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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04910568




Registration number
NCT04910568
Ethics application status
Date submitted
27/05/2021
Date registered
2/06/2021

Titles & IDs
Public title
A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
Scientific title
An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab as Monotherapy and Cevostamab Plus Pomalidomide and Dexamethasone or Cevostamab Plus Daratumumab and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2021-000238-33
Secondary ID [2] 0 0
GO42552
Universal Trial Number (UTN)
Trial acronym
CAMMA 1
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
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Daratumumab
Treatment: Drugs - Dexamethasone

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.

Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. 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 14-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. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts.

Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts 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. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts.

Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S.


Treatment: Drugs: 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 Arm A, participants have the option to enter re-treatment after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.

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

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

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

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase II Dose (RP2D)
Timepoint [1] 0 0
Baseline up to approximately 4 years
Primary outcome [2] 0 0
Percentage of Participants with Adverse Events
Timepoint [2] 0 0
Baseline up to approximately 4 years
Primary outcome [3] 0 0
Percentage of Dose Interruptions
Timepoint [3] 0 0
Baseline up to approximately 4 years
Primary outcome [4] 0 0
Percentage of Dose Reductions
Timepoint [4] 0 0
Baseline up to approximately 4 years
Primary outcome [5] 0 0
Percentage of Dose Intensity
Timepoint [5] 0 0
Baseline up to approximately 4 years
Primary outcome [6] 0 0
Percentage of Treatment Discontinuation
Timepoint [6] 0 0
Baseline up to approximately 4 years
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Baseline up to approximately 4 years
Secondary outcome [2] 0 0
Complete Response/Stringent Complete Response (CR/sCR) Rate
Timepoint [2] 0 0
Baseline up to approximately 4 years
Secondary outcome [3] 0 0
Rate of Very Good Partial Response (VGPR) or Better
Timepoint [3] 0 0
Baseline up to approximately 4 years
Secondary outcome [4] 0 0
Progression-free Survival (PFS)
Timepoint [4] 0 0
Start of study treatment to first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
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 4 years)
Secondary outcome [6] 0 0
Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better)
Timepoint [6] 0 0
Baseline up to approximately 4 years
Secondary outcome [7] 0 0
Time to Best Response (for Participants who Achieve a Response of PR or Better)
Timepoint [7] 0 0
Baseline up to approximately 4 years
Secondary outcome [8] 0 0
Minimal Residual Disease (MRD) Negativity
Timepoint [8] 0 0
Baseline up to approximately 4 years
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
Baseline up until death from any cause (up to approximately 4 years)
Secondary outcome [10] 0 0
Serum Concentration of Cevostamab at Specified Timepoints
Timepoint [10] 0 0
Cevostamab Pre-Phase (CPP) Day (D) 1 up to approximately 3 years
Secondary outcome [11] 0 0
Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab
Timepoint [11] 0 0
CPP D1 up to approximately 4 years
Secondary outcome [12] 0 0
Maximum Observed Serum Concentration (Cmax) of Cevostamab
Timepoint [12] 0 0
CPP D1 up to approximately 4 years
Secondary outcome [13] 0 0
Minimum Observed Serum Concentration (Cmin) of Cevostamab
Timepoint [13] 0 0
CPP D1 up to approximately 4 years
Secondary outcome [14] 0 0
Clearance of Cevostamab
Timepoint [14] 0 0
CPP D1 up to approximately 4 years
Secondary outcome [15] 0 0
Volume of Distribution at Steady State of Cevostamab
Timepoint [15] 0 0
CPP D1 up to approximately 4 years
Secondary outcome [16] 0 0
Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
Timepoint [16] 0 0
Baseline
Secondary outcome [17] 0 0
Percentage of Participants with ADAs Against Cevostamab During the Study
Timepoint [17] 0 0
Up to approximately 4 years
Secondary outcome [18] 0 0
Serum Concentration of Pomalidomide
Timepoint [18] 0 0
From Cycle 1 Day 1 through Cycle 6 Day 15. Each cycle=28 days
Secondary outcome [19] 0 0
Serum Concentration of Daratumumab
Timepoint [19] 0 0
From C1D1 until disease progression or unexpected toxicity. Cycles 1-8 are 21 days and Cycle 9 onward are 28 days.

Eligibility
Key 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 B2S 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 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* 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

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/07/2025
Actual
Sample size
Target
184
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre; Department of Haematology - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital; Malignant Haematology & Stem Cell Transplant Service - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Czechia
State/province [8] 0 0
Ostrava
Country [9] 0 0
Czechia
State/province [9] 0 0
Prague 2
Country [10] 0 0
Denmark
State/province [10] 0 0
København Ø
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
France
State/province [12] 0 0
Poitiers
Country [13] 0 0
France
State/province [13] 0 0
Rennes
Country [14] 0 0
Israel
State/province [14] 0 0
Haifa
Country [15] 0 0
Israel
State/province [15] 0 0
Tel-Aviv
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Japan
State/province [17] 0 0
Okayama
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Japan
State/province [19] 0 0
Yamagata
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Poland
State/province [21] 0 0
Gda?sk
Country [22] 0 0
Poland
State/province [22] 0 0
Katowice
Country [23] 0 0
Poland
State/province [23] 0 0
Pozna?
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0

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
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GO42552 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
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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).


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/NCT04910568