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Multiple MyelomaPhase 1NCT03275103

Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)

A Phase 1 study testing Cevostamab and Tocilizumab in people with Multiple Myeloma, run by Genentech, Inc. at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Cevostamab and Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
355 participants
Where
17 sitesin 4 countries
Study dates
19 Sep 2017to 7 Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy of at least 12 weeks
  • Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which no established therapy for MM is appropriate and available or be intolerant to those established therapies
  • Adverse events from prior anti-cancer therapy resolved to Grade < or = 1, except any grade alopecia and/or peripheral sensory or motor neuropathy which must have resolved to Grade < or = 2
  • Measurable disease defined by laboratory test results
  • Female participants of childbearing age must agree to remain abstinent or use reliable contraceptive methods during the treatment period, and at least 5 months after last dose of study drug. Women must refrain from breastfeeding during the same period.
  • Male participants must agree to refrain from donating sperm, to abstain or use a condom during the treatment period, and for at least 2 months after the last dose of tocilizumab (if applicable).

Who cannot join

  • Inability to comply with protocol-mandated hospitalization and activities restrictions
  • Pregnant or breastfeeding, or planning 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 of tocilizumab (if applicable)
  • Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate as anti-cancer therapy within 4 weeks before first infusion
  • Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first infusion
  • Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks before first cevostamab infusion
  • Known treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents
Show all 30Show fewer
  • Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first cevostamab infusion
  • Autologous stem cell transplantation (SCT) within 100 days prior to first infusion
  • Prior allogeneic SCT or solid organ transplantation
  • Absolute plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
  • History of autoimmune disease or of confirmed progressive multifocal leukoencephalopathy
  • Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • Patients with known history of amyloidosis (e.g., positive Congo Red stain or equivalent in tissue biopsy)
  • Patients with lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
  • History of other malignancy that could affect compliance with the protocol or interpretation of results
  • Current or past history of central nervous system (CNS) disease, or CNS involvement by MM
  • Significant cardiovascular disease that may limit a patient's ability to adequately respond to a CRS event
  • Symptomatic active pulmonary disease requiring supplemental oxygen
  • Within 14 days prior to first cevostamab infusion: known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks prior to first infusion
  • Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR) or cytomegalovirus (CMV) PCR prior to first study treatment
  • Known or suspected chronic active EBV infection, acute or chronic hepatitis C virus (HCV) infection
  • Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
  • Recent major surgery within 4 weeks prior to first infusion
  • Human Immunodeficiency Virus (HIV) positive
  • Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment
  • Administration of a live, attenuated vaccine within 4 weeks before first cevostamab infusion or anticipation that such a live attenuated vaccine will be required during the study
  • Received systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment <=10 mg/day prednisone or equivalent within 2 weeks prior to first dose of cevostamab and, if applicable, tocilizumab premedication prior to first dose of cevostamab
  • History of illicit drug or alcohol abuse within 12 months prior to screening
  • Any medical condition or laboratory test abnormality that precludes the participant's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Trial locations and contacts

17 sites in 4 countries.

17 sites in 4 countries

United States10 sites

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope

    Duarte, California, 91010

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Tennessee Oncology - Nashville

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering

    New York, New York, 10065

  • Mount Sinai Hospital

    New York, New York, 10128

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Hospital - Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

Canada3 sites

  • University of Calgary Cumming School of Medicine

    Calgary, Alberta, T2N 4N2

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Australia2 sites

  • Peter MacCallum Cancer Center

    East Melbourne, Victoria, 3022

  • Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

Spain2 sites

  • Clinica Universidad de Navarra

    Pamplona/iruña, Navarre, 31008

  • Hospital Clinico Universitario de Salamanca

    Salamanca, 37007

Other trials in Spain

About this study

Official title: An Open-Label, Multicenter, Phase I Trial Evaluating the Safety and Pharmacokinetics of Escalating Doses of Cevostamab (BFCR4350A) in Patients With Relapsed or Refractory Multiple Myeloma

This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).

Being tested
Cevostamab, Tocilizumab
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CevostamabDrug

    Also called BFCR4350A; RO7187797

    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.

  • TocilizumabDrug

    Also called Actemra/RoActemra

    Tocilizumab will be administered as premedication during Cycle 1.

