CO43923 Master Protocol: A Study Evaluating the Safety and Efficacy of Multiple Treatments in Patients with Multiple Myeloma CO43923 Substudy 1: A Study to Collect Patient-Level Data in Patients with Multiple Myeloma CO43923 Substudy 2 Cevos + Len Treatment: A Study Evaluating the Safety and Efficacy of Cevostamab in Combination with Lenalidomide in Patients with Cytogenetic High-Risk Features Receiving Maintenance Treatment After First Response from Multiple Myeloma Post-Stem Cell Transplant CO43923 Substudy 4 Cevostamab+ Iberdomide Treatment: A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cevostamab in Combination with Iberdomide in Patients with Relapsed or 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

18 Nov 2022 → ongoing

Decision date (initial)

2024-07-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-504484-16-00

EudraCT number

2021-005918-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Others, Safety

CO43923 Master Protocol: - Stage 1: To evaluate the safety of the study treatment, including evaluation of the tolerability of the dosing schedules and doses - Stage 1: To characterize maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) when a dose-finding phase is used - Stage 2: To evaluate the efficacy of the study treatment based on objective response rate (ORR), rate of complete response (CR) or stringent complete response (sCR), rate of very good partial response (VGPR), progression-free survival (PFS) and overall survival (OS) CO43923 Substudy 1: To describe patient and disease characteristics and treatment patterns from initial diagnosis of patients with first-line and later lines of therapy in relapsed or refractory multiple myeloma (R/R MM) CO43923 Substudy 2 Cevos + Len Treatment: To evaluate the safety of cevostamab in combination with lenalidomide (Cevos + Len) as a maintenance treatment in patients with MM after autologous stem cell transplant (SCT) following first-line treatment
CO43923 Substudy 4 Cevostamab+ Iberdomide Treatment: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cevostamab in combination with iberdomide (Cevostamab + Iberdomide) in patients with R/R MM.

Secondary objectives 7

1. CO43923 Stage 1 (for maintenance substudies): To evaluate the preliminary efficacy of the study treatment
2. CO43923 Stage 1 (for all other substudies): To evaluate the preliminary efficacy of the study treatment
3. CO43923 Stage 2: To evaluate the efficacy of the study treatment based on duration of response (DOR), time to first response, time to best response, minimal residual disease (MRD) negativity rate
4. CO43923 Stage 2: To evaluate the safety of the study treatment
5. CO43923 Substudy 1: To describe treatment effectiveness and clinical outcomes in patients with first-line and later lines of therapy in R/R MM
6. CO43923 Substudy 1: To collect biological samples obtained as part of standard of care for use in preclinical, exploratory biomarker research, and translational studies
7. CO43923 Substudy 1: To collect safety (adverse event) information from patients with R/R MM who are treated with first-line and later lines of therapy in routine clinical practice

Conditions and MedDRA coding

Multiple Myeloma (MM)

Study design 3 periods

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. CO43923 Master Protocol: Diagnosed with multiple myeloma (MM) per International Myeloma Working Group (IMWG) criteria
2. CO43923 Master Protocol: Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
3. CO43923 Substudy 1: A current or past diagnosis of MM in the first line or later setting, including maintenance therapy
4. CO43923 Substudy 2 Cevos + Len Treatment: Completion of planned induction therapy and achievement of at least a partial response (PR)
5. CO43923 Substudy 4 Cevostamab+ Iberdomide Treatment: Previously exposed to at least a PI, an IMiD, and an anti-CD38 antibody for the treatment of R/R MM for whom no suitable SOC therapy options are available

Exclusion criteria 5

1. CO43923 Master Protocol: History of other malignancy within 2 years prior to screening, except those with negligible risk of metastasis or death
2. CO43923 Master Protocol: History of confirmed progressive multifocal leukoencephalopathy
3. CO43923 Master Protocol: Known history of HIV seropositivity
4. CO43923 Substudy 2 Cevos + Len Treatment: Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs
5. CO43923 Substudy 4 Cevostamab+ Iberdomide Treatment: Treatment with systemic immunosuppressive medications including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to starting pre-phase

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. 1. Stage 1: Incidence and severity of adverse events, including dose-limiting toxicities (DLTs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0); for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome(ICANS), severity is determined according to respective American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading Scales
2. 2. Stage 2: ORR, defined as the proportion of patients with a stringent complete response (sCR), CR, very good partial response (VGPR), or partial response (PR)
3. 3. Stage 2: Rate of CR or sCR, defined as proportion of patients achieving a CR or sCR
4. 4. Stage 2: Rate of VGPR or better, defined as the proportion of patients achieving a VGPR or better
5. 5. Stage 2: PFS, defined as the time from initiation of study treatment to the first occurrence of progressive disease or death from any cause (whichever occurs first)
6. 6. Stage 2: OS, defined as the time from initiation of study treatment to death from any cause

Secondary endpoints 18

1. 1. Stage 1 (maintenance substudies): Conversion to a better response (e.g., from PR to VGPR or better; or from VGPR to CR/sCR or from CR to sCR)
2. 2. Stage 1 (maintenance substudies): PFS, defined as the time from initiation of study treatment to the first occurrence of progressive disease or death from any cause (whichever occurs first)
3. 3. Stage 1 (maintenance substudies): OS, defined as the time from initiation of study treatment to death from any cause
4. 4. Stage 1 (maintenance substudies): MRD negativity rate, defined as proportion of patients who are MRD negative at any time by next-generation sequencing (NGS) on bone marrow aspirate
5. 5. Stage 1 (all other substudies): ORR, defined as the proportion of patients with a sCR, CR, VGPR, or PR
6. 6. Stage 1 (all other substudies): Rate of CR or sCR, defined as proportion of patients achieving a CR or sCR
7. 7. Stage 1 (all other substudies): Rate of VGPR or better, defined as the proportion of patients achieving a VGPR or better
8. 8. Stage 1 (all other substudies): PFS, defined as the time from initiation of study treatment to the first occurrence of progressive disease or death from any cause (whichever occurs first)
9. 9. CO43271 Stage 1 (all other substudies): DOR, defined as the time from the first documented objective response until disease progression or death from any cause, (whichever occurs first)
10. 10. Stage 1 (all other substudies): OS, defined as the time from initiation of study treatment to death from any cause
11. 11. Stage 1 (all other substudies): MRD negativity rate, defined as proportion of patients who are MRD negative at any time by NGS on bone marrow aspirate
12. 12. Stage 1 (all other substudies): Time to first response (for patients who achieve a response of PR or better), defined as time from initiation of study treatment to first achieving a PR or better
13. 13. Stage 1 (all other substudies): Time to best response (for patients who achieve a response of PR or better), defined as time from initiation of study treatment to achieving the deepest response
14. 14. Stage 2: DOR, defined as the time from the first documented objective response until disease progression or death from any cause (whichever occurs first)
15. 15. Stage 2: Time to first response (for patients who achieve a response of PR or better), defined as time from initiation of study treatment to achieving a PR or better
16. 16. Stage 2: Time to best response (for patients who achieve a response of PR or better), defined as time from initiation of study treatment to achieving the deepest response
17. 17. Stage 2: MRD negativity rate, defined as proportion of patients who are MRD negative by NGS on bone marrow aspirate
18. 18. Stage 2: Incidence and severity of adverse events, including DLTs, with severity determined according to NCI CTCAE v5.0; for CRS and ICANS, severity is determined according to ASTCT Consensus Grading Scales

Investigational products

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

Test 8

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

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 8

Locations

4 EU/EEA countries · 13 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 72 files

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

Application history

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