A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (CAMMA 1)

*The trial information contained on this page was imported from ClinicalTrials.gov. Click here to view this trial on ClinicalTrials.gov.

Back to search
Print this study
Full 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
Myeloma stage or condition:
Multiple Myeloma
Study phase:
Phase 1
Summary/Purpose:
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.
Detailed Description:
Not available
Treatments:
Drug : Cevostamab

Cevostamab will be administered intravenously on a 28-day cycle, up to a total of 13 cycles (Arm A), in 28-day cycles Q2W followed by Q4W (Arm B) and in 21 day cycles from C1-C8 Q3W and 28-day cycles from C9 onwards Q4W (Arm C). For Arm A, participants have the option to enter re-treatment after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.

Drug : Tocilizumab

Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Drug : Pomalidomide

Pomalidomide will be administered orally (PO) on a 28-day cycle.

Drug : Daratumumab

Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).

Drug : Dexamethasone

Arm A: Dexamethasone will be administered as a premedication. Arms B and C: Dexamethasone will be administered via IV or orally at 20 mg as study investigational medicinal product.

Study Arms:
Experimental : Single-Agent Cevostamab (Arm A)
Cohort A1S is a safety run-in arm evaluating cevostamab administered in 28-day cycles on a modified weekly schedule. Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule.
Experimental : Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B)
Participants will be treated with cevostamab monotherapy during a 14-day period prior to the start of pomalidomide treatment (cevostamab pre-phase). Cohort B1S is a safety run-in arm evaluating cevostamab and Pd administered in 28-day cycles every 2 weeks (Q2W) followed by every 4 weeks (Q4W) schedule. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S.
Experimental : Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C)
Cohort C1S is a safety run-in arm evaluating cevostamab and Dd administered in 21 day cycles from Cycle(C)1 - C8 every 3 weeks (Q3W) and 28-day cycles from C9 onwards Q4W. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S.
Study Type:
Interventional
Study Design:
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)
Recruitment status:
Recruiting
Eligibility criteria:
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
Locations / Centres:

Hamilton Health Sciences, Hamilton, Ontario – Recruiting

University Health Network; Princess Margaret Hospital; Medical Oncology Dept, Toronto, Ontario – Recruiting

Contacts:
Name: Reference Study ID Number: GO42552 https://forpatients.roche.com/
Phone: 888-662-6728 (U.S. and Canada)
Email: [email protected]
Publications:
???
First posted:
2021-06-02
Actual start date:
July 26, 2021
Last updated:
2024-04-03
Estimated enrollment:
184
Estimated completion date:
2025-07-15
Estimated primary completion date:
2024-09-11
Condition:
Multiple Myeloma
Gender:
All
Ages:
18 Years-N/A
Accepts healthy volunteers:
No
Listed location countries:
Australia
Canada
Czechia
Denmark
France
Israel
Italy
Korea, Republic of
Poland
Spain
United Kingdom
United States
NCT number:
NCT04910568
Other study ID numbers:
GO42552
Has Data monitoring committee:
No
U.S. FDA-regulated product:
Yes
IPD Sharing Statement :
???
Responsible party:
Sponsor
Study sponsor:
collaborator
Hoffmann-La Roche
Industry
lead_sponsor
Genentech, Inc.
Industry
Collaborators:
???
Investigators:
Clinical Trials Genentech, Inc.
Protocol Registration and Results System:
???
Verification date:
2024-04-01