Table 2.
Ongoing clinical trials of elotuzumab combinations in high-risk smoldering MM, newly diagnosed MM and RRMM
| Trial | Phase | Patient population | Primary end point | Study arm(s) |
|---|---|---|---|---|
| Phase II trial of combination of Elo, lenalidomide and dexamethasone in high-risk smoldering MM (NCT02279394) | Phase II | High-risk MM | PFS | Elotuzumab: 10 mg/kg IV; D1, 8, 15, 22, C1–2; 10 mg/kg IV; D1, 15, C3–8 Lenalidomide: 25 mg oral; D1–21, C1–24 Dexamethasone: 40 mg oral; D1, 8, 15, 22, C1–2; 40 mg oral; D1, 8, 15, C3–8 |
| A Phase II study of Elo with pomalidomide, bortezomib and dexamethasone in relapsed and refractory MM (NCT02718833) | Phase II | RRMM | ORR, treatment-related adverse events | 28-Day cycle: For C1–2, Elo IV is given weekly. For C3–8, Elo IV is given every other week. For C9+, Elo IV is given on D1, pomalidomide PO on D1–21, bortezomib SC on D1, 8, 15, dexamethasone PO and IV combination |
| A Phase 1 study of Elo in combination with ASCT and lenalidomide maintenance for MM (NCT02655458) | Phase Ib | MM patients who are receiving or have completed induction chemo and achieved at least a PR; eligible for ASCT for consolidation | Incidence of completion of treatment, safety and tolerability | Experimental: ASCT, Elo, lenalidomide Maximum number of cycles is 12. Elo IV 20 mg/kg on D1 of each cycle. Lenalidomide dosing starts with C4 at 10 mg PO on D1–21. Dexamethasone 8 mg IV on the day of Elo infusion |
| A randomized Phase I/II study of optimal induction therapy of bortezomib, dexamethasone and lenalidomide with or without Elo in treating patients with newly diagnosed high-risk MM (NCT01668719) | Phase I/II | Newly diagnosed high-riska MM | PFS | Arm 1: Induction: bortezomib SC or IV on D1, 4, 8, 11; lenalidomide PO QD on D1–14; dexamethasone PO or IV on D1, 2, 4, 5, 8, 9, 11, 12. Q21-day cycles ×8C. Maintenance: bortezomib SC or IV on D1, 8, 15; lenalidomide PO QD on D1–21; dexamethasone PO on D1, 8, 15. Q28-day cycles Arm 2: Induction: Arm 1+ elo IV on D1, 8, 15 of C1 and C2 and on D1, 11 of C3–8. Q21-day cycles ×8C Maintenance: Arm 1+ elo IV on D1, 15. Q28-day cycles |
| CheckMate 602 An open-label, randomized Phase III trial of combinations of nivolumab, Elo, pomalidomide and dexamethasone in RRMM (NCT02726581) |
Phase III (CheckMate 602) |
RRMM patients who have received ≥2 lines of prior therapy that must have included an IMiD and a proteasome inhibitor |
ORR PFS |
Arm A: (Investigational arm) nivolumab, pomalidomide, dexamethasone Arm B: (Control arm) pomalidomide and dexamethasone Arm C: (Exploratory arm) nivolumab, elotuzumab, pomalidomide and dexamethasone |
| An open-label, single arm, Phase IIa study of bortezomib, lenalidomide, dexamethasone and Elo in newly diagnosed MM (NCT02375555) | Phase II | Newly diagnosed MM | ORR | Experimental: elotuzumab, lenalidomide, bortezomib, dexamethasone (E-RVD). Induction cycles (1–8) are 21-day cycles. Stem cell mobilization performed for all subjects at the end of cycle 4. Subjects may elect to stop at C4 and proceed to ASCT. Those who do not wish to proceed will receive 8 cycles of induction therapy. Maintenance schedule (28 days) will start after 8 cycles of induction regimen for patients not proceeding with ASCT or after recovery from SCT for patients proceeding with it. Specific maintenance regimen determined by risk category |
| ELOQUENT-3 An open-label, randomized Phase II trial of pomalidomide/dexamethasone with or without Elo in RRMM (NCT02654132) |
Phase II | RRMM patients who have received ≥2 prior lines of therapy that must have included 2 consecutive cycles of lenalidomide and a proteasome inhibitor alone or in combination | PFS | Experimental arm: elotuzumab IV 10 mg/kg (C1 and C2 weekly on D1, 8, 15, 22), Elo IV 20 mg/kg (C3 and beyond on D1) + pomalidomide PO 4 mg QD on D1–21+ dexamethasone weekly on D1, 8, 15, 22 Control arm: pomalidomide PO 4 mg QD on D1–21+ dexamethasone weekly on D1, 8, 15, 22 |
