This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Selinexor and Pembrolizumab for the Treatment of Cisplatin-Ineligible or Cisplatin-Refractory Locally Advanced or Metastatic Urothelial Carcinoma (NCT04856189), a na phase 1, phase 2 study. The primary outcome is Recommended Phase 2 Dose (RP2D) (Phase Ib).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04856189 |
| Phase | Phase 1, Phase 2 |
| Condition | Advanced Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mamta Parikh |
| Results posted | Yes |
2. Clinical Question
Population
Patients with locally advanced or metastatic urothelial carcinoma who were not eligible to receive cisplatin or whose disease had worsened after cisplatin. The registry record lists these groups as the intended population; it does not report further eligibility details in the registry record for this analysis.
Intervention
Selinexor plus pembrolizumab. The treatment description specifies oral selinexor on days 1, 8 and 15 and intravenous pembrolizumab over 30 minutes on day 1. Cycles were planned to repeat every 21 days for 24 months unless disease progression or unacceptable toxicity occurred.
Comparator
There was no separate control group in the registry record. The study is listed as single-group, with allocation not applicable and no masking. Its results therefore describe the treated group; they do not provide a like-for-like comparison with another treatment or with usual care.
Primary question
The primary outcome asks for the recommended Phase 2 dose of selinexor during Phase Ib, defined using dose-limiting toxicities. It is a dose-finding question rather than a comparison of treatment effects. The registry record says 3 patients treated at dose level 1 were evaluable before termination, but an RP2D result is not reported in the registry record.
3. Trial Design
This was a Phase Ib/II study of selinexor plus pembrolizumab in patients with advanced urothelial carcinoma who were ineligible for cisplatin or whose disease was cisplatin-refractory. The registry lists a single-group model, no masking and allocation as not applicable. Thus, the study was not designed as a randomized, masked comparison between treatment groups.
The treatment group received selinexor by mouth on days 1, 8 and 15, with pembrolizumab given intravenously over 30 minutes on day 1. Cycles were scheduled every 21 days, for up to 24 months, unless disease progressed or unacceptable toxicity occurred. These are the planned treatment instructions in the registry record; they do not establish how long any participant actually received treatment.
The study began on 2021-04-08, had a primary completion date of 2024-01-04, and is listed as terminated. Enrollment was 4. The record says 3 patients treated at dose level 1 were evaluable for the primary dose-finding outcome before termination. These enrollment and evaluability figures describe different things: enrollment is the record’s overall study count, whereas evaluability refers specifically to the stated primary outcome population.
The primary outcome was the recommended Phase 2 dose, defined by dose-limiting toxicity. Secondary outcomes included the number of patients experiencing a grade 3 or higher adverse event and progression-free survival. The registry record does not report a control group, a completed dose recommendation, or an analysis comparing treatment with an alternative.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Study was terminated prior to patients being enrolled at the second dose level.
Overall Study
| Stage | Treatment (Selinexor, Pembrolizumab) |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: 3 patients treated at dose level 1 were evaluable before study was terminated.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Treatment (Selinexor, Pembrolizumab) |
|---|---|---|
| Participants analysed | 4 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 3 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended Phase 2 Dose (RP2D) (Phase Ib), measured over Up to 2 cycles (each cycle is 21 days); up to about 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg Selinexor |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the recommended Phase 2 dose of selinexor during Phase Ib. The registry defines that dose using dose-limiting toxicities, with toxicities to be listed by dose level. It also describes adverse-event summaries by dose level and expansion cohort, as well as for the total recommended-dose cohort, using event term and grade. Grade is defined as the maximum recorded across a patient’s treatment period.
Dose-finding outcomes serve a different purpose from outcomes that estimate whether a treatment changes disease status or survival. They are intended to guide the dose carried forward for further study by considering toxicity observed at tested dose levels. In general, dose-limiting toxicity provides a structured way to identify adverse effects considered important to dose selection during the specified evaluation period. The registry’s timeframe is up to 2 cycles, each lasting 21 days, or up to about 6 weeks.
The record states that 3 patients treated at dose level 1 were evaluable before the study was terminated. It does not report the dose-limiting toxicity findings by dose level or a selected recommended Phase 2 dose. Consequently, the endpoint definition explains what the study intended to measure, but the registry record does not establish the dose-finding result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a small, single-group study that enrolled 4 participants and was terminated. For the primary dose-finding outcome, it reports that 3 patients treated at dose level 1 were evaluable before termination. These registry entries set the limits on interpretation: the record identifies the planned dose-selection question and the size of the evaluable group, but it does not report the dose-limiting toxicity results or the recommended Phase 2 dose.
