Multiple MyelomaPhase 1CAMMA 1NCT04910568
A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Cevostamab, Tocilizumab and Pomalidomide in people with Multiple Myeloma, run by Genentech, Inc. at 34 sites in 13 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Cevostamab, Tocilizumab and Pomalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 34 sitesin 13 countries
- Study dates
- 26 Jul 2021to 21 Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
34 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: GO42552 https://forpatients.roche.com/No attachments to email below. contact
34 sites in 13 countries
United States6 sites, 1 recruiting
- Withdrawn
Winship Cancer Institute
Atlanta, Georgia, 30322
- Recruiting
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, 80218
- Completed
Karmanos Cancer Institute.
Detroit, Michigan, 48201
- Active, not recruiting
City of Hope
Duarte, California, 91010
- Active, not recruiting
City of Hope - Lennar Foundation Cancer Center
Irvine, California, 92618
- Active, not recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Japan4 sites
- Withdrawn
Nagoya City University Hospital
Aichi, 467-8602
- Withdrawn
National Hospital Organization Okayama Medical Center
Okayama, 701-1192
- Withdrawn
The Cancer Institute Hospital of JFCR
Tokyo, 135-8550
- Active, not recruiting
Yamagata University Hospital
Yamagata, 990-9585
Canada3 sites
- Active, not recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
- Active, not recruiting
Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
- Active, not recruiting
University Health Network
Toronto, Ontario, M5G 2M9
France3 sites
- Withdrawn
Hôpital Saint-Louis
Paris, 75475
- Active, not recruiting
CHU de Poitiers - La Miletrie
Poitiers, 86021
- Withdrawn
CHU Pontchaillou
Rennes, 35003
Poland3 sites
- Withdrawn
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214
- Active, not recruiting
Pratia Onkologia Katowice
Katowice, 41-500
- Withdrawn
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, 60-569
Australia2 sites, 1 recruiting
- Active, not recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3002
- Recruiting
The Alfred Hospital
Melbourne, Victoria, 3004
Czechia2 sites
- Active, not recruiting
Fakultni Nemocnice Ostrava
Ostrava, 708 52
- Withdrawn
I Interni klinika
Prague, 128 08
Israel2 sites, 1 recruiting
- Active, not recruiting
Rambam Medical Center
Haifa, 3109601
- Recruiting
Sourasky Medical Centre
Tel Aviv, 6423906
Italy2 sites
- Active, not recruiting
Asst Papa Giovanni Xxiii
Bergamo, Lombardy, 24127
- Completed
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
Brescia, Lombardy, 25123
South Korea2 sites
- Active, not recruiting
Seoul National University Hospital
Seoul, 03080
- Active, not recruiting
Samsung Medical Center
Seoul, 06351
Spain2 sites
- Active, not recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Active, not recruiting
Hospital General Universitario Gregorio Marañon
Madrid, 28009
United Kingdom2 sites, 1 recruiting
- Recruiting
University College London Hospitals NHS Foundation Trust
London, W1T 7HA
- Active, not recruiting
Royal Marsden Hospital
Sutton, SW3 6JJ
About this study
Official 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
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.
- Conditions
- Multiple Myeloma
- Being tested
- Cevostamab, Tocilizumab, Pomalidomide, Daratumumab, Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CevostamabDrug
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 within 12 months of the end of treatment visit. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
TocilizumabDrug
Also called Actemra/RoActemra
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
PomalidomideDrug
Pomalidomide will be administered orally (PO) on a 28-day cycle.
DaratumumabDrug
Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).
DexamethasoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single-Agent Cevostamab (Arm A) | Experimental | 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. Receives: Drug: Cevostamab; Drug: Tocilizumab; Drug: Dexamethasone |
| Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B) | Experimental | 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 (Cohorts B1E and B3E). An additional non-randomized expansion cohort (Cohort B4E) will be included. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S. Receives: Drug: Cevostamab; Drug: Tocilizumab; Drug: Pomalidomide; Drug: Dexamethasone |
| Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C) | Experimental | 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. Receives: Drug: Cevostamab; Drug: Tocilizumab; Drug: Daratumumab; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase II Dose (RP2D)
Measured: Baseline up to approximately 4 years
Percentage of Participants with Adverse Events
Measured: Baseline up to approximately 4 years
Percentage of Dose Interruptions
Measured: Baseline up to approximately 4 years
Percentage of Dose Reductions
Measured: Baseline up to approximately 4 years
Percentage of Dose Intensity
Measured: Baseline up to approximately 4 years
Percentage of Treatment Discontinuation
Measured: Baseline up to approximately 4 years
Secondary outcomes (18)
Objective Response Rate (ORR)
Measured: Baseline up to approximately 4 years
Complete Response/Stringent Complete Response (CR/sCR) Rate
Measured: Baseline up to approximately 4 years
Rate of Very Good Partial Response (VGPR) or Better
Measured: Baseline up to approximately 4 years
Progression-free Survival (PFS)
Measured: Start of study treatment to first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Duration of Response (DOR)
Measured: 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)
Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better)
Measured: Baseline up to approximately 4 years
Time to Best Response (for Participants who Achieve a Response of PR or Better)
Measured: Baseline up to approximately 4 years
Overall Survival (OS)
Measured: Baseline up until death from any cause (up to approximately 4 years)
Serum Concentration of Cevostamab at Specified Timepoints
Measured: Cevostamab Pre-Phase (CPP) Day (D) 1 up to approximately 3 years
Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab
Measured: CPP D1 up to approximately 4 years
Maximum Observed Serum Concentration (Cmax) of Cevostamab
Measured: CPP D1 up to approximately 4 years
Minimum Observed Serum Concentration (Cmin) of Cevostamab
Measured: CPP D1 up to approximately 4 years
Clearance of Cevostamab
Measured: CPP D1 up to approximately 4 years
Volume of Distribution at Steady State of Cevostamab
Measured: CPP D1 up to approximately 4 years
Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
Measured: Baseline
Percentage of Participants with ADAs Against Cevostamab During the Study
Measured: Up to approximately 4 years
Serum Concentration of Pomalidomide
Measured: From Cycle 1 Day 1 through Cycle 6 Day 15. Each cycle=28 days
Serum Concentration of Daratumumab
Measured: From C1D1 until disease progression or unexpected toxicity. Cycles 1-8 are 21 days and Cycle 9 onward are 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2021
- Study start26 Jul 2021
- Primary completion21 Dec 2028 (estimated)
- Study completion21 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04910568
- Sponsor's protocol ID
- GO42552
- Other IDs
- 2021-000238-33, 2023-507019-36-00, 2023
- Acronym
- CAMMA 1
- Status last verified
- Oct 2026
- First submitted
- 27 May 2021
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No