A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma

Study Purpose

This study will evaluate the efficacy, safety, and pharmacokinetics of cevostamab in participants with refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Documented diagnosis of MM based on standard International Myeloma Working Group (IMWG) criteria.
  • - Evidence of progressive disease based on investigators determination of response by IMWG criteria on or after their last dosing regimen.
  • - Prior BCMA ADC or CAR-T Cohort: participants who have received a BCMA-targeted CAR-T or ADC therapy and are triple-class refractory.
  • - Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting T-cell-dependent bispecific (TDB) antibody and are triple-class refractory.
  • - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • - Life expectancy is at least 12 weeks.
  • - Agreement to protocol-specified assessments, including bone marrow biopsy and aspirate samples as detailed in the protocol.
  • - Resolution of AEs from prior anti-cancer therapy to Grade =< 1.
  • - For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 2 months after the final dose of cevostamab and for 3 months after the last dose of tocilizumab was administered.
  • - For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 2 months after the final dose of cevostamab or tocilizumab (if applicable) to avoid exposing the embryo.

Exclusion Criteria:

  • - Inability to comply with protocol-mandated hospitalization.
  • - Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of cevostamab or tocilizumab.
  • - Prior treatment with cevostamab or another agent with the same target.
  • - Prior BCMA ADC or CAR-T Cohort: prior treatment with any TDB antibody.
  • - Prior use of any monoclonal antibody (mAb), radioimmunoconjugate, or ADC 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- Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), anti- Programmed cell death protein 1 (PD-1), and anti- Programmed death-ligand 1 (PD-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 cevostamab infusion.
  • - Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors.
  • - Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment.
  • - Autologous stem cell transplantation (SCT) within 100 days prior to first study treatment.
  • - Prior allogeneic SCT.
  • - Circulating plasma cell count exceeding 500/ microliter (µL) 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 mAb 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, except those with negligible risk of metastasis or death, such as ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer not requiring treatment or appropriately treated Stage I uterine cancer.
  • - 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 that may limit a potential participant's ability to adequately respond to a cytokine release syndrome (CRS) event.
  • - Symptomatic active pulmonary disease or requiring supplemental oxygen.
  • - • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV (intravenous) antibiotics or antivirals for coronavirus disease 2019 (COVID-19) where the last dose of treatment was given within 14 days prior to first study treatment.
  • - Known or suspected chronic active Epstein-Barr virus (EBV) infection.
  • - Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) - Recent major surgery within 4 weeks prior to first study treatment.
  • - Positive serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection.
  • - Acute or chronic hepatitis C virus (HCV) infection.
  • - Known history of human immunodeficiency virus (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.
- Any medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05535244
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hoffmann-La Roche
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Clinical Trials
Principal Investigator Affiliation Hoffmann-La Roche
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

Experimental: Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T)

Participants in Cohort A1 will be treated at the double step-up split dosing regimen.

Experimental: Cohort A2: Prior BCMA Bispecific

Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1.

Experimental: Cohort B1: Prior BCMA ADC or CAR-T

Participants enrolled in expansion Cohort B1, will be given cevostamab at the recommended Phase 2 dose (RP2D).

Experimental: Cohort B2: Prior BCMA Bispecific

Expansion Cohort B2 will be opened, after the intiial results from Cohort A2, at the same dose as per Cohort B1.

Interventions

Drug: - Cevostamab

Cevostamab will be administered by IV infusion in 21-day cycles.

Drug: - Tocilizumab

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Tennessee Onc., PLLC - SCRI, Nashville, Tennessee

Status

Recruiting

Address

Tennessee Onc., PLLC - SCRI

Nashville, Tennessee, 37203