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

NCT03275103 | Completed Phase 1 FDA Drug

• 3 other identifiers: GO397752018-001041-132022-502053-34-00
• Study Type: interventional
• Target: 355
• Locations: 4 countries
• Sites: 17

Brief 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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to approximately 8 years

• 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.

  Up to approximately 8 years

• 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.

  Up to approximately 8 years

Secondary Outcomes (15)

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

  Up to approximately 8 years

• AUC of Tocilizumab

  Up to approximately 8 years

• Maximum Observed Serum Concentration (Cmax) of Cevostamab

  Up to approximately 8 years

• Cmax of Tocilizumab

  Up to approximately 8 years

• Minimum Observed Serum Concentration (Cmin) of Cevostamab

  Up to approximately 8 years

Study Arms (11)

Arm A: Single Step Dose Escalation for Cevostamab

EXPERIMENTAL

Study 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.

Drug: Cevostamab

Arm B: Double Step Dose Escalation for Cevostamab

EXPERIMENTAL

In 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.

Drug: Cevostamab

Arm C: Single Step Dose Expansion for Cevostamab

EXPERIMENTAL

The 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.

Drug: Cevostamab

Arm D: Double Step Dose Expansion for Cevostamab

EXPERIMENTAL

The 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.

Drug: Cevostamab

Arm E: Expansion Phase for Tocilizumab Pretreatment

EXPERIMENTAL

All 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.

Drug: Cevostamab; Drug: Tocilizumab

Arm F: Single Step Dose Expansion for Cevostamab

EXPERIMENTAL

The 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.

Drug: Cevostamab

Arm G: Double Step Dose Expansion for Cevostamab

EXPERIMENTAL

The 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.

Drug: Cevostamab

Arm H: Triple Step Dose Escalation for Cevostamab

EXPERIMENTAL

In 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.

Drug: Cevostamab

Arm I: Triple Step Dose Expansion for Cevostamab

EXPERIMENTAL

The 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.

Drug: Cevostamab

Arm J: Expansion Phase for Tocilizumab Pretreatment

EXPERIMENTAL

All 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.

Drug: Cevostamab; Drug: Tocilizumab

Arm K: Compressed Double Step Dose Expansion for Cevostamab

EXPERIMENTAL

In 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.

Drug: Cevostamab

Interventions

Cevostamab DRUG

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

Also known as: BFCR4350A; RO7187797

Arm A: Single Step Dose Escalation for Cevostamab; Arm B: Double Step Dose Escalation for Cevostamab; Arm C: Single Step Dose Expansion for Cevostamab; Arm D: Double Step Dose Expansion for Cevostamab; Arm E: Expansion Phase for Tocilizumab Pretreatment; Arm F: Single Step Dose Expansion for Cevostamab; Arm G: Double Step Dose Expansion for Cevostamab; Arm H: Triple Step Dose Escalation for Cevostamab; Arm I: Triple Step Dose Expansion for Cevostamab; Arm J: Expansion Phase for Tocilizumab Pretreatment; Arm K: Compressed Double Step Dose Expansion for Cevostamab

Tocilizumab DRUG

Tocilizumab will be administered as premedication during Cycle 1.

Also known as: Actemra/RoActemra

Arm E: Expansion Phase for Tocilizumab Pretreatment; Arm J: Expansion Phase for Tocilizumab Pretreatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Mayo Clinic Hospital - Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Mount Sinai Hospital

New York, New York, 10128, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Peter MacCallum Cancer Center

East Melbourne, Victoria, 3022, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

University of Calgary Cumming School of Medicine

Calgary, Alberta, T2N 4N2, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Clinica Universidad de Navarra

Pamplona/iruña, Navarre, 31008, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: September 19, 2017
• Primary Completion: January 7, 2026
• Study Completion: January 7, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); AU (2); CA (3); ES (2)