| 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). |
|
| 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). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
1. Compare the Overall Survival (OS).
2. Evaluate Overall Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), as assessed by CAC blinded central review using IMWG criteria [1], and second Progression Free Survival (PFS2) by investigator assessment, between treatment arms.
3. Evaluate the safety and tolerability in both treatment arms.
|
|
| 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 |
Bone marrow exploratory sub-study: a subset of subjects (up to 50
subjects per arm from selected sites only) could choose to participate in a Bone marrow sub-study and may choose
to provide a newly obtained bone marrow aspirate sample at baseline (screening or C1D1), C2D1 and at the time of
discontinuation to undergo testing for the purposes of biomarker characterisation. |
|
| 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:
-> or = 10% bone marrow plasma cell percentage or biopsy proven bony or extramedullary plasmacytoma and
-Serum monoclonal protein (M-protein) levels > or = 0.5 g/dL or
-Urine monoclonal protein (M-protein) levels > or =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 > or = 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 (> or = 65 years old) or any significant coexisting medical condition (cardiac, renal, pulmonary or hepatic dysfunction), likely to have a negative impact on tolerability of auto-SCT. Subjects < 65 years old who refuse ASCT are not eligible for this study. Note: Sponsor review and approval of participants <65 years old is required before randomization.
4.Provide at screening, archival (< or = 60 days prior to screening date) or newly obtained bone marrow biopsy or aspirate material for disease assessment at the local institutions and MRD characterization for central analysis. Subjects that have agreed to participate in the bone marrow aspirate exploratory sub-study (selected US sites ONLY) should be able to provide a newly obtained bone marrow aspirate for central analysis.
5.Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
|
|
| E.4 | Principal exclusion criteria |
1.Has oligo-secretory myeloma, smoldering MM, monoclonal gammopathy of undetermined significance, Waldenström's macroglobulinemia, or any history of plasma cell leukemia.
2.History of repeated infections, primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
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, lenalidomide, or pembrolizumab.
6.Subjects with peripheral neuropathy > or = Grade 2.
7.Has a history of (non-infectious) pneumonitis that required steroids or current 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.
9.Is unable or unwilling to undergo thromboembolic prophylaxis including, as clinically indicated, aspirin, Coumadin (warfarin) or low-molecular weight heparin.
10.Has lactose intolerance.
11.Has an invasive fungal infection.
|
|
| 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 2011) 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.
|
|
| 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.
|
|
| 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, by investigator assessment.
|
|
| 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). |
|
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 |
| Ireland |
| Israel |
| Italy |
| Japan |
| Norway |
| Russian Federation |
| South Africa |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
| LVLS or the Sponsor ends the trial, whichever occurs first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 12 |
| 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 |
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