Because there was no comparator group, the study cannot provide a direct treatment contrast. Any outcomes recorded for the treatment group are descriptive of those participants and do not show how outcomes would have differed under another intervention. The absence of randomization also means that the registry does not establish balanced treatment groups for a comparative estimate. No comparative effect estimate is reported in the registry record.
The record lists a secondary outcome for grade 3 or higher adverse events and another for progression-free survival. It does not report a progression-free survival estimate, its uncertainty, or a time-to-event analysis. It also does not report the grade 3 or higher adverse-event outcome as a completed result. The serious adverse-event figures describe safety information in the treatment group, but they are not a substitute for the primary dose-finding results or a comparative safety analysis.
The serious-event summary lists 4 participants at risk and 1 affected for serious adverse events; it lists 4 at risk and 4 affected for other adverse events. The record lists 0 deaths. Sepsis and lung infection are each listed among the leading serious adverse-event terms at 25.0%. These are descriptions of what the record reports. They do not establish that the treatment caused an event, indicate how event timing relates to treatment, or measure risk against a control group.
Termination and limited evaluability reduce the scope of conclusions that can be drawn from the record. The reason for termination is not reported in the registry record. The record also does not explain whether the study stopped before planned dose levels or cohorts could be assessed, or whether any results were available outside the registry entry. Without those details, the status alone should not be treated as evidence about efficacy, safety, or the reason the study ended.
Planning calculations based on an observed effect are not observed power and do not turn this single-group record into a comparative trial. Such calculations are hypothetical illustrations under their stated assumptions, not evidence that the trial was designed, conducted, or completed with a particular power. The registry record does not report the trial’s own sample-size justification.
9. Statistical Methods Explained
The registry’s primary outcome is dose-finding, not a treatment-effect comparison. It defines the recommended Phase 2 dose through dose-limiting toxicities and states that these toxicities will be listed by dose level. In general, a dose-finding assessment organizes observed toxicity according to the doses participants received, then uses that information to inform dose selection. The registry record does not report the actual dose-limiting toxicity results, the dose levels assessed beyond the stated dose level 1 group, or the selection rule used to choose a dose.
What does evaluability mean?
For the primary outcome, the record says that 3 patients treated at dose level 1 were evaluable before the study was terminated. Evaluability is outcome-specific: it indicates that participants met the registry’s criteria for being included in that outcome assessment. The criteria themselves are not reported in the registry record. Evaluability should not be treated as a count of all participants enrolled, nor does it establish that a dose recommendation was reached. The registry record reports enrollment of 4 and separately identifies the primary-outcome evaluable group.
How should the toxicity summaries be understood?
The description says adverse events are to be summarized by dose level and expansion cohort, and also for the total recommended-dose cohort. It specifies summaries by event term and grade, with grade defined as the maximum across a patient’s treatment period. In general, a maximum-grade summary retains the highest recorded grade for a participant over the defined period rather than displaying every episode as a separate observation. The record does not report the complete planned summaries, dose-level results, or the details needed to determine how repeated events were handled.
The adverse-event outcome is stated as the number of patients who experience a grade 3 or higher event. This kind of count is a descriptive safety endpoint. It can convey how many participants met the stated event criterion in the assessed group, but a count by itself does not show the event rate over time, severity beyond the stated threshold, or a causal relationship to treatment. The registry’s serious-event summary is a separate safety presentation; the record does not state that it is equivalent to the grade 3 or higher outcome.
What does a single-group design allow?
In general, a single-group study reports outcomes among participants who received the study treatment. Without a comparator, it cannot estimate a treatment contrast against another group within the same trial. A within-group outcome can still be described, but it should not be presented as evidence that treatment changed an outcome relative to an alternative. Here, the registry lists allocation as not applicable, no masking, and a single-group model. The record does not report a randomized or controlled analysis.
Masking, in general, refers to keeping treatment assignment unknown to participants, investigators, or other parties. The registry lists masking as none. It does not describe additional procedures for outcome assessment or the handling of potential observer effects. The allocation entry is not applicable because the design is listed as single-group; the record does not describe assignment between arms.
What can confidence intervals and statistical tests tell readers?
In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical model and its assumptions. A narrower interval indicates greater precision under that model, while a wider interval indicates less precision. A test of statistical significance addresses compatibility of data with a specified null hypothesis under its assumptions; it does not measure clinical importance or establish causation. The registry record does not report a confidence interval, hypothesis test, p-value, or comparative effect estimate for the primary outcome.
