PLYCOM: A Study Evaluating the Safety and Efficacy of Multiple Treatment Combinations in Participants With Multiple Myeloma
Study Details
Study Description
Brief Summary
CO43923 is a platform study that will evaluate the safety, efficacy, and pharmacokinetics (PK) of multiple treatment combinations in subsets of patients with multiple myeloma (MM). The study is designed with the flexibility to open new treatment substudies as new treatments become available. Information regarding the substudy opened is found below.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Cevos + Len substudy 2: This substudy will explore the combination of cevostamab and lenalidomide as post-transplant maintenance therapy in participants with MM with high-risk cytogenetic features who experienced at least a partial response (PR) after induction.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Substudy 2: Escalation Phase In Cycle 1, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on Cycle(C) 1 Day(D)1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on D1 and D15 for cycles 2-6 and D1 of cycle 7 onwards. Each cycle is 28 days. Lenalidomide will be administered by mouth (PO) on a 28-day cycle. |
Drug: Cevostamab
Cevostamab will be administered intravenously on a 28-day cycle, up to a total of 13 cycles.
Drug: Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
|
| Experimental: Substudy 2: Expansion Phase During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Lenalidomide will be administered PO on a 28-day cycle. |
Drug: Cevostamab
Cevostamab will be administered intravenously on a 28-day cycle, up to a total of 13 cycles.
Drug: Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
|
Outcome Measures
Primary Outcome Measures
- Stage 1: Percentage of Participants with Adverse Events (AEs) [Baseline up to approximately 5 years]
- Stage 2: Objective Response Rate (ORR) [Baseline up to approximately 5 years]
- Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) Rate [Baseline up to approximately 5 years]
- Stage 2: Rate of Very Good Partial Response (VGPR) or Better [Baseline up to approximately 5 years]
- Stage 2: Progression-free Survival (PFS) [Baseline up to approximately 5 years]
- Stage 2: Overall Survival (OS) [Baseline up to approximately 5 years]
Secondary Outcome Measures
- Stage 1: Conversion to a Better Response [Baseline up to approximately 5 years]
- Stage 1: PFS [Baseline up to approximately 5 years]
- Stages 1 and 2: Duration of Response (DOR) [Baseline up to approximately 5 years]
- Stage 1: OS [Baseline up to approximately 5 years]
- Stages 1 and 2: Minimal Residual Disease (MRD) Negativity Rate [Baseline up to approximately 5 years]
- Stage 1: ORR [Baseline up to approximately 5 years]
- Stage 1: CR or sCR Rate [Baseline up to approximately 5 years]
- Stage 1: Rate of VGPR or Better [Baseline up to approximately 5 years]
- Stage 2: Stage 1: Percentage of Participants with AEs [Baseline up to approximately 5 years]
- Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better) [Baseline up to approximately 5 years]
- Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better) [Baseline up to approximately 5 years]
- Stages 1 and 2: Maximum Concentration Observed (Cmax) [Baseline up to approximately 5 years]
- Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin) [Baseline up to approximately 5 years]
- Stages 1 and 2: Time to Maximum Concentration (Tmax) [Baseline up to approximately 5 years]
- Stages 1 and 2: Area under the Concentration-Time Curve (AUC) [Baseline up to approximately 5 years]
- Stages 1 and 2: Total Clearance of Drug (CL) [Baseline up to approximately 5 years]
- Stages 1 and 2: Volume of Distribution at Steady State [Baseline up to approximately 5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosed with MM per International Myeloma Working Group (IMWG) criteria
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Eastern Cooperative Oncology Group Performance Status of 0, or 1, or 2
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Resolution of AEs from prior anti-cancer therapy to Grade <=1
-
Agreement to undergo scheduled assessments and procedures
Additional Inclusion Criteria for Substudy 2:
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Completion of planned induction therapy and achievement of at least a partial response (PR)
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Autologous Stem Cell Transplant (ASCT) within 100 days prior to first study treatment and the absence of progressive disease
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Cytogenetic high-risk features at diagnosis
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Treatment with any investigational medicinal products, systemic cancer therapies, immunotherapies received previously in CO43923 (any arms) within 5 half-lives or 3 weeks whichever is the shortest
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Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program
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For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
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For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom even if they have had a prior vasectomy, and agreement to refrain from donating sperm
Exclusion Criteria:
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Inability to comply with protocol-mandated hospitalization and procedures
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History of confirmed progressive multifocal leukoencephalopathy
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History of other malignancy within 2 years prior to screening
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Current or past history of central nervous system (CNS) disease
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Significant cardiovascular disease that may limit a participant's ability to adequately respond to a CRS event
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Symptomatic active pulmonary disease or requiring supplemental oxygen
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Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics where the last dose of IV antibiotics was given within 14 days prior to first study treatment
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Known or suspected chronic active Epstein-Barr virus (EBV) infection
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Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
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Acute or chronic hepatitis C virus (HCV) infection
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Known history of HIV seropositivity
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Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study
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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
Additional Exclusion Criteria for Substudy 2:
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Severe hypersensitivity reactions to lenalidomide
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History of autoimmune disease
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Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
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History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
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Harbor lesions at proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
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Chronic treatment with more than 10 milligrams (mg)/day of corticosteroids. The maximal authorized dose of corticosteroids in the study is 10 mg/day when not used to treat an AE or as a premedication for cevostamab dosing
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History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
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Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | 003-722 | |
| 2 | Samsung Medical Center | Seoul | Korea, Republic of | 135-710 | |
| 3 | Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii | Gdansk | Poland | 80-952 | |
| 4 | Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie | Olsztyn | Poland | 10-228 | |
| 5 | Fundacion Jimenez Diaz; Servicio de Hematologia | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CO43923
- 2021-005918-34