Study groups in NCT03275103
Study groupRoleWhat they receive
Arm A: Single Step Dose Escalation for CevostamabExperimentalStudy drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
Receives: Drug: Cevostamab
Arm B: Double Step Dose Escalation for CevostamabExperimentalIn Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
Receives: Drug: Cevostamab
Arm C: Single Step Dose Expansion for CevostamabExperimentalThe single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.
Receives: Drug: Cevostamab
Arm D: Double Step Dose Expansion for CevostamabExperimentalThe double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.
Receives: Drug: Cevostamab
Arm E: Expansion Phase for Tocilizumab PretreatmentExperimentalAll participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.
Receives: Drug: Cevostamab; Drug: Tocilizumab
Arm F: Single Step Dose Expansion for CevostamabExperimentalThe single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.
Receives: Drug: Cevostamab
Arm G: Double Step Dose Expansion for CevostamabExperimentalThe double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.
Receives: Drug: Cevostamab
Arm H: Triple Step Dose Escalation for CevostamabExperimentalIn Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
Receives: Drug: Cevostamab
Arm I: Triple Step Dose Expansion for CevostamabExperimentalThe triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H.
Receives: Drug: Cevostamab
Arm J: Expansion Phase for Tocilizumab PretreatmentExperimentalAll participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.
Receives: Drug: Cevostamab; Drug: Tocilizumab
Arm K: Compressed Double Step Dose Expansion for CevostamabExperimentalIn Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
Receives: Drug: Cevostamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events (AEs)

    An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

    Measured: Up to approximately 8 years

  2. Percentage of Participants With Dose-Limiting Toxicities (DLTs)

    Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.

    Measured: Up to approximately 8 years

  3. Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab

    Cytokine release syndrome was recorded as an AE that generally occurs >30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.

    Measured: Up to approximately 8 years

Secondary outcomes (15)

  1. Area Under the Concentration-Time Curve (AUC) of Cevostamab

    Defined as the total exposure of study drug.

    Measured: Up to approximately 8 years

  2. AUC of Tocilizumab

    Defined as the total exposure of study drug.

    Measured: Up to approximately 8 years

  3. Maximum Observed Serum Concentration (Cmax) of Cevostamab

    Defined as the maximum observed serum concentration of study drug.

    Measured: Up to approximately 8 years

  4. Cmax of Tocilizumab

    Defined as the maximum observed serum concentration of study drug.

    Measured: Up to approximately 8 years

  5. Minimum Observed Serum Concentration (Cmin) of Cevostamab

    Defined as the minimum observed serum concentration of study drug.

    Measured: Up to approximately 8 years

  6. Cmin of Tocilizumab

    Defined as the minimum observed serum concentration of study drug.

    Measured: Up to approximately 8 years

  7. Clearance (CL) of Cevostamab

    Defined as the volume of plasma cleared of the drug per unit time.

    Measured: Up to approximately 8 years

  8. CL of Tocilizumab

    Defined as the volume of plasma cleared of the drug per unit time.

    Measured: Up to approximately 8 years

  9. Volume of Distribution at Steady State (Vdss) of Cevostamab

    Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

    Measured: Up to approximately 8 years

  10. Vdss of Tocilizumab

    Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

    Measured: Up to approximately 8 years

  11. Serum Concentration of Cevostamab

    Measured: Up to approximately 8 years

  12. Serum Concentration of Tocilizumab

    Measured: Up to approximately 8 years

  13. Objective Response Rate (ORR)

    ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) .

    sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio </=4:1 or >/=1:2 for kappa and lambda participants, respectively after counting >/=100 plasma cells).

    CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and </= 5% plasma cells in BM.

    VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 milligrams (mg)/24 hr.

    PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 mg/24 hours.

    Measured: Up to approximately 8 years

  14. Duration of Response

    Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of >/=25% from lowest response value in one of the following: serum M-protein (absolute increase >/=0.5 grams per deciliter (g/dL); serum M-protein increase >/=1g/dL, if lowest M component was >/=5g/dL; urine M-protein (absolute increase >/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % >/=10%); new lesion(s) >/=50% increase from lowest point in sum of the products of diameters of > 1 lesion, or >/=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.

    Measured: Up to approximately 8 years

  15. Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)

    To evaluate the immune response to the study drug.

    Measured: Up to approximately 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2017
  2. Study start19 Sep 2017
  3. Primary completion7 Jan 2026
  4. Study completion7 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
355 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03275103
Sponsor's protocol ID
GO39775
Other IDs
2018-001041-13, 2022-502053-34-00, 2018
Status last verified
Feb 2026
First submitted
5 Sep 2017
Last updated
5 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cohen AD, Richter J, Trudel S, Lesokhin A, Laubach JP, Thomas SK, Harrison SJ, Costa LJ, Spencer A, Fonseca R, Forsberg PA, Berdeja JG, Kaedbey R, Bahlis NJ, Rodriguez-Otero P, Mateos MV, Tyagi T, Samineni D, Liu W, Nakamura R, Choeurng V, Wong C, Cooper J, Krishnan A. FcRH5xCD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial. Nat Med. 2026 Aug;32(8):2909-2917. doi: 10.1038/s41591-026-04522-3. Epub 2026 Jul 22.

    PubMed 42487061

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cevostamab and Tocilizumab in people with Multiple Myeloma, run by Genentech, Inc. at 17 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada, Australia, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (AEs) (time frame: Up to approximately 8 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03275103, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.

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