The record identifies progression-free survival as a secondary outcome, but does not report a survival estimate or analysis. In general, time-to-event methods account for the timing of an event and can incorporate participants whose event has not been observed by the end of follow-up through censoring. The suitability and interpretation of such methods depend on how follow-up and events are defined and recorded. Those definitions and any analysis details are not reported in the registry record.
Are planning calculations trial results?
General planning illustrations based on an observed effect are not trial outcomes and are not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event planning, the stated quantity is the total number of events; for other outcomes, it is participants per arm. These are hypothetical planning conditions, not a description of this single-group study’s design. The registry record does not report that these assumptions were used to plan the trial or provide its own sample-size justification.
The registry lists no analysis count in the registry record for this interpretation, and no primary-outcome analysis is described. A statistical plan, interim analyses, missing-data procedures, analysis populations, and multiplicity procedures are not reported in the registry record. Without those details or the outcome data, readers cannot assess model choices, precision, robustness, or how analyses were selected.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies a primary dose-finding outcome and secondary outcomes for grade 3 or higher adverse events and progression-free survival. It does not report how the analysis would handle multiple outcomes or repeated statistical tests. In general, multiplicity matters when several hypotheses are tested because the chance of at least one apparently notable result can increase across tests. The record does not state whether any adjustment, hierarchy, or other strategy was planned.
Missing-data procedures are not reported in the registry record. This matters because participants may have incomplete outcome information, and the way missing observations are handled can affect estimates and their interpretation. The registry does not describe the extent or reasons for missing primary or secondary outcome data, whether participants were followed after treatment stopped, or how incomplete follow-up would be addressed.
The primary-outcome population is described as 3 patients treated at dose level 1 who were evaluable before termination. The criteria for evaluability and any broader analysis-population definitions are not reported in the registry record. The record does not explain whether participants who were not evaluable for the primary outcome contributed to safety summaries or other outcomes, so those populations should not be assumed to match.
No interim-analysis plan or statistical analysis plan is reported in the registry record. The record also does not describe how progression-free survival was defined, how censoring was handled, or whether analyses were adjusted for any covariates. These omissions limit assessment of the intended inferential procedures and of how complete or comparable the reported outcome populations may be.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment (Selinexor, Pembrolizumab) | 1 | 4 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Selinexor, Pembrolizumab) | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment (Selinexor, Pembrolizumab) | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Selinexor, Pembrolizumab) |
|---|---|---|
| Sepsis | Infections and infestations | 1 of 4 |
| Lung infection | Infections and infestations | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Selinexor, Pembrolizumab) |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 4 of 4 |
| Fatigue | General disorders | 4 of 4 |
| Anemia | Blood and lymphatic system disorders | 3 of 4 |
| Anorexia | Metabolism and nutrition disorders | 3 of 4 |
| Chills | General disorders | 3 of 4 |
| Hyperglycemia | Metabolism and nutrition disorders | 3 of 4 |
| Lymphocyte count decreased | Investigations | 3 of 4 |
| Nausea | Gastrointestinal disorders | 3 of 4 |
| Neutrophil count decreased | Investigations | 3 of 4 |
| Vomiting | Gastrointestinal disorders | 3 of 4 |
Serious events with the highest arm-level rate: sepsis (25.0%), lung infection (25.0%).
The registry lists 4 participants at risk for serious adverse events and 1 affected. For other adverse events, it lists 4 at risk and 4 affected. It also lists 0 deaths. These are registry counts, not comparative estimates. The record does not provide a control group against which to interpret them.
Sepsis and lung infection are each listed among the leading serious adverse-event terms at 25.0%. Those percentages describe the registry’s presentation of serious-event terms; they should not be read as treatment-attributable risks or as evidence that the treatment caused either event. The record does not report the full event descriptions, timing, duration, resolution, or attribution for these terms. It also does not establish whether an individual could contribute more than one event term.
The serious-event figures should be kept distinct from the secondary outcome defined as the number of patients experiencing a grade 3 or higher adverse event. The record does not report that secondary outcome’s result. Seriousness and grade are different ways of classifying adverse events in general; one should not assume they are interchangeable. With a small treatment group and no comparator, these counts describe what was recorded but do not provide a stable estimate of comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was intended to evaluate selinexor with pembrolizumab in patients with advanced urothelial carcinoma who were ineligible for cisplatin or whose disease was cisplatin-refractory. It describes a single-group Phase Ib/II design, a dose-finding primary outcome, and a planned treatment schedule. It also records enrollment of 4 and termination of the study.
