Table 2.
Clinical trials with selinexor in multiple myeloma.
| Trial | Design | Regimen/RP2D | Population | Response rates | Toxicities (grade 3–4, ⩾10%) |
|---|---|---|---|---|---|
| NCT01607892 | Phase I, open-label, single-arm, dose escalation and dose expansion study | Dose escalation: Selinex or 3–60 mg/m2 BIW, dose expansion: Selinexor 45 or 60 mg/m2 BIW + dex 20 mg BIW, RP2D: Selinexor 45 mg/m2 (80 mg) BIW + dex 20 mg BIW | Median 6 prior lines of therapy 25 in dose escalation 59 in dose expansion (n = 84, MM n = 81, WM n = 3) |
Single-agent: ORR 4%, CBR 21% RP2D: ORR 50%, CBR 58% |
Thrombocytopenia (45%), neutropenia (23%), anemia (23%), hyponatremia (26%), fatigue (13%) |
| NCT02336815 (STORM I) | Phase IIb, open-label single-arm study |
Selinexor 80 mg BIW + dex 20 mg BIW | Median 7 prior lines of therapy quad-refractory/penta-refractory disease (n = 79) | ORR 21%, CBR 33%, mDOR 5 months, mPFS 2.3 months, mOS 9.3 months | Thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), fatigue (15%), nausea (8%), diarrhea (5%) |
| NCT02336815 (STORM II) | Phase IIb, open-label, single-arm study | Selinexor 80 mg + dex 20 mg BIW | Triple-class penta-treated MM (n = 123) | ORR 26%, CBR 39%, mDOR 4.4 months, mPFS 3.7 months, mOS 8.6 months | Thrombocytopenia (58%), anemia (44%), hyponatremia (22%), neutropenia (21%), nausea (10%) |
| EudraCT201400244440 (SELVEDEX) | Phase I/II, single-arm study | Selinexor 30 or 45 mg/m2 QW + bortezomib 1.3 mg/m2 BIW + dex 40 mg QW | Median 3 prior lines of therapy (n = 11) | 45 mg/m2 group: ORR 80%, mPFS 17 months, 1 year OS 100%, 2 year OS 75%. 30 mg/m2 group: ORR 67%, 1 year OS 75% | Hyponatremia (18%), polyneuropathy (18%) |
| NCT02199665 (MMRC) | Phase I, single-arm, dose escalation + dose expansion | RP2D: Selinexor 60 mg BIW + carfilzomib 20 or 27 mg/m2 BIW + dex 20 mg BIW | Median 2 prior lines of therapy (n = 21) | ORR 48%, CBR 71%, mPFS 3.7 months, mOS 22.4 months RP2D: ORR 38%, CBR 62%, mPFS 3.5 months, mOS 22.4 months |
Thrombocytopenia (71%), anemia (33%), lymphopenia (33%), neutropenia (33%), infections (24%), fatigue (14%), diarrhea (10%), eye disorders (10%), musculoskeletal disorders (10%), elevated liver enzymes (10%) |
| STOMP (NCT02343042)XVd arm | Phase I/II, multi-arm study | RP2D: Selinexor 100 mg QW + bortezomib 1.3 mg/m2 QW + dex 40 mg QW | Median 3 prior lines of therapy (n = 42) | ORR 63%, CBR 80%, mPFS 9 months RP2D: ORR 58%, CBR 79% |
Thrombocytopenia (46%), neutropenia (23%), fatigue (14%), anemia (12%) |
| STOMP XDd arm | RP2D: Selinexor 100 mg QW + Daratumumab 16 mg/kg QW + dex 40 mg QW | Median 3 prior lines of therapy PI and IMiD refractory patients (n = 34) | ORR 69%, CBR 81%, mPFS 12.5 months, RP2D: ORR 75% | Thrombocytopenia (47%), leukopenia (32.4%), neutropenia (26.5%), lymphopenia (17.6%), fatigue (17.6%), anemia (32.4%), hyponatremia (11.8%) | |
| STOMP XPd arm | RP2D:Selinexor 60 mg QW + pomalidomide 4 mg QD D1-21 + dex 40 mg QW | Median 3 prior lines of therapy (n = 65) | RP2D: ORR 65%, mPFS not reach | Neutropenia (55%), anemia (32%), thrombocytopenia (31%), nausea (2%), fatigue (11%), decreased appetite (2%) | |
| STOMP XKd arm | Selinexor 80 or 100 mg QW + carfilzomib 56 or 70 mg/m2 + dex 40 mg QW | Median 4 prior lines of therapy (n = 32) | ORR 78%, mPFS 15 months, mDOR 22.7 months | Thrombocytopenia (46.9%), anemia (18.8%) | |
| STOMP XRd arm | RP2D: Selinexor 60 mg QW + Lenalidomide 25 mg QD D1-21 + dex 40 mg QW | NDMM and RRMM (n = 32, NDMM n = 8, RRMM n = 24) | Lenalidomide naïve RRMM: ORR 92% NDMM:ORR 100% | RRMM:thrombocytopenia (63%), neutropenia (63%), fatigue (17%), NDMM: thrombocytopenia (38%), neutropenia (75%), fatigue (50%), decreased appetite (13%) | |
| NCT03110562 (BOSTON) | Phase III, open-label study | Selinexor 100 mg QW + bortezomib 1.3 mg/m2 QW + dex 20 mg BIW versus bortezomib 1.3 mg/m2 BIW/QW + dex 20 mg BIW | Median 2 prior lines of therapy (n = 402) | ORRs 76.4% versus 62.3%, mPFS 13.93 versus 9.46 months, mDOR 20.3 versus 12.9 months, mOS not reach versus 25 months | XVd versus Vd: thrombocytopenia (39% versus 17%), fatigue (13% versus 1%), anemia (16% versus 10%), pneumonia (12% versus 10%) |
| NCT03944057 (MARCH) | Phase I, single-arm study | Selinexor 80 mg BIW + dex 20 mg BIW | Median 6 prior lines of therapy refractory to IMiD and PI (n = 82) | ORR 29.3% mPFS 3.7 months mOS 13.2 months mDOR 4.7 months | Anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.3%), hyponatremia (29.3%), lung infection (25.6%), hypokalemia (12.2%), asthenia (9.8%) |
| NCT02831686 | Phase I, single-arm study | Selinexor (cohort A: 40/60 mg BIW; cohort B: 80/100 mg QW) + ixazomib 4 mg QD D1,8,15) + dexamethasone (given with selinexor) | Median 5 prior lines of therapy (n = 18) | ORR 22% | Thrombocytopenia (61.1%), neutropenia (27.8%), anemia (16.7%) nausea (11.1%), vomiting (11.1%), syncope (11.1%), fatigue (11.1%), hyperglycemia (11.1%) |
| NCT02186834 | Phase I/II, single-arm study | Selinexor 80 mg QW/BIW + liposomal doxorubicin 20 mg/m2 D1 + dex 40 mg QW/BIW | Median 6 prior lines of therapy (n = 27) | ORR 15%, CBR 26% | Thrombocytopenia 33%, neutropenia 33%, hyponatremia 30%, anemia 26%, nausea/vomiting 11%, hyperglycemia 11% |
| NCT02780609 | Phase I/II, dose escalation | Selinexor 80 mg D-3,-2 + melphalan 100 mg/m2 IV D-3,-2 | Patients achieving PR or VGPR after less than four lines of chemotherapy (n = 22) | ORR 91.7% | Febrile neutropenia (25%) |
| ALLG MM23 SeaLAND | Phase III, open-label study | Selinexor 40 mg QW (60 mg QW from cycle 2, 15 mg QD from cycle 4) + lenalidomide 10 mg QD D1–21 versus lenalidomide 10 mg QD D1–21 | Patients underwent ASCT (n = 290) | Not given | Not given |
| NCT03589222 (GEM-SELIBORDARA) | Phase II, single-arm, open label study | Selinexor 60/100 mg QW + daratumumab 16 mg/kg QW + bortezomib 1.3 mg/m2 QW + dex 40 mg QW | Part 1 patients with ⩾3 prior lines of therapy part 2, patients in relapse or with progressive disease after ⩾1 prior lines of therapy (n = 57) |
Part 1: ORR 50%, mPFS 7.1 months, mOS 27.5 months part 2: ORR 82%, mPFS and mOS not reach |
Thrombocytopenia (34%), neutropenia (25%) |
ASCT, autologous stem cell transplantation; CBR, clinical benefit rate; IMiD, immunomodulatory drugs; mDOR, median duration of response; mOS, median overall survival; MM, multiple myeloma; mPFS, median progression-free survival; NDMM, newly diagnosed MM; ORR, objective response rate; PI, proteasome inhibitor; RP2D, recommended phase II dose; VGPR, very good partial response; WM, Waldenstrom macroglobulinemia.