Table 1.
Summary of important clinical trials with XVd regimens.
| Trial | Design | Median prior therapies (range) | Patients (n) | Regimen/RP2D | Response rates | Toxicities (grade 3–4, ⩾10%) |
|---|---|---|---|---|---|---|
| STOMP (NCT02343042) XVd arm | Phase I/II, multi-arm study | 3 (1–11) | 42 | RP2D: Selinexor 100 mg QW + bortezomib 1.3 mg/m2 QW + dex 40 mg QW | ORR 63%, CBR 80%, mPFS 9 months RP2D: ORR 58%, CBR 79% |
Thrombocytopenia (46%), neutropenia (23%), fatigue (14%), anemia (12%) |
| EudraCT201400244440 (SELVEDEX) | Phase I/II, single-arm study | 45 mg/m2 group: 3 (2–7) 30 mg/m2 group: 3 (1–7) |
11 | Selinexor 45 mg/m2 or 30 mg/m2 QW + bortezomib 1.3 mg/m2 BIW + dex 40 mg QW | 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%) |
| NCT03110562 (BOSTON) | Phase III, open-label study | 2 (1–3) | 402 | 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 | 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%) |
| NCT03589222 (GEM-SELIBORDARA) | Phase II, single-arm, open-label study | Part 1: 3 (2–3) part 2: 1 |
57 | Selinexor 60/100 mg QW + daratumumab 16 mg/kg QW + bortezomib 1.3 mg/m2 QW + dex 40 mg QW | 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%) |
BIW, twice weekly; CBR, clinical benefit rate; mDOR, median duration of response; mOS, median overall survival; mPFS, median progression-free survival; ORR, objective response rate; QW, once weekly; RP2D, recommended phase II dose.