Recruiting

Phase 1

Cevostamab, Pomalidomide, Dexamethasone, DaratumumabA Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor:

Genentech, Inc.

Code:

NCT04910568

Conditions

Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cevostamab

Tocilizumab

Pomalidomide

Daratumumab

Dexamethasone

Study Details

Brief 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.

Conditions

Multiple Myeloma

Study ID

NCT04910568

Start date

Jul 26, 2021

Status verified date

Aug, 2026

Completion date

Dec 21, 2028

Anticipated

Primary completion date

Dec 21, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
For Cohort B2S, B1E, B3E: Participants with R/R MM who have received at least one prior line of treatment that included at least two consecutive cycles of treatment, including a PI and an IMiD
For Cohort B4E: Participants with R/R MM who have received one to four lines of prior therapy that included at least two consecutive cycles of anti-CD38 therapy, lenalidomide and a PI, and either: Prior B-cell maturation antigen- (BCMA)-targeted therapy-directed chimeric antigen receptor T (CAR T) cell therapy or Prior BCMA-antibody-drug conjugate (ADC) therapy
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: Patients with R/R MM who have received at least two prior lines of treatment including a PI and an IMiD
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 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 immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (IEC HS)
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

Study Design

Enrollment

186 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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 (Cohorts B1E and B3E). An additional non-randomized expansion cohort (Cohort B4E) will be included. 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.

Interventions

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 within 12 months of the end of treatment visit. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.

Tocilizumab

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

Pomalidomide

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

Daratumumab

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

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.

Primary outcome measure

Recommended Phase II Dose (RP2D) [ Time Frame: Baseline up to approximately 4 years ]
Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 4 years ]
Percentage of Dose Interruptions [ Time Frame: Baseline up to approximately 4 years ]
Percentage of Dose Reductions [ Time Frame: Baseline up to approximately 4 years ]
Percentage of Dose Intensity [ Time Frame: Baseline up to approximately 4 years ]
Percentage of Treatment Discontinuation [ Time Frame: Baseline up to approximately 4 years ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: GO42552 https://forpatients.roche.com/No attachments to email below.

888-662-6728 (U.S. and Canada)global-roche-genentech-trials@gene.com

Locations

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Recruiting

Denver, Colorado, United States, 80218

More Information

Sponsor

Genentech, Inc.

Last update posted

Aug 20, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Genentech, Inc. on 2026-08-20.