E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed, treatment-naïve multiple myeloma (MM) who are ineligible for autologous stem cell transplant (auto-SCT). |
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E.1.1.1 | Medical condition in easily understood language |
Newly diagnosed, never treated multiple myeloma (MM) who are not eligible for his/her own stem cell transplant (auto-SCT). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Compare the Progression Free Survival (PFS) as assessed by independent central review according to the International Myeloma Working Group response criteria, (IMWG criteria) between treatment arms. |
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E.2.2 | Secondary objectives of the trial |
1.Compare the Overall Survival (OS).
2.Evaluate Overall Response Rate (ORR), Disease Control Rate (DCR), and Duration of Response (DOR) as assessed by independent central review and as per investigator assessment using IMWG criteria or European Group for Blood and Marrow Transplantation (EBMT) criteria for minor response only.
3.Compare the Progression Free Survival (PFS) and second Progression Free Survival (PFS2) as assessed by the investigator using IMWG criteria between treatment arms.
4.To evaluate the safety and tolerability in both treatment arms.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal inclusion criteria |
1.Newly diagnosed, treatment-naïve, ASCT ineligible, symptomatic MM (CRAB features).
2.Confirmed diagnosis of active MM and measurable disease defined as:
-Serum monoclonal protein (M-protein) levels ≥ 0.5 g/dL or
-Urine monoclonal protein (M-protein) levels ≥200 mg/24-hours or
-Subjects without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L. (Normal serum FLC κ/λ value: 0.26 - 1.65)
-Presence of CRAB features
3.Must be ineligible to receive treatment with ASCT due to age (≥65 years old) or coexisting medical condition. Subjects < 65 years old who refuse ASCT are not eligible for this study.
4.Provide, archival (≤60 days) or newly obtained bone marrow biopsy or aspirate material for disease assessment and biomarker analysis.
5.Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
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E.4 | Principal exclusion criteria |
1.Subjects with non-secretory or oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia.
2.History of repeated infections, primary amyloidosis, hyperviscosity or POEMS syndrome.
3.Has had prior anti-myeloma therapy including but not limited to dexamethasone, IMiDs, proteasome inhibitors, chemotherapy, monoclonal antibody, ASCT or radiation therapy.
4.Has undergone prior allogeneic hematopoetic stem cell transplantation (HSCT) within the last 5 years.
5.Has known hypersensitivity to dexamethasone.
6.Subjects with peripheral neuropathy ≥ Grade 2.
7.Has evidence of active, non-infectious pneumonitis.
8.Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point of the study is Progression-free survival (PFS) – the International Myeloma Working Group response criteria (IMWG 2006) by blinded central review.
PFS is defined as the time from randomization to the first documented disease progression per IMWG 2006 based on blinded central review or death due to any cause, whichever occurs first.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Interim PFS Analysis: ~ 20 months after trial starts (when all subjects enrolled and ~ 115 PFS events are observed).
2.Final PFS Analysis: ~ 20 months after interim PFS analysis and ~227 PFS events are observed.
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E.5.2 | Secondary end point(s) |
1.Overall Survival (OS): OS is defined as the time from randomization to death due to any cause.
2.Overall Response Rate (ORR): ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR).
3.Duration of Response (DOR): For subjects who demonstrated CR or PR, response duration is defined as the time from first documented evidence of CR or PR until disease progression or death.
4.Second Progression Free Survival (PFS2): PFS2 is the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever comes first.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
~ 41 months after trial starts (when last subject completes its last phone call follow-up). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
France |
Germany |
Israel |
Italy |
Japan |
Norway |
Russian Federation |
South Africa |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |