A Study to Evaluate the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen-Exposed Patients with Relapsed/Refractory Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Oct 2022 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505865-94-00

EudraCT number

2021-006816-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Others, Safety

To evaluate the efficacy of cevostamab based on investigator assessed Objective response rate (ORR) To evaluate the safety and tolerability of cevostamab

Secondary objectives 5

1. To evaluate the efficacy of cevostamab based on IRC assessed ORR, DOR, CR or better, rate of VGPR or better, OS, PFS, time to first response, time to best response, proportion of participants experiencing a clinically meaningful improvement and time to deterioration assessed by EORTC QLQ-C30 and EORTC QLQ-MY20
2. To characterize the PK of cevostamab in participants with MM
3. To evaluate the immune response to cevostamab, potential relationships between cevostamab exposure and pharmacodynamic biomarkers
4. To make a preliminary assessment of the efficacy of tocilizumab in ameliorating the symptoms of CRS following treatment with cevostamab
5. To identify biomarkers that may be: - Able to provide evidence of cevostamab activity and to increase the knowledge and understanding of disease biology - Predictive of response to cevostamab - Associated with progression to a more severe disease state, acquired resistance to cevostamab and susceptibility to developing adverse events

Conditions and MedDRA coding

Relapsed/Refractory Multiple Myeloma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria
2. Evidence of progressive disease based on investigators determination of response by IMWG criteria on or after their last dosing regimen
3. Prior B cell maturation antigen (BCMA) antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T) Cohort: participants who have received a BCMA-targeted CAR-T or ADC therapy and are triple-class relapsed or refractory
4. Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting T-cell-dependent bispecific (TDB) antibody and are triple-class relapsed or refractory
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
6. Life expectancy is at least 12 weeks

Exclusion criteria 6

1. Inability to comply with protocol-mandated hospitalization
2. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of cevostamab or within 3 months after the last dose of tocilizumab
3. Prior treatment with cevostamab or another agent with the same target
4. Prior BCMA ADC or CAR-T Cohort: prior treatment with any T cell dependent bi‑specific antibody (TDB) antibody including non BCMA targeting TDB
5. Prior BCMA Bispecific Cohort: treatment with TDB antibody within 12 weeks prior to enrollment in the study
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. ORR, defined as the proportion of participants with an objective response [stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)], based on investigator-assessed response, according to IMWG criteria
2. 2. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) for CRS and of immune effector cell associated neurotoxicity syndrome (ICANS) grading

Secondary endpoints 16

1. 1. ORR, defined as the proportion of participants with an objective response based on independent review committee (IRC)-assessed response
2. 2. Duration of response (DOR), defined as the time from the first occurrence of an objective response until the date of disease progression or death from any cause (whichever occurs first), as determined separately by the IRC and the investigator
3. 3. Rate of CR or better, defined as the proportion of participants who achieve a response of sCR or CR, as assessed separately by IRC and the investigator
4. 4. Rate of VGPR or better, defined as the proportion of participants who achieve a response of VGPR or better, as assessed separately by IRC and the investigator
5. 5. Overall survival (OS), defined as the time from initiation of study treatment to death from any cause
6. 6. Progression-free survival (PFS), defined as the time from initiation of study treatment to the first occurrence of disease progression, relapse, or death from any cause (whichever occurs first), as assessed separately by IRC and the investigator
7. 7. Time to first response (for participants who achieve an objective response), defined as time from initiation of study treatment to first achieving an objective response (separate analyses by IRC and investigator)
8. 8. Time to best response (for participants who achieve an objective response), defined as time from initiation of study treatment to achieving the deepest response (separate analyses by IRC and investigator)
9. 9. Proportion 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 (QLQC-30) and EORTC QLQ-MY20
10. 10. Time to deterioration in the fatigue domain of the EORTC QLQ-C30 and/or disease symptoms domain of the EORTC QLQ-MY20
11. 11. Serum concentration of cevostamab at specified timepoints
12. 12. Pharmacokinetics (PK) parameters of cevostamab, as data allow
13. 13. Prevalence of anti-drug antibodies (ADAs) against cevostamab at baseline and incidence of ADAs against cevostamab during the study
14. 14. CRS outcome following administration of tocilizumab (e.g., time to CRS resolution, doses of tocilizumab administered, relationship between serum concentration or other PK parameters for tocilizumab and pharmacodynamic biomarkers)
15. 15. Relationship between serum concentration or other PK parameters for cevostamab and pharmacodynamic biomarkers, including, but not limited to, cytokine release, T cell number, and T-cell activation state
16. 16. Relationship between biomarkers in blood, bone marrow biopsies and aspirates, and tumor tissue and efficacy, safety, PK, immunogenicity, or other biomarker endpoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel Town

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 5

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications