Table 2.
Phase II/III Clinical Trials of XPO1 Inhibitors in Solid Tumors.
| Study/ID | Phase | Disease entity | Regimen | Key outcomes/findings | Reference |
|---|---|---|---|---|---|
| NCT02215161 | II | Prostate cancer (refractory to abiraterone and/or enzalutamide) | Selinexor | Prostate-specific antigen response (≥50% decline): 14%; radiographic response (RECIST): PR 25%, SD 50% | (49) |
| NCT02402764 | II | Triple-negative breast cancer (heavily pretreated; median 2 prior chemotherapy lines) | Selinexor | ORR: 0%; mPFS: 0.92 mo, mOS: 5.98 mo | (50) |
| NCT02025985 | II | Gynecological cancer (heavily pretreated; median prior regimens—ovarian: 6, endometrial: 2, cervical: 3) | Selinexor | DCR (≥12 wk)—total: 30%, ovarian: 30%, endometrial: 35%, cervical: 24%; confirmed PR—ovarian: 8%, endometrial: 9%, cervical: 4% | (51) |
| KING | II | Glioblastoma (recurrence/progression after radiation and temozolomide, KPS ≥60) | Selinexor; arm B: 50 mg/m2 twice weekly; arm C: 60 mg flat dose twice weekly; arm D: 80 mg flat dose once weekly | 6-mo PFS—arm B: 10.0%, arm C: 7.7%, arm D: 17.2%; mOS—arm B: 10.5 mo, arm C: 8.5 mo, arm D: 10.2 mo | (52) |
| NCT03095612 | I/II | KRAS-mutant advanced NSCLC (advanced, previously treated with ≥1 prior line) | Selinexor + docetaxel | ORR: 22%; mPFS—KRASG12C: 4.1 mo, KRASnon-G12C: 4.0 mo | (53) |
| NCT03193437/NCT03466827 | II | Thymoma and thymic carcinoma (progression after ≥1 platinum-containing chemotherapy regimen) | Selinexor | ORR—thymoma: 12.5%, thymic carcinoma: 6.7%; mPFS—thymoma: 13.6 mo, thymic carcinoma: 7.8 mo; mOS—thymoma: not reached, thymic carcinoma: 15.5 mo | (54) |
| SEAL | III | DD-LPS (advanced unresectable; 2–5 prior therapies) | Selinexor (vs. placebo) | mPFS: 2.8 mo vs. 2.1 mo (HR 0.70, p = 0.011); time to next treatment: 5.8 mo vs. 3.2 mo (HR 0.50, p < 0.0001); mOS: 10.0 mo vs. 12.9 mo (HR 1.02, p = 0.54) | (46) |
| SIENDO | III | Endometrial cancer (after response to platinum–taxane chemotherapy) | Selinexor (vs. placebo) | mPFS: 5.7 mo vs. 3.8 mo (HR 0.76, p = 0.126); TP53 wild-type subgroup PFS: 13.7 mo vs. 3.7 mo (HR 0.41, p = 0.002) | (47) |
| NCT05611931 | III | Endometrial cancer (TP53 wild-type advanced or recurrent; CR/PR after ≥12 wk of platinum-based therapy ± immunotherapy) | Selinexor | Ongoing | (48) |
CR: complete response; DCR: disease control rate; DD-LPS: dedifferentiated liposarcoma; HR: hazard ratio; KPS: Karnofsky performance status; ORR: objective response rate; mOS: median overall survival; mPFS: median progression-free survival; NSCLC: non–small cell lung cancer; PFS: progression-free survival; PR: partial response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: stable disease; XPO1: exportin-1.