A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— CAMMA 2  

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05535244
• Other study ID #: CO43476
• Secondary ID: 2021-006816-10
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 18, 2022
• Est. completion date: February 26, 2027

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO43476 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of cevostamab in participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 26, 2027
• Est. primary completion date: February 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Cevostamab
Cevostamab will be administered by IV infusion in 21-day cycles.
• Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Calvary Mater Newcastle; Hematology	Waratah	New South Wales
Belgium	UZ Leuven Gasthuisberg	Leuven
France	APHP - Hospital Saint Louis	Paris
France	CHU de Poitiers - La Miletrie; Oncologie hematologique - Pole Regional de Cancerologie	Poitiers
Germany	CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie	Berlin
Germany	Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II	Hamburg
Germany	Klinik der Uni zu Köln; Klinik für Innere Medizin	Köln
Germany	Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II	Tübingen
Germany	Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie	Würzburg
Israel	Hadassah Ein Karem Hospital; Haematology	Jerusalem
Israel	Sheba Medical Center; Tel Hashomer	Ramat Gan
Israel	Sourasky Medical Centre	Tel-Aviv
Italy	ASST PAPA GIOVANNI XXIII; Ematologia	Bergamo	Lombardia
Italy	Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli"	Bologna	Emilia-Romagna
Italy	Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia	Milano	Lombardia
Italy	A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette; Ematologia I	Torino	Piemonte
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Hematología	Madrid
Spain	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Hematologia	Pamplona	Navarra
Spain	Hospital Universitario la Fe; Servicio de Hematologia	Valencia
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai (ISMMS); The Derald H. Ruttenberg Treatment Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic - Arizona	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Hunstman Cancer Institute	Salt Lake City	Utah
United States	Methodist Hospital	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimal Residual Disease (MRD) Negative Rate		Baseline up to approximately 2 years
Primary	Objective Response Rate (ORR) as Determined by the Investigator		Baseline up to approximately 2 years
Primary	Percentage of Participants with Adverse Events		Baseline up to approximately 2 years
Secondary	ORR as Determined by the Independent Review Committee (IRC)		Baseline up to approximately 2 years
Secondary	Duration of Response (DOR)		Baseline up to approximately 2 years
Secondary	Rate of Complete Response (CR) or Better		Baseline up to approximately 2 years
Secondary	Rate of Very Good Partial Response (VGPR) or Better		Baseline up to approximately 2 years
Secondary	Overall Survival (OS)		Baseline up until death from any cause (up to approximately 2 years)
Secondary	Progression-free Survival (PFS)		Baseline up to approximately 2 years
Secondary	Time to First Response (for Participants who Achieve an Objective Response)		Baseline up to approximately 2 years
Secondary	Time to Best Response (for Participants who Achieve an Objective Response)		Baseline up to approximately 2 years
Secondary	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		Baseline up to approximately 2 years
Secondary	Time to Deterioration in the Fatigue Domain of the EORTC QLQ-C30 and/or Disease Symptoms Domain of the EORTC QLQ-MY20		Baseline up to approximately 2 years
Secondary	Serum Concentration of Cevostamab at Specified Timepoints		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	Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline		Baseline
Secondary	Percentage of Participants with ADAs Against Cevostamab During the Study		Up to approximately 2 years
Secondary	Cytokine Release Syndrome (CRS) Following Administration of Tocilizumab		Baseline up to approximately 2 years
Secondary	Relationship Between Serum Concentration of Cevostamab and Cytokine Release		Baseline up to approximately 2 years
Secondary	Relationship Between Serum Concentration of Cevostamab and T Cell Number		Baseline up to approximately 2 years
Secondary	Relationship Between Serum Concentration of Cevostamab and T-cell Activation State		Baseline up to approximately 2 years