Karyopharm's XPO1 maintenance trial in endometrial cancer nears its PFS readout
XPORT-EC-042 is the only Phase 3 test of an XPO1 inhibitor in TP53 wild-type endometrial cancer, placing selinexor's maintenance benefit against placebo with no in-class precedent to benchmark against.
Executive Summary
- Karyopharm's Phase 3 maintenance trial in TP53 wild-type endometrial cancer is heading toward a progression-free survival readout after finishing enrollment and closing recruitment this spring.
- No other industry-sponsored trial pairs an XPO1 inhibitor with this specific endometrial cancer population, so the result will be the first randomized evidence on whether this mechanism has a maintenance role here.
- The trial's primary completion date has moved twice since 2023, stretching by roughly two years from its original target, even as enrollment and trial status have tracked normally toward completion.
- A placebo-controlled, single-primary-endpoint design means the coming readout can produce a decision-grade signal on maintenance benefit rather than a directional or exploratory one.
The trial
XPORT-EC-042 (NCT05611931) tests selinexor, an oral XPO1 inhibitor already approved as Xpovio in multiple myeloma and lymphoma, as maintenance therapy after platinum-based chemotherapy in adults with TP53 wild-type, advanced or recurrent endometrial carcinoma. The trial randomizes patients to selinexor or placebo across a single experimental arm and a single placebo comparator arm, with investigator-assessed progression-free survival per RECIST v1.1 as the sole primary endpoint. Enrollment reached 257 patients across sites in the United States, Spain, Australia and Italy. The design supports a clean read: one primary endpoint, randomized allocation, and a placebo control. NCT05611931Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial CarcinomaNCT05611931
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
Timing and status
The trial's primary completion date has moved from June 2024 to January 2025 and then to August 2026, a cumulative delay of about two years from its first registered target. Enrollment also grew from 220 to 276 patients in October 2025 before settling at 257 when the trial closed to new patients and moved to Active, not recruiting status on May 29, 2026. That enrollment path, ending close to where it started after a temporary increase, reflects a routine adjustment rather than an operational shortfall; the trial reached its target population and stopped recruiting on schedule with its most recent guidance. Karyopharm has publicly guided to a topline readout in the second half of 2026, a window that contains the registry's own primary completion date. NCT05611931+1Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial CarcinomaNCT05611931Registration Momentum Builds Across the Oncology PipelineFeb 17, 2026
The competitive frame
No other industry-sponsored trial combines an XPO1 inhibitor with TP53 wild-type endometrial cancer, making XPORT-EC-042 the only Phase 3 asset in this specific target-indication pairing. The nearest trials sharing selinexor's target, in myelofibrosis, multiple myeloma and diffuse large B-cell lymphoma, test different diseases and different treatment settings, so they inform selinexor's tolerability profile more than they set an efficacy bar for maintenance PFS in this population. Within endometrial cancer itself, several late-stage programs are testing different mechanisms entirely, including antibody-drug conjugates targeting TROP-2 and B7-H4 and a PD-1 checkpoint inhibitor, none of which share selinexor's mechanism. With no validated XPO1-directed precedent in this indication, a progression-free survival benefit over placebo that holds up under blinded independent central review, one of the trial's eight secondary endpoints, would be the result that establishes whether nuclear-export inhibition has a maintenance role here. NCT05611931Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial CarcinomaNCT05611931
What the readout will test
Selinexor already carries an FDA-approved profile in multiple myeloma and lymphoma under the brand Xpovio, so this readout is not a first-in-human safety question but a test of whether the same mechanism extends progression-free survival when used as maintenance in a different tumor type and a different treatment setting. The trial's eight secondary endpoints, including overall survival, time to next treatment, and quality-of-life measures, will matter for how durable and tolerable any PFS benefit proves to be even if the primary endpoint result is positive. NCT05611931Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial CarcinomaNCT05611931
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.