| Phase II study of combination of Elo with lenalidomide as maintenance post ASCT in patients with MM (NCT02420860) | Phase II | MM patients who have undergone ASCT, within 18 months of initiation of induction therapy. Studied in the maintenance setting following ASCT | PFS | Experimental arm: Elo + lenalidomide Elo 10 mg/kg IV on D1, 8, 15, 21 for the first 2 cycles, then on D1, 15 only during cycles 3–6, then on D1 each cycle after that. Then for cycles beyond 6, once per cycle at 20 mg/kg on D1 of each cycle. Dexamethasone PO and IV. Lenalidomide 10 mg/day; after 3 cycles, dose may be increased to 15 mg/day at MD discretion and tolerability. Cycle length is 28 days |
| A randomized Phase III trial on the effect of Elo in VRD induction/consolidation and lenalidomide maintenance in newly diagnosed myeloma (NCT0249522) | Phase III (GMMG-HD6) |
Newly diagnosed MM | PFS | Active comparator (A1): Induction therapy with VRD 21 days per cycle, intensification (mobilization and ASCT), consolidation therapy with 2 cycles VRD, 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide (dexamethasone on D1, 15 in C1–6 and on D1 in C7–26) Experimental (A2): Induction therapy with 4 cycles VRD 21 days per cycle, intensification (mobilization and ASCT), consolidation therapy with 2 cycles VRD + elotuzumab 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide + elotuzumab (dexamethasone on D1, 15 in C1–6 and on D1 in C7–26) Experimental (B1): Induction therapy with 4 cycles VRD + elotuzumab, 21 days per cycle, intensification (mobilization and ASCT), consolidation therapy with 2 cycles VRD 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide (dexamethasone on D1, 15 in C1–6 and on D1 in C7–26) Experimental (B2): Induction therapy with 4 cycles VRD + elotuzumab, 21 days per cycle, intensification (mobilization and ASCT), consolidation therapy with 2 cycles VRD + elotuzumab, 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide + elotuzumab (dexamethasone on D1, 15 in C1–6 and on D1 in C7–26) |
| A Phase II, randomized, open-label trial of lenalidomide/dexamethasone with or without Elo in subjects with previously untreated MM in Japan (NCT02272803) | Phase II | Newly diagnosed MM | ORR | Arm A: lenalidomide PO 25 mg QD on D1–21+ dexamethasone PO 28 mg and IV 8 mg once daily on D1, 8, 15, 22 (C1–2); D1, 15 (C3–18); D1 (C19 and beyond), PO 40 mg QD on D8, 22 (C3–18); D8, 15, 22 (C19 and beyond) + Elo IV 10 mg/kg, weekly on D1, 8, 15, 22 (C1, 2); D1, 15 (C3–18), Elo IV 20 mg/kg, D1 (C19 and beyond). Repeat every 28 days until subject meets criteria for discontinuation of study drug Arm B: lenalidomide PO 25 mg QD on D1–21+ dexamethasone PO 40 mg weekly on D1, 8, 15, 22. Repeat every 28 days until subject meets criteria for discontinuation of study drug |
| A Phase II single-arm study of Elo in combination with pomalidomide and low-dose dexamethasone (EPd) in patients with MM relapsed or refractory to prior treatment with lenalidomide (NCT02612779) | Phase II | RRMM patients who have received ≥1 but no more than 2 prior lines of therapy, including ≥2 cycles of lenalidomide | PFS | Elo + pomalidomide + low-dose dexamethasone (EPd) |
Note:
a
High-risk MM is defined by GEP70, t(14;16), t(14;20), del(17p) by FISH or cytogenetics, primary plasma cell leukemia, serum LDH ≥2 times of institutional upper limit of normal value.
Abbreviations: MM, multiple myeloma; RRMM, relapsed/refractory MM; PFS, progression-free survival; IV, intravenously; D, days; C, cycles; ORR, overall response rate; SC, subcutaneously; ASCT, autologous stem cell transplantation; PR, partial response; Elo, elotuzumab; IMiD, immuno modulatory drug; VRD, velcade, revlimid, dexamethasone; FISH, fluorescence in situ hybridization; LDH, lactate dehydrogenase; PO, by mouth; QD, every day.