Table 1 Clinical trials of non-immunotherapies
Agent | Frontline | Relapsed and refractory | |||||
|---|---|---|---|---|---|---|---|
Phase 1 | Phase 2 | Phase 3 | Phase 1 | Phase 2 | Phase 3 | ||
Proteasome inhibitors | Carfilzomib (K) |  |  | ENDURANCE (NCT01863550): KRD versus VRD, similar PFS, 34.6 mon versus 34.4 mon, increased toxicity | NCT01998971: DKD (ORR 84%) | X-171-003-A1 (NCT00511238): single arm, ORR 23.7%, mOS 15.6 mon | 1. ASIPRE (NCT01080391): KRD versus RD, better ORR (87.1 vs. 66.7%, p < 0.001), PFS (26.3 mon vs. 16.7 mon, p = 0.001) and 2-year OS (73.3% vs. 65.0%, p = 0.04) |
| Â | Â | Â | Â | Â | Â | Â | 2. ENDEAVOR (NCT01568866): KD versus RD, better PFS (18.7 vs. 9.4 mon), ORR (77% vs. 63%), VGPR (54.3% vs. 26.8%) and CR (12.5% vs. 6.2%) |
| Â | Ixazomib | Â | Â | 1. TOURMALINE-MM3 (NCT02181413): Ixazomib versus placebo, better median PFS (26.5 mon vs. 21.3 mon) | Â | Â | 1. TOURMALINE-MM1 (NCT01564537): IRD versus RD, better PFS (20.6 mon vs. 14.7 mon), similar AEs |
| Â | Â | Â | Â | 2. TOURMALINE-MM4 (NCT02312258): Ixazomib versus placebo, better median PFS (17.4 mon vs. 9.4 mon), better TTP (17.8 mon vs. 9.6 mon), similar AEs (91% vs. 82%) | Â | Â | 2. NCT01564537: IRD versus RD, better PFS (6.7 mon vs. 4.0 mon) and median OS (25.8 mon vs. 15.8 mon) |
| Â | Â | Â | Â | 3. TOURMALINE-MM2 (NCT01850524): IRD versus RD, ongoing | Â | Â | Â |
| Â | Â | Â | Â | 4. US MM-6: switching from BTZ-based to Ixazomib-based, similar ORR (62% vs. 65%), improved CR rate (4% to 22%) | Â | Â | Â |
|  |  |  |  |  |  |  | 2. OPTIMISMM(NCT 01,734,928): Pom + TZ + DEX versus BTZ + DEX, better PFS (11.2 mon vs. 7.1 mon) |
|  |  |  |  |  |  |  | 3. PomDe + CTX versus PomD: better ORR (64.7% vs. 38.9%) |
Alkylating Agents | Bendamustine |  | Ben + BTZ + DEX (BBD): Overall response 91%, CR 9% | BenP versus MP: better CR (32% vs. 13%) | Ben + Ixazomib + DEX: VGPR 11%, PR 50%, mPFS 5.2 mon, OS 23.2 mon |  |  |
Bcl-2 inhibitors | Venetoclax |  |  |  | NCT01794507: Ven + BTZ + DEX: ORR 67%, VGPR 42% | 1. STORM (NCT02336815): single arm, ORR 21% | 1. BELLINI (NCT02755597): Ven + BTZ + DEX versus BTZ + DEX, suspended (safety issue) |
|  |  |  |  |  |  | 2. NCT02899052: Ven + KD, single arm, ORR 78%, VGPR 56% | 2. CANOVA (NCT03539744): Ven + DEX versus Ven + Pom + DEX, ongoing |
XPO-1 inhibitors | Selinexor |  |  |  | STOMP (NCT02343042): SVD, ORR 63%, median PFS 9 mon | STORM (NCT02336815): Sd, ≥ PR 26%, mDOR 4.4 mon, median PFS 3.7 mon, and mOS 8.6 mon | BOSTON (NCT03110562): SVD versus VD, better PFS (13.93 mon versus 9.46 mon), ORR (76.4% versus 26.3%) |
Kinesin spindle protein inhibitors | Filanesib |  |  |  |  | (NCT00821249: Filanesib vs. Filanesib + DEX, similar PR rate (16% vs. 15%) |  |
| Â | Melflufen | Â | Â | Â | Â | 1. HORIZON (NCT02963493): single arm, ORR 30%, VGPR 11%, PR 18%, CBR 40% | Â |
|  |  |  |  |  |  | 2. O-12-M1 (NCT01897714): Melflufen + DEX, ORR 31%, CBR 49% |  |