CO43923 Master Protocol: A Platform Study Evaluating the Safety and Efficacy of Multiple Treatments in Patients with Multiple Myeloma CO43923 Substudy 1: A Non-Interventional Study to Collect Patient-Level Data in Patients with Multiple Myeloma CO43923 Substudy 2 Cevos + Len Treatment: A Phase Ib, Single Arm, Open-Label 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 Phase Ib, Single Arm, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cevostamab in Combination with Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma
Overview
- Phase
- Phase 1/2
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- F. Hoffmann-La Roche AG
- Enrollment
- 32
- Locations
- 13
- Primary Endpoint
- 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
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG
Eligibility Criteria
Inclusion Criteria
- •CO43923 Master Protocol: Diagnosed with multiple myeloma (MM) per International Myeloma Working Group (IMWG) criteria
- •CO43923 Master Protocol: Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- •CO43923 Substudy 1: A current or past diagnosis of MM in the first line or later setting, including maintenance therapy
- •CO43923 Substudy 2 Cevos + Len Treatment: Completion of planned induction therapy and achievement of at least a partial response (PR)
- •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
- •CO43923 Master Protocol: History of other malignancy within 2 years prior to screening, except those with negligible risk of metastasis or death
- •CO43923 Master Protocol: History of confirmed progressive multifocal leukoencephalopathy
- •CO43923 Master Protocol: Known history of HIV seropositivity
- •CO43923 Substudy 2 Cevos + Len Treatment: Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs
- •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
Outcomes
Primary Outcomes
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
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. 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)
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. Stage 2: Rate of CR or sCR, defined as proportion of patients achieving a CR or sCR
3. Stage 2: Rate of CR or sCR, defined as proportion of patients achieving a CR or sCR
4. Stage 2: Rate of VGPR or better, defined as the proportion of patients achieving a VGPR or better
4. Stage 2: Rate of VGPR or better, defined as the proportion of patients achieving a VGPR or better
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)
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. Stage 2: OS, defined as the time from initiation of study treatment to death from any cause
6. Stage 2: OS, defined as the time from initiation of study treatment to death from any cause
Secondary Outcomes
- 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. 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. Stage 1 (maintenance substudies): OS, defined as the time from initiation of study treatment to death from any cause
- 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. Stage 1 (all other substudies): ORR, defined as the proportion of patients with a sCR, CR, VGPR, or PR
- 6. Stage 1 (all other substudies): Rate of CR or sCR, defined as proportion of patients achieving a CR or sCR
- 7. Stage 1 (all other substudies): Rate of VGPR or better, defined as the proportion of patients achieving a VGPR or better
- 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. 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. Stage 1 (all other substudies): OS, defined as the time from initiation of study treatment to death from any cause
- 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. 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. 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. 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. 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. 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. Stage 2: MRD negativity rate, defined as proportion of patients who are MRD negative by NGS on bone marrow aspirate
- 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