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A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (CAMMA 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04910568
Recruitment Status : Recruiting
First Posted : June 2, 2021
Last Update Posted : June 22, 2022
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Cevostamab Drug: Tocilizumab Drug: Pomalidomide Drug: Daratumumab Drug: Dexamethasone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : July 26, 2021
Estimated Primary Completion Date : July 14, 2023
Estimated Study Completion Date : December 5, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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.

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.
Other Name: Actemra/RoActemra

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.


Experimental: Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B)

Participants will be treated with cevostamab monotherapy during a 21-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, Cohort B1E, an expansion cohort may be opened. It will follow the same Q2W/Q4W dosing schedule as Cohort B1S.

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.
Other Name: Actemra/RoActemra

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

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.


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, Cohort C1E, an expansion cohort may be opened. It will follow the same Q3W/Q4W dosing schedule as Cohort C1S.

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.
Other Name: Actemra/RoActemra

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.





Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 3 years ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 3 years ]
  2. Complete Response/Stringent Complete Response (CR/sCR) Rate [ Time Frame: Baseline up to approximately 3 years ]
  3. Rate of Very Good Partial Response (VGPR) or Better [ Time Frame: Baseline up to approximately 3 years ]
  4. Progression-free Survival (PFS) [ Time Frame: Start of study treatment to first date of disease progression or death from any cause, whichever occurs first (up to approximately 3 years) ]
  5. Duration of Response (DOR) [ Time Frame: From first partial response (PR) or better until the first date of disease progression or death from any cause, whichever occurs first (up to approximately 3 years) ]
  6. Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better) [ Time Frame: Baseline up to approximately 3 years ]
  7. Time to Best Response (for Participants who Achieve a Response of PR or Better) [ Time Frame: Baseline up to approximately 3 years ]
  8. Minimal Residual Disease (MRD) Negativity [ Time Frame: Baseline up to approximately 3 years ]
  9. Overall Survival (OS) [ Time Frame: Baseline up until death from any cause (up to approximately 3 years) ]
  10. Serum Concentration of Cevostamab at Specified Timepoints [ Time Frame: Cevostamab Pre-Phase (CPP) Day (D) 1 up to approximately 3 years ]
  11. Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab [ Time Frame: CPP D1 up to approximately 3 years ]
  12. Maximum Observed Serum Concentration (Cmax) of Cevostamab [ Time Frame: CPP D1 up to approximately 3 years ]
  13. Minimum Observed Serum Concentration (Cmin) of Cevostamab [ Time Frame: CPP D1 up to approximately 3 years ]
  14. Clearance of Cevostamab [ Time Frame: CPP D1 up to approximately 3 years ]
  15. Volume of Distribution at Steady State of Cevostamab [ Time Frame: CPP D1 up to approximately 3 years ]
  16. Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline [ Time Frame: Baseline ]
  17. Percentage of Participants with ADAs Against Cevostamab During the Study [ Time Frame: Up to approximately 3 years ]
  18. Serum Concentration of Pomalidomide [ Time Frame: From Cycle 1 Day 1 through Cycle 6 Day 15. Each cycle=28 days ]
  19. Serum Concentration of Daratumumab [ Time Frame: From C1D1 until disease progression or unexpected toxicity. Cycles 1-8 are 21 days and Cycle 9 onward are 28 days. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 2 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 cevostamab or 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: Patients with R/R MM who have received at least 2 prior lines of treatment
  • For Cohort B1E: Patients with R/R MM who have received at least 1 prior line of treatment
  • Agreement to comply with all local requirements of the pomalidomide pregnancy risk minimization plan
  • 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, and agreement to refrain from donating sperm during this same period Additional Arm C-Specific Inclusion Criteria
  • For Cohort C1S: Patients with R/R MM who have received at least 2 prior lines of treatment
  • For Cohort C1E: Patients 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 3 months 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 3 months 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 2 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, 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 3 months 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04910568


Contacts
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Contact: Reference Study ID Number: GO42552 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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United States, California
City of Hope Active, not recruiting
Duarte, California, United States, 91010
United States, Colorado
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center Active, not recruiting
Denver, Colorado, United States, 80218
United States, Michigan
Karmanos Cancer Institute. Recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine Active, not recruiting
Saint Louis, Missouri, United States, 63110
Australia, Victoria
Peter MacCallum Cancer Centre; Department of Haematology Active, not recruiting
Melbourne, Victoria, Australia, 3002
The Alfred Hospital; Malignant Haematology & Stem Cell Transplant Service Recruiting
Melbourne, Victoria, Australia, 3004
Canada, Ontario
University Health Network; Princess Margaret Hospital; Medical Oncology Dept Recruiting
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Genentech, Inc.
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Genentech, Inc.
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT04910568    
Other Study ID Numbers: GO42552
2021-000238-33 ( EudraCT Number )
First Posted: June 2, 2021    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Daratumumab
Pomalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors