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

Study Purpose

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.

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:

  • - 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.
  • - For Cohort B1E and additional cohorts: Participants with R/R MM who have received at least 1 prior line of treatment.
  • - 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: Participants with R/R MM who have received at least two prior lines of treatment.
  • - For Cohort C1E 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 chimeric antigen receptor T (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 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

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.

NCT04910568
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
Lead Sponsor

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

Genentech, Inc.
Principal Investigator

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

Clinical Trials
Principal Investigator Affiliation Genentech, Inc.
Agency Class

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

Industry
Overall Status Recruiting
Countries Australia, Canada, Czechia, United States
Conditions

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

Multiple Myeloma
Arms & Interventions

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. Upon completion, Cohort A1E, an expansion cohort may be opened. 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 15-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. Upon completion, 2 expansion cohorts will be opened at dose level 1 (Cohort B1E) and at dose level 2 (Cohort B2E). They 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. Upon completion, 2 expansion cohorts will be opened at dose level 1 (Cohort C1E) and at dose level 2 (Cohort C2E). They will follow the same Q3W/Q4W dosing schedule as Cohort C1S.

Interventions

Drug: - 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 Arms B and C, participants can be treated until disease progression or unacceptable toxicity.

Drug: - Tocilizumab

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

Drug: - Pomalidomide

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

Drug: - Daratumumab

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

Drug: - 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.

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.

City of Hope, Duarte, California

Status

Recruiting

Address

City of Hope

Duarte, California, 91010

Denver, Colorado

Status

Active, not recruiting

Address

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

Denver, Colorado, 80218

Karmanos Cancer Institute., Detroit, Michigan

Status

Recruiting

Address

Karmanos Cancer Institute.

Detroit, Michigan, 48201

Washington University School of Medicine, Saint Louis, Missouri

Status

Active, not recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

International Sites

Melbourne, Victoria, Australia

Status

Recruiting

Address

Peter MacCallum Cancer Centre; Department of Haematology

Melbourne, Victoria, 3002

Melbourne, Victoria, Australia

Status

Recruiting

Address

The Alfred Hospital; Malignant Haematology & Stem Cell Transplant Service

Melbourne, Victoria, 3004

Toronto, Ontario, Canada

Status

Recruiting

Address

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9

Ostrava, Czechia

Status

Recruiting

Address

Fakultni Nemocnice Ostrava; Klinika hematoonkologie FNO a LF OU

Ostrava, , 708 52