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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05535244




Registration number
NCT05535244
Ethics application status
Date submitted
24/08/2022
Date registered
10/09/2022

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma
Scientific title
A Phase I/II, Open-Label, Multi-Cohort Study to Evaluate the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen-Exposed Patients With Relapsed/Refractory Multiple Myeloma
Secondary ID [1] 0 0
2021-006816-10
Secondary ID [2] 0 0
CO43476
Universal Trial Number (UTN)
Trial acronym
CAMMA 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cevostamab
Treatment: Drugs - Tocilizumab

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 CAR-T - Participants enrolled in expansion Cohort B1, will be given cevostamab at the selected dosing regimen.

Experimental: Cohort B2: Prior BCMA Bispecific - Expansion Cohort B2 will be opened, after the initial results from Cohort A2, at the same dose as per Cohort B1.


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

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) as Determined by the Investigator
Timepoint [1] 0 0
Baseline up to approximately 2 years
Primary outcome [2] 0 0
Percentage of Participants with Adverse Events
Timepoint [2] 0 0
Baseline up to approximately 2 years
Secondary outcome [1] 0 0
ORR as Determined by the Independent Review Committee (IRC)
Timepoint [1] 0 0
Baseline up to approximately 2 years
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Baseline up to approximately 2 years
Secondary outcome [3] 0 0
Rate of Complete Response (CR) or Better
Timepoint [3] 0 0
Baseline up to approximately 2 years
Secondary outcome [4] 0 0
Rate of Very Good Partial Response (VGPR) or Better
Timepoint [4] 0 0
Baseline up to approximately 2 years
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Baseline up until death from any cause (up to approximately 2 years)
Secondary outcome [6] 0 0
Progression-free Survival (PFS)
Timepoint [6] 0 0
Baseline up to approximately 2 years
Secondary outcome [7] 0 0
Time to First Response (for Participants who Achieve an Objective Response)
Timepoint [7] 0 0
Baseline up to approximately 2 years
Secondary outcome [8] 0 0
Time to Best Response (for Participants who Achieve an Objective Response)
Timepoint [8] 0 0
Baseline up to approximately 2 years
Secondary outcome [9] 0 0
Percentage of Participants Experiencing a Clinically Meaningful Improvement in the Fatigue Domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core-30 Questionnaire (QLQ-C30) and EORTC QLQ-MY20
Timepoint [9] 0 0
Baseline up to approximately 2 years
Secondary outcome [10] 0 0
Time to Deterioration in the Fatigue Domain of the EORTC QLQ-C30 and/or Disease Symptoms Domain of the EORTC QLQ-MY20
Timepoint [10] 0 0
Baseline up to approximately 2 years
Secondary outcome [11] 0 0
Serum Concentration of Cevostamab at Specified Timepoints
Timepoint [11] 0 0
At Cycles 1, 2, 3, 4, 6, 8 and every other cycle until the end of treatment up to approximately 2 years. Each cycle is 21-days.
Secondary outcome [12] 0 0
Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
Timepoint [12] 0 0
Baseline
Secondary outcome [13] 0 0
Percentage of Participants with ADAs Against Cevostamab During the Study
Timepoint [13] 0 0
Up to approximately 2 years
Secondary outcome [14] 0 0
Cytokine Release Syndrome (CRS) Following Administration of Tocilizumab
Timepoint [14] 0 0
Baseline up to approximately 2 years
Secondary outcome [15] 0 0
Relationship Between Serum Concentration of Cevostamab and Cytokine Release
Timepoint [15] 0 0
Baseline up to approximately 2 years
Secondary outcome [16] 0 0
Relationship Between Serum Concentration of Cevostamab and T Cell Number
Timepoint [16] 0 0
Baseline up to approximately 2 years
Secondary outcome [17] 0 0
Relationship Between Serum Concentration of Cevostamab and T-cell Activation State
Timepoint [17] 0 0
Baseline up to approximately 2 years

Eligibility
Key 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 relapsed or refractory
* Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting T-cell-dependent bispecific (TDB) antibody and are triple-class relapsed or 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 5 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 tocilizumab (if applicable) to avoid exposing the embryo
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability to comply with protocol-mandated hospitalization
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of cevostamab or tocilizumab or within 3 months after the last dose of tocilizumab (if applicable)
* Prior treatment with cevostamab or another agent with the same target
* Prior BCMA ADC or CAR-T Cohort: prior treatment with any T cell dependent bi-specific antibody (TDB) antibody including non BCMA targeting TDB
* 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
* 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) antimicrobials where the last dose of IV antimicrobial was given within 14 days prior to first study treatment
* Active symptomatic COVID-19 infection at study enrollment or requiring treatment with IV antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Participants 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 Epstein-Barr virus (EBV) polymerase chain reaction (PCR) or cytomegalovirus (CMV) PCR prior to first study treatment
* Known or suspected chronic active EBV 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 macrophage activation syndrome (MAS)
* 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/02/2027
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle; Hematology - Waratah
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
France
State/province [12] 0 0
Nantes
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Poitiers
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Köln
Country [18] 0 0
Germany
State/province [18] 0 0
Tübingen
Country [19] 0 0
Germany
State/province [19] 0 0
Würzburg
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Israel
State/province [22] 0 0
Tel-Aviv
Country [23] 0 0
Italy
State/province [23] 0 0
Emilia-Romagna
Country [24] 0 0
Italy
State/province [24] 0 0
Lombardia
Country [25] 0 0
Italy
State/province [25] 0 0
Piemonte
Country [26] 0 0
Spain
State/province [26] 0 0
Navarra
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO43476 https://forpatients.roche.com
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05535244