Clinical trials of selinexor in other malignancies
| Malignancy . | Study population . | Clinical trial . | Intervention . | Efficacy outcomes . | Toxicity outcomes . | Reference . |
|---|---|---|---|---|---|---|
| MM | Relapsed/refractory (5 prior lines and triple-class refractory) | STORM trial (phase 2b) | Selinexor 80 mg twice weekly plus dexamethasone. | ORR 26%; OS 15.6 mo in patients with at least minimal response vs <2 mo in patients with PD. | Most common grade 3/4: thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%). Most common nonhematologic grade 3/4: nausea (10%) and vomiting (3%). | 77 |
| MM | Relapsed/refractory (1-3 prior lines) | BOSTON trial (phase 3) | Bortezomib, dexamethasone, and selinexor, 100 mg weekly vs bortezomib and dexamethasone alone. | Median PFS 13.9 mo in selinexor arm vs 9.5 mo; ORR 76.4% in selinexor arm vs 62.3%; median OS not reached in selinexor arm. | Most common grade 3/4: thrombocytopenia (39% vs 17%), anemia (16% vs 10%), fatigue (13% vs 1%), and pneumonia (12% vs 10%). | 78 |
| DLBCL | Relapsed/refractory (≥2 lines or not a transplant candidate) | SADAL trial (phase 2) | Selinexor 60 mg twice weekly. | ORR 28%; CR 12%; PR 17%; median PFS 2.6 mo; median OS 9.1 mo; median OS was not reached in patients with PR or better. | Most common grade 3/4: thrombocytopenia (46%), neutropenia (24%), anemia (22%), and fatigue (11%). Most common nonhematologic TRAE were limited to grade 1/2. | 81 |
| NHL | Frontline therapy | Phase 1 | R-CHOP plus selinexor (escalating dose to 100 mg weekly), followed by weekly selinexor maintenance for 1 year. | ORR 100%; CR 90% | Recommended phase 2 dose, selinexor 60 mg weekly. Most common grade 3/4: neutropenia (33%), anemia (17%), fatigue (17%), thrombosis (17%), syncope (17%), hypertension (17%), and supraventricular tachycardia (17%). | 82 |
| AML | Frontline therapy (unfit for intensive therapy) | Phase 1/2 | Azacitidine, venetoclax, and selinexor, 60 mg weekly. | ORR 90% | Most common grade ≥ 3: thrombocytopenia (35%), neutropenia (35%), and infections (15%). | 83 |
| MDS-EB | Frontline therapy | Phase 1b/2 | Sequential azacitidine and selinexor (40 mg weekly, 40 mg twice weekly, or 60 mg weekly). | ORR 78.6%; CR 21%. Patients with mutated TP53: CR in 1 of 3; marrow CR in 2 of 3. | MTD and recommended phase 2 dose remain unknown. Most common TRAE (any grade): neutropenia (93%), anemia (87%), thrombocytopenia (80%), and fatigue (50%). | 84 |
| CLL or NHL | Relapsed/refractory | Phase 1 | Ibrutinib plus selinexor (escalating dose: 40 mg weekly, 30 mg twice weekly). | ORR 32% (CLL 44%, DLBCL 33%, and Richter transformation 11%). Median PFS 8.9 mo in CLL and 2.7 mo in NHL. Median OS 58.9 mo in CLL and 5.1 mo in NHL. | MTD selinexor 40 mg weekly with ibrutinib 420 mg daily. Most common grade ≥ 3: thrombocytopenia (24%), anemia (18%), and neutropenia (12%). | 85 |
| Glioblastoma | Relapsed | Phase 2 | Selinexor 50 mg/m2 twice weekly, 60 mg twice weekly, or 80 mg weekly. | 6-month PFS 17.7% (selinexor 80 mg weekly), 10% (selinexor 50 mg/m2 twice weekly), and 7.7% (selinexor 60 mg twice weekly). Median OS 10.5 mo (selinexor 50 mg/m2 twice weekly), 8.5 mo (selinexor 60 mg twice weekly), 10.2 mo (selinexor 80 mg weekly); 28% of patients with reduction in tumor size. | Most common hematologic TRAE (any grade): thrombocytopenia (43%), neutropenia (26%), and anemia (17%). Most common nonhematologic TRAE (any grade): fatigue (60%), nausea (59%), decreased appetite (43%), vomiting (30%), and hyponatremia (20%). | 86 |
| Dedifferentiated liposarcoma | Relapsed/refractory (2-5 prior lines) | Phase 2/3 | Selinexor 60 mg twice weekly vs placebo. | PFS 2.8 mo in selinexor arm vs 2.1 mo; ORR 2.7% in selinexor arm vs 0%. No difference in OS at median 14.6 mo. | Most common grade 3/4: anemia (19%), hyponatremia (11%), asthenia (10%), and thrombocytopenia (10%). | 87 |
