Karyopharm's Selinexor Trial Cuts Enrollment 58% Ahead of H2 2026 Readout
XPORT-MM-031 shrank from 222 to 117 patients and slipped 41 months on completion timing before its event-driven PFS readout, a backdrop the 91.4% endpoint-met model score does not price in.
Executive Summary
- Karyopharm expects top-line progression-free survival data from XPORT-MM-031, comparing selinexor-based SPd to elotuzumab-based EloPd in relapsed/refractory multiple myeloma, in the second half of 2026. This is the trial's first disclosed efficacy readout.
- Enrollment fell 58% from an original 280-patient plan to 117, and the primary completion date slipped 41 months, from October 2022 to March 2026. Those changes flag a Critical risk score in the dossier's protocol-stability tracking, a pattern investors should weigh against the model's optimistic endpoint read.
- The 91.4% endpoint-met probability carries LOW confidence and rests mainly on phase and endpoint-type base rates rather than trial-specific evidence. This changes how much weight the number should carry on its own.
- Selinexor has one Phase 3 win in myeloma already, the BOSTON trial. But the broader XPO1-in-myeloma landscape shows a 43% historical termination rate across 5 sponsors, meaning the mechanism's overall track record is mixed even where the drug itself has succeeded once.
The catalyst
Karyopharm Therapeutics Inc. expects top-line data from the Phase 3 XPORT-MM-031 (EMN29) trial in multiple myeloma in the second half of 2026 Press ReleasePress ReleaseJan 12, 2026. The trial, registered as NCT05028348, compares selinexor plus pomalidomide plus dexamethasone (SPd) against elotuzumab plus pomalidomide plus dexamethasone (EloPd) in patients who have received one to four prior lines of therapy NCT05028348A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple MyelomaNCT05028348. Its single registered primary endpoint is progression-free survival, an event-driven, time-to-event measure with 9 secondary endpoints covering response rate, overall survival, and quality of life NCT05028348A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple MyelomaNCT05028348. Karyopharm's chief executive Richard Paulson called 2026 "a transformative year" for the company's broader pipeline, though his January 2026 remarks centered on the SENTRY and XPORT-EC-042 trials rather than XPORT-MM-031 specifically Press ReleasePress ReleaseJan 12, 2026.
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
Trial under strain
The registry history behind this readout shows more instability than the topline guidance suggests. Enrollment moved from 280 patients at trial start in 2022, up to 300, down to 222, briefly to 109 in October 2024, back up to 222 days later, and down again to 117 by December 2025, a net 58% reduction from the original plan NCT05028348A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple MyelomaNCT05028348. The primary completion date moved three times, from October 2022 to March 2023, to July 2023, and finally to March 2026, a cumulative slip of 41 months NCT05028348A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple MyelomaNCT05028348. The dossier's protocol-stability tool assigns this trial a Critical risk score of 100 out of 100, citing 9 flagged signals including multiple completion-date changes and enrollment underperformance.
What the model rests on
The endpoint-met probability of 91.4% carries a LOW confidence label, and the driver mix behind it leans on phase-level and endpoint-type historical success rates rather than trial-specific signals [AXL-MODEL]. That basis matters: a score built mainly on how often Phase 3 trials of this endpoint type succeed generally, rather than on this trial's own enrollment trajectory or interim data, is a weaker foundation for confidence than a score anchored in mechanism-specific evidence. The completion probability sits far lower, in a 13% to 33% range, reflecting the operational risk the endpoint score does not price in [AXL-MODEL].
Precedent and competitive frame
Selinexor already has one positive Phase 3 result in this same indication: the BOSTON trial reported a median PFS of 13.93 months versus 9.46 months (HR=0.70, p=0.0075) and an overall response rate of 76.4% versus 62.3% (p=0.0012), published in The Lancet in 2020. That gives the drug a track record, though not proof this specific comparator regimen and patient population will repeat it. As a Selective Inhibitor of Nuclear Export targeting XPO1, selinexor has no other approved drug operating on the same target; the closest comparators in myeloma use different mechanisms entirely, including Cereblon-targeted iberdomide and BCMA-targeted belantamab mafodotin [competitiveContext]. The broader XPO1-in-myeloma landscape carries a 43% historical termination rate across 5 sponsors, a challenging backdrop that tempers how much confidence the mechanism alone should carry.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.