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NCT04910568PHASE1Recruiting

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

Genentech, Inc.

Start Date

7/26/2021

Completion Date

12/21/2028

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) * For Cohort B2S, B1E, B3E: Participants with R/R MM who have received at least one prior line of treatment that included at least two consecutive cycles of treatment, including a PI and an IMiD * For Cohort B4E: Participants with R/R MM who have received one to four lines of prior therapy that included at least two consecutive cycles of anti-CD38 therapy, lenalidomide and a PI, and either: Prior B-cell maturation antigen- (BCMA)-targeted therapy-directed chimeric antigen receptor T (CAR T) cell therapy or Prior BCMA-antibody-drug conjugate (ADC) therapy * 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: Patients with R/R MM who have received at least two prior lines of treatment including a PI and an IMiD * For Cohort C2S 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 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 hemophagocytic lymphohistiocytosis (HLH) or immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (IEC HS) * Active symptomatic coronavirus disease 2019 (COVID-19) infection at study enrollment or requiring treatment with intravenous (IV) antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Patients with active COVID-19 infection must have clinical recovery and two negative antigen tests at least 24 hours apart prior to first study treatment * Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus (CMV) PCR prior to first study treatment * 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

Interventions

DRUG

Cevostamab

DRUG

Tocilizumab

DRUG

Pomalidomide

DRUG

Daratumumab

DRUG

Dexamethasone

Interested in This Trial?

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Conditions

Multiple Myeloma

Locations

City of Hope

Duarte, California 91010

United States

City of Hope - Lennar Foundation Cancer Center

Irvine, California 92618

United States

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

Denver, Colorado 80218

United States

Winship Cancer Institute

Atlanta, Georgia 30322

United States

Karmanos Cancer Institute.

Detroit, Michigan 48201

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Peter MacCallum Cancer Centre

Melbourne, Victoria 3002

Australia

The Alfred Hospital

Melbourne, Victoria 3004

Australia

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

Hamilton Health Sciences

Hamilton, Ontario L8V 5C2

Canada

University Health Network

Toronto, Ontario M5G 2M9

Canada

Fakultni Nemocnice Ostrava

Ostrava, 708 52

Czechia

I Interni klinika

Prague, 128 08

Czechia

Rigshospitalet

København Ø, 2100

Denmark

Hôpital Saint-Louis

Paris, 75475

France

CHU de Poitiers - La Miletrie

Poitiers, 86021

France

CHU Pontchaillou

Rennes, 35003

France

Rambam Medical Center

Haifa, 3109601

Israel

Sourasky Medical Centre

Tel Aviv, 6423906

Israel

Asst Papa Giovanni Xxiii

Bergamo, Lombardy 24127

Italy

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy 25123

Italy

Nagoya City University Hospital

Aichi, 467-8602

Japan

National Hospital Organization Okayama Medical Center

Okayama, 701-1192

Japan

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550

Japan

Yamagata University Hospital

Yamagata, 990-9585

Japan

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214

Poland

Pratia Onkologia Katowice

Katowice, 41-500

Poland

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-569

Poland

Seoul National University Hospital

Seoul, 03080

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital General Universitario Gregorio Marañon

Madrid, 28009

Spain

University College London Hospitals NHS Foundation Trust

London, W1T 7HA

United Kingdom

Royal Marsden Hospital

Sutton, SW3 6JJ

United Kingdom