For the primary outcome, the record identifies 3 patients treated at dose level 1 as evaluable before termination. This does not establish that the planned dose-finding question was answered. The dose-limiting toxicity results and the recommended Phase 2 dose are not reported in the registry record. Nor does the record report a progression-free survival result or the grade 3 or higher adverse-event result as a completed outcome.
The safety figures describe serious and other adverse events in the treatment group, including the listed leading serious-event terms and 0 deaths. They do not determine whether an event was caused by treatment, whether the event frequency differs from another treatment, or how the combination compares with no treatment. A single-group record cannot answer those comparative questions on its own.
More broadly, a registry entry records study design and outcome information but does not necessarily include every analysis or detail needed to assess certainty. Here, analysis methods, missing-data procedures, the reason for termination, and the primary dose-finding result are not reported in the registry record. The appropriate interpretation is therefore limited to the stated design, enrollment, evaluability, status, and safety figures, without inferring an efficacy or dose-selection conclusion.
13. Why This Trial Matters Statistically
This study illustrates how a clinical trial can have a primary question that is not a conventional efficacy comparison. Its Phase Ib primary outcome was the recommended Phase 2 dose of selinexor, defined using dose-limiting toxicities. That is a dose-selection objective: the outcome of interest is the toxicity information relevant to choosing a dose for further study, rather than a contrast in clinical outcomes between treatment groups.
The single-group design is important for statistical interpretation. The record reports outcomes and safety information for participants receiving the combination, but it does not include a control group. This distinction prevents descriptive counts from being read as comparative effects. It also highlights why the design, outcome definition, and analysis population should be considered together when interpreting a registry result.
The difference between overall enrollment and outcome evaluability is another useful statistical point. The record reports enrollment of 4 and says 3 patients at dose level 1 were evaluable for the primary outcome before termination. Those figures describe separate aspects of study conduct. They do not by themselves explain why a participant was not evaluable or whether the dose-finding objective was completed.
Finally, the terminated status and absence of a reported dose recommendation show why registry status and results should be read separately. A planned endpoint is not the same as a reported result, and a safety summary is not a substitute for the primary endpoint. The record gives a limited but useful account of what was intended and what is reported, while leaving key outcome and analysis details unreported.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The study’s single-group design is a central limitation for comparative interpretation. There is no control group in the registry record, so the reported safety information cannot establish how the combination compares with an alternative. The record also lists no masking. These design features should be considered when interpreting descriptive outcomes, particularly when no comparative analysis is available.
Enrollment was 4, and the primary-outcome description identifies 3 patients treated at dose level 1 as evaluable before termination. This limited experience leaves little information in the record for characterizing dose-limiting toxicities across dose levels. The registry does not report the dose-level toxicity findings or the recommended Phase 2 dose, so the central dose-finding result cannot be assessed.
The study is listed as terminated, but the reason is not reported in the registry record. The record does not clarify how termination affected planned enrollment, dose escalation, expansion, follow-up, or outcome assessment. It also does not state whether the available outcome data were complete when the study ended.
Several outcome and analysis details are absent. The registry does not report a progression-free survival estimate, a completed grade 3 or higher adverse-event result, the statistical analysis plan, the criteria for evaluability, missing-data procedures, or the analysis populations. It does not report the full timing and attribution details for the listed serious adverse events. These gaps limit assessment of precision, completeness, and the methods used to reach any conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Selinexor and Pembrolizumab for the Treatment of Cisplatin-Ineligible or Cisplatin-Refractory Locally Advanced or Metastatic Urothelial Carcinoma — NCT04856189.
- Registry record last updated 2026-01-29; status last verified 2026-01.
- Results first posted 2026-01-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a Phase Ib/II single-group study of selinexor plus pembrolizumab in cisplatin-ineligible or cisplatin-refractory patients with advanced urothelial carcinoma. The study is listed as open label, with allocation not applicable. Selinexor was planned on days 1, 8 and 15, with pembrolizumab on day 1 of cycles repeating every 21 days for 24 months unless progression or unacceptable toxicity occurred.
The primary outcome was the recommended Phase 2 dose of selinexor, defined by dose-limiting toxicities. The record says 3 patients treated at dose level 1 were evaluable before termination. Overall enrollment was 4, and the study is listed as terminated. The primary dose recommendation, progression-free survival result, and grade 3 or higher adverse-event result are not reported in the registry record.
The serious-event summary lists 1 affected among 4 at risk, with 0 deaths; the other-adverse-event summary lists 4 affected among 4 at risk. Sepsis and lung infection are each listed at 25.0% among leading serious-event terms. The reason for termination and the statistical analysis plan are not reported in the registry record.