| Pancreatic adenocarcinoma | Frontline therapy (metastatic) | Phase 1b | Gemcitabine, nab-paclitaxel, and selinexor (escalating dose: 60 mg weekly, 80 mg weekly). | PR 40% SD 40% PD 20% | MTD selinexor 60 mg weekly. | 88 |
| Triple-negative breast cancer | Relapsed/refractory (metastatic) | Phase 2 | Selinexor 60 mg twice weekly. | No clinical benefit PD 70% SD 30% PR 0% CR 0% | Most common grade 3/4: thrombocytopenia (10%), fatigue (10%), and dyspnea (10%). | 89 |
| Metastatic castration-resistant prostate cancer | Refractory to abiraterone and/or enzalutamide | Phase 2 | Selinexor 60 mg twice weekly. | PFS not reported, study terminated early; PR 25%; SD 50%; unconfirmed PD 25%. | 21% of patients came off study because of unacceptable tolerability; most common TRAE (any grade): anorexia (86%), nausea (64%), weight loss (50%), fatigue (50%), and thrombocytopenia (50%). | 90 |
| Colorectal cancer | Relapsed/refractory (metastatic, unresectable) | SENTINEL (Phase 1) | mFOLFOX plus selinexor (escalating dose: 40 mg, 60 mg, 80 mg on days 1, 3, and 8 of 2-week cycles). | No relevant clinical activity observed. | MTD not reported; 100% of patients at selinexor 40 mg and 66% at selinexor 20 mg dose had DLTs/withdrew. | 91 |
| Endometrial cancer | Frontline therapy or first relapse with PR/CR to platinum-based chemotherapy | SIENDO (Phase 3) | Maintenance selinexor 80 mg weekly vs placebo. | Median PFS 5.7 mo in selinexor arm vs 3.8 mo; wild-type TP53 subgroup: median PFS 27.4 mo in selinexor arm vs 5.2 mo; PFS improvement remained significant in tumors that were MSS/pMMR. | Most common grade 3/4: neutropenia (18% vs 0%), nausea (12% vs 0%), and thrombocytopenia (9% vs 0%). | 92 |
| Malignancy . | Study population . | Clinical trial . | Intervention . | Efficacy outcomes . | Toxicity outcomes . | Reference . |
|---|---|---|---|---|---|---|
| MM | Relapsed/refractory (5 prior lines and triple-class refractory) | STORM trial (phase 2b) | Selinexor 80 mg twice weekly plus dexamethasone. | ORR 26%; OS 15.6 mo in patients with at least minimal response vs <2 mo in patients with PD. | Most common grade 3/4: thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%). Most common nonhematologic grade 3/4: nausea (10%) and vomiting (3%). | 77 |
| MM | Relapsed/refractory (1-3 prior lines) | BOSTON trial (phase 3) | Bortezomib, dexamethasone, and selinexor, 100 mg weekly vs bortezomib and dexamethasone alone. | Median PFS 13.9 mo in selinexor arm vs 9.5 mo; ORR 76.4% in selinexor arm vs 62.3%; median OS not reached in selinexor arm. | Most common grade 3/4: thrombocytopenia (39% vs 17%), anemia (16% vs 10%), fatigue (13% vs 1%), and pneumonia (12% vs 10%). | 78 |
| DLBCL | Relapsed/refractory (≥2 lines or not a transplant candidate) | SADAL trial (phase 2) | Selinexor 60 mg twice weekly. | ORR 28%; CR 12%; PR 17%; median PFS 2.6 mo; median OS 9.1 mo; median OS was not reached in patients with PR or better. | Most common grade 3/4: thrombocytopenia (46%), neutropenia (24%), anemia (22%), and fatigue (11%). Most common nonhematologic TRAE were limited to grade 1/2. | 81 |
| NHL | Frontline therapy | Phase 1 | R-CHOP plus selinexor (escalating dose to 100 mg weekly), followed by weekly selinexor maintenance for 1 year. | ORR 100%; CR 90% | Recommended phase 2 dose, selinexor 60 mg weekly. Most common grade 3/4: neutropenia (33%), anemia (17%), fatigue (17%), thrombosis (17%), syncope (17%), hypertension (17%), and supraventricular tachycardia (17%). | 82 |
| AML | Frontline therapy (unfit for intensive therapy) | Phase 1/2 | Azacitidine, venetoclax, and selinexor, 60 mg weekly. | ORR 90% | Most common grade ≥ 3: thrombocytopenia (35%), neutropenia (35%), and infections (15%). | 83 |
