.
Participants in Groups B and C will be given cevostamab together with either pomalidomide/dexamethasone or daratumumab/dexamethasone. You may continue to receive treatment until your disease worsens or until you experience unmanageable side effects due to the clinical trial treatment (dexamethasone may be stopped earlier). You are free to stop the clinical trial treatment at any time. After stopping treatment, you will still be seen regularly by the clinical trial doctor roughly every 3 months. These hospital visits will include physical check-ups and blood tests to see how you have responded to treatment.
5. What happens if I am unable to take part in this clinical trial?
If this clinical trial is not suitable for you, you will not be able to take part. Your doctor will suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular medical care.
For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov
Trial-identifier: NCT04910568
Trial Summary
This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab monotherapy, cevostamab plus pomalidomide and dexamethasone (Pd) or cevostamab plus daratumumab and dexamethasone (Dd) which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.
Genentech, Inc.
Sponsor
Phase 1
Phase
NCT04910568,GO42552,2021-000238-33
Trial Identifier
Cevostamab, Tocilizumab, Pomalidomide, Daratumumab, Dexamethasone
Treatments
Multiple Myeloma
Condition
Official Title
An open-label, multicenter, phase Ib trial evaluating the safety, pharmacokinetics, and activity of cevostamab as monotherapy and cevostamab plus pomalidomide and dexamethasone or cevostamab plus daratumumab and dexamethasone in patients with relapsed or refractory multiple myeloma
Eligibility Criteria
All
Gender
≥18 Years
Age
No
Healthy Volunteers
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy of at least 12 weeks
- Agreement to provide bone marrow biopsy and aspirate samples
- Resolution of adverse events from prior anti-cancer therapy to Grade <=1
- Measurable disease
- For women of childbearing potential: agreement to remain abstinent or use contraception, during the treatment period (including treatment interruptions) and for at least 5 months after the last dose of cevostamab and at least 3 months after the last dose of tocilizumab was administered
- For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, during the treatment period, and for at least 2 months after the last dose of tocilizumab was administered to avoid exposing the embryo and sexual partner Additional Arm A-Specific Inclusion Criteria
- Diagnosis of R/R MM for which no established therapy for MM is appropriate and available, or intolerance to those established therapies Additional Arm B-Specific Inclusion Criteria
- For Cohort B1S: Participants with R/R MM who have received at least two prior lines of treatment
- For Cohort B2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of treatment
- Agreement to comply with all requirements of the pomalidomide pregnancy prevention program
- For women of childbearing potential: agreement to remain abstinent or use two reliable methods of contraception starting at least 4 weeks prior to, during the treatment period, and for at least 4 weeks after the last dose of pomalidomide was administered
- For men: agreement to remain abstinent or use a condom during the treatment period and for at least 4 weeks after the last dose of pomalidomide, (even if he has undergone a successful vasectomy) and agreement to refrain from donating sperm and blood during this same period Additional Arm C-Specific Inclusion Criteria
- For Cohort C1S: Participants with R/R MM who have received at least two prior lines of treatment
- For Cohort C2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of therapy
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods during the treatment period and for at least 102 days after the last dose of daratumumab was administered
- For men: agreement to remain abstinent or use a condom during the treatment period and for at least 102 days after the last dose of daratumumab was administered to avoid exposing the embryo, and agreement to refrain from donating sperm during this same period
Exclusion Criteria
- Prior treatment with cevostamab or another agent targeting FcRH5
- Inability to comply with protocol-mandated hospitalization and activities restrictions
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of tocilizumab (if applicable).
- Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drugconjugate as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy
- Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study treatment
- Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12 weeks before first study treatment
- Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
- Treatment with any chemotherapeutic agent or other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment
- Autologous SCT within 100 days prior to first study treatment
- Prior allogeneic stem cell transplant(ation) (SCT)
- Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
- Prior solid organ transplantation
- History of autoimmune disease
- History of confirmed progressive multifocal leukoencephalopathy
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- Known history of amyloidosis
- Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
- History of other malignancy within 2 years prior to screening
- Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
- Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
- Significant cardiovascular disease
- Symptomatic active pulmonary disease or requiring supplemental oxygen
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
- Known or suspected chronic active Epstein-Barr virus (EBV) infection
- Recent major surgery within 4 weeks prior to first study treatment
- Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
- Acute or chronic hepatitis C virus (HCV) infection
- Known history of Grade >= 3 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
- Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
- Active symptomatic coronavirus disease 2019 (COVID-19) infection at study enrollment or requiring treatment with intravenous (IV) antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Patients with active COVID-19 infection must have clinical recovery and two negative antigen tests at least 24 hours apart prior to first study treatment
- Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus (CMV) PCR prior to first study treatment
- Known history of HIV seropositivity
- Administration of a live, attenuated vaccine within 4 weeks before first study treatment or anticipation that such a live attenuated vaccine will be required during the study
- Treatment with systemic immunosuppressive medications, with the exception of corticosteroid treatment <=10 mg/day prednisone or equivalent, within 2 weeks prior to first study treatment
- History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment Additional Arm B-Specific Exclusion Criteria
- Pregnant or breastfeeding, or intending to become pregnant 4 weeks prior to initiation of study treatment, during the study, (including treatment interruptions) or within 4 weeks after the last dose of pomalidomide
- Significant cardiovascular disease (such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 12 months, uncontrolled arrhythmias, or unstable angina)
- History of erythema multiforme, Grade >=3 rash, blistering, or severe hypersensitivity to prior treatment with immunomodulatory drugs such as thalidomide, lenalidomide, or pomalidomide
- Inability to tolerate thromboprophylaxis, or contraindication to thromboprophylaxis
- GI disease that might significantly alter absorption of oral drugs Additional Arm C-Specific Exclusion Criteria
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 102 days after the last dose of daratumumab
- Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of daratumumab formulations
- Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
- Known moderate or severe persistent asthma within the past 2 years, or current uncontrolled asthma of any classification
For the latest version of this information please go to www.forpatients.roche.com