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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03275103
Collaborator
(none)
300
Enrollment
18
Locations
7
Arms
59.4
Anticipated Duration (Months)
16.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 19, 2017
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Aug 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A: Single Step Dose Escalation for Cevostamab

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
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Names:
  • BFCR4350A; RO7187797
  • Experimental: Arm B: Multistep Dose Escalation for Cevostamab

    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
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other Names:
  • BFCR4350A; RO7187797
  • Experimental: Arm C: Single Step Dose Expansion for Cevostamab

    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
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other Names:
  • BFCR4350A; RO7187797
  • Experimental: Arm D: Multistep Dose Expansion for Cevostamab

    The multistep dose expansion stage of the study may use the dosing and assessment schedule from the multistep dose escalation arm in Cycle 1, based on data from Arm B.

    Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other Names:
  • BFCR4350A; RO7187797
  • Experimental: Arm E: Expansion Phase for Tocilizumab Pretreatment

    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: Tocilizumab
    Tocilizumab will be administered as premedication during Cycle 1.
    Other Names:
  • Actemra/RoActemra
  • Experimental: Arm F: Single Step Dose Expansion for Cevostamab

    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
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other Names:
  • BFCR4350A; RO7187797
  • Experimental: Arm G: Multistep Dose Expansion for Cevostamab

    The multistep dose expansion stage of the study may use the dosing and assessment schedule from the multistep dose escalation arm in Cycle 1, based on data from Arm B.

    Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other Names:
  • BFCR4350A; RO7187797
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants with Adverse Events (AEs) [Up to approximately 5 years]

      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.

    2. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Up to approximately 5 years]

      Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), except for Cytokine release syndrome (CRS), which will be graded according to the Modified Cytokine Release Syndrome Grading System.

    3. Arm E Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab [Up to approximately 5 years]

      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.

    Secondary Outcome Measures

    1. Area Under the Concentration-Time Curve [Up to approximately 5 years]

      Defined as the total exposure of study drug.

    2. Cmax [Up to approximately 5 years]

      Defined as the maximum observed serum concentration of study drug.

    3. Minimum observed serum concentration (Cmin) [Up to approximately 5 years]

      Defined as the minimum observed serum concentration of study drug.

    4. Clearance (CL) [Up to approximately 5 years]

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

    5. Volume of Distribution at Steady State (Vdss) [Up to approximately 5 years]

      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.

    6. Objective Response Rate (ORR) [Up to approximately 5 years]

      OR is defined as percentage of participants with partial response (PR) or complete response (CR). 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 bone marrow (BM). PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 milligrams (mg)/24 hours.

    7. Duration of Response [Up to approximately 5 years]

      Time from first occurrence of OR (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.

    8. Change from Baseline in the Presence Anti-Drug Antibodies (ADAs) [Up to approximately 5 years]

      To evaluate the immune response to the study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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 3 months after last dose of study drug

    • Male participants must agree to refrain from donating sperm, to abstain or use a condom during the treatment period, and at least 60 days after last dose of study drug

    Exclusion Criteria:
    • Inability to comply with protocol-mandated hospitalization and activities restrictions

    • Pregnant, lactating, or planning to become pregnant during the study and up to 3 months after last dose of study drug

    • 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

    • 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

    • Known or suspected chronic active Epstein-Barr virus (EBV) infection, acute or chronic hepatitis C virus (HCV) infection

    • Positive serologic or polymerase chain reaction (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

    • 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35249
    2Mayo Clinic Hospital - ArizonaScottsdaleArizonaUnited States85259
    3City of HopeDuarteCaliforniaUnited States91010
    4University of California San FranciscoSan FranciscoCaliforniaUnited States94117
    5University of Colorado DenverAuroraColoradoUnited States80045
    6Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
    7Memorial Sloan KetteringNew YorkNew YorkUnited States10065
    8Mount Sinai HospitalNew YorkNew YorkUnited States10128
    9University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
    10Sarah Cannon Research InstituteNashvilleTennesseeUnited States37203
    11The University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030-4009
    12Peter MacCallum Cancer CenterEast MelbourneVictoriaAustralia3002
    13Alfred HospitalMelbourneVictoriaAustralia3004
    14University of CalgaryCalgaryAlbertaCanadaT2N 2T9
    15Princess Margaret Cancer CenterTorontoOntarioCanadaM5G 1Z5
    16Jewish General HospitalMontrealQuebecCanadaH3T 1E2
    17Clinica Universidad de NavarraPamplonaNavarraSpain31008
    18Hospital Clinico Universitario de Salamanca; Servicio de OncologiaSalamancaSpain37007

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT03275103
    Other Study ID Numbers:
    • GO39775
    • 2018-001041-13
    First Posted:
    Sep 7, 2017
    Last Update Posted:
    Nov 17, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 17, 2021