| MDS-EB | Frontline therapy | Phase 1b/2 | Sequential azacitidine and selinexor (40 mg weekly, 40 mg twice weekly, or 60 mg weekly). | ORR 78.6%; CR 21%. Patients with mutated TP53: CR in 1 of 3; marrow CR in 2 of 3. | MTD and recommended phase 2 dose remain unknown. Most common TRAE (any grade): neutropenia (93%), anemia (87%), thrombocytopenia (80%), and fatigue (50%). | 84 |
| CLL or NHL | Relapsed/refractory | Phase 1 | Ibrutinib plus selinexor (escalating dose: 40 mg weekly, 30 mg twice weekly). | ORR 32% (CLL 44%, DLBCL 33%, and Richter transformation 11%). Median PFS 8.9 mo in CLL and 2.7 mo in NHL. Median OS 58.9 mo in CLL and 5.1 mo in NHL. | MTD selinexor 40 mg weekly with ibrutinib 420 mg daily. Most common grade ≥ 3: thrombocytopenia (24%), anemia (18%), and neutropenia (12%). | 85 |
| Glioblastoma | Relapsed | Phase 2 | Selinexor 50 mg/m2 twice weekly, 60 mg twice weekly, or 80 mg weekly. | 6-month PFS 17.7% (selinexor 80 mg weekly), 10% (selinexor 50 mg/m2 twice weekly), and 7.7% (selinexor 60 mg twice weekly). Median OS 10.5 mo (selinexor 50 mg/m2 twice weekly), 8.5 mo (selinexor 60 mg twice weekly), 10.2 mo (selinexor 80 mg weekly); 28% of patients with reduction in tumor size. | Most common hematologic TRAE (any grade): thrombocytopenia (43%), neutropenia (26%), and anemia (17%). Most common nonhematologic TRAE (any grade): fatigue (60%), nausea (59%), decreased appetite (43%), vomiting (30%), and hyponatremia (20%). | 86 |
| Dedifferentiated liposarcoma | Relapsed/refractory (2-5 prior lines) | Phase 2/3 | Selinexor 60 mg twice weekly vs placebo. | PFS 2.8 mo in selinexor arm vs 2.1 mo; ORR 2.7% in selinexor arm vs 0%. No difference in OS at median 14.6 mo. | Most common grade 3/4: anemia (19%), hyponatremia (11%), asthenia (10%), and thrombocytopenia (10%). | 87 |
| Pancreatic adenocarcinoma | Frontline therapy (metastatic) | Phase 1b | Gemcitabine, nab-paclitaxel, and selinexor (escalating dose: 60 mg weekly, 80 mg weekly). | PR 40% SD 40% PD 20% | MTD selinexor 60 mg weekly. | 88 |
| Triple-negative breast cancer | Relapsed/refractory (metastatic) | Phase 2 | Selinexor 60 mg twice weekly. | No clinical benefit PD 70% SD 30% PR 0% CR 0% | Most common grade 3/4: thrombocytopenia (10%), fatigue (10%), and dyspnea (10%). | 89 |
| Metastatic castration-resistant prostate cancer | Refractory to abiraterone and/or enzalutamide | Phase 2 | Selinexor 60 mg twice weekly. | PFS not reported, study terminated early; PR 25%; SD 50%; unconfirmed PD 25%. | 21% of patients came off study because of unacceptable tolerability; most common TRAE (any grade): anorexia (86%), nausea (64%), weight loss (50%), fatigue (50%), and thrombocytopenia (50%). | 90 |
| Colorectal cancer | Relapsed/refractory (metastatic, unresectable) | SENTINEL (Phase 1) | mFOLFOX plus selinexor (escalating dose: 40 mg, 60 mg, 80 mg on days 1, 3, and 8 of 2-week cycles). | No relevant clinical activity observed. | MTD not reported; 100% of patients at selinexor 40 mg and 66% at selinexor 20 mg dose had DLTs/withdrew. | 91 |
| Endometrial cancer | Frontline therapy or first relapse with PR/CR to platinum-based chemotherapy | SIENDO (Phase 3) | Maintenance selinexor 80 mg weekly vs placebo. | Median PFS 5.7 mo in selinexor arm vs 3.8 mo; wild-type TP53 subgroup: median PFS 27.4 mo in selinexor arm vs 5.2 mo; PFS improvement remained significant in tumors that were MSS/pMMR. | Most common grade 3/4: neutropenia (18% vs 0%), nausea (12% vs 0%), and thrombocytopenia (9% vs 0%). | 92 |
AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CR, complete response; DLBCL, diffuse large B-cell lymphoma; DLT, dose-limiting toxicity; MDS-EB, myelodysplastic syndrome with excess blasts,; MSS/pMRR, microsatellite stable/mismatch repair proficient; MTD, maximum tolerated dose; NHL, non-Hodgkin lymphoma; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; R-CHOP, rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone; SD, stable disease; TRAE, treatment related adverse event.