Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and Clinical Activity of SX-682 in Combination With BinTrafusp Alfa (M7824 or TGF-beta "Trap"/PD-L1) With CV301 TRICOM in Advanced Solid Tumors (STAT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and Clinical Activity of SX-682 in Combination With BinTrafusp Alfa (M7824 or TGF-beta "Trap"/PD-L1) With CV301 TRICOM in Advanced Solid Tumors (STAT) (NCT04574583), a non-randomized phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicities (DLT).

2. Clinical Question

3. Trial Design

STAT was a Phase I/II, sequential, nonrandomized trial sponsored by the National Cancer Institute. The registry lists the study as completed, with enrollment of 12. It began on 2020-11-24, and the primary completion date was 2023-02-07. No masking was used.

The treatment plan combined SX-682 with bintrafusp alfa and BN-CV301. The arm descriptions characterize a period of SX-682 monotherapy followed sequentially by combination treatment with bintrafusp alfa and BN-CV301. The descriptions identify dose-level groups, but some dose details in the group titles and descriptions do not align. The registry record does not report enough information to resolve that inconsistency, so those details should not be used to reconstruct a definitive dosing sequence.

The brief summary describes screening under a separate protocol and follow-up procedures that could include tumor biopsies, physical examinations, laboratory tests, electrocardiograms, and imaging. Bintrafusp alfa was administered intravenously, BN-CV301 vaccines were injected, and SX-682 was taken by mouth twice a day. The summary states that study drugs could be taken for up to 2 years.

Because allocation was nonrandomized and the groups were sequential dose-level groups, they do not form a randomized comparative experiment. Dose-level observations may inform description of tolerability in the enrolled participants, but differences between groups can also reflect characteristics of the participants, timing, or other factors. The registry record does not report a randomization procedure, a control arm, or a detailed statistical analysis plan.

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: The trial never reached the point of enrolling to phase 2. It stopped early before maximum tolerated dose (MTD) was reached.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Dose Limiting Toxicities (DLT), measured over DLT observation period (first 4 weeks).

The primary endpoint is the number of dose-limiting toxicities, or DLTs, during the first 4 weeks of treatment. The registry defines a DLT as a qualifying adverse event that occurs within 28 days after study therapy begins and is considered possibly attributable to study drugs by the investigator. The definition uses CTCAE v5.0 severity grading and includes specified severe events, with stated exceptions for some events that resolve or can be managed conservatively. It also includes a QTcF threshold of 501 msec or a change from baseline exceeding 60 msec, and unexpected toxicities from the combination that would not be expected with individual agents alone.

In early-phase treatment research, a DLT count is used to describe acute tolerability within a defined observation window. It can help investigators assess whether toxicities meeting the protocol definition occurred during initial treatment. It is not a complete measure of every adverse event, later toxicity, or clinical benefit. Its interpretation depends on the exact definition, the observation window, attribution decisions, and how many participants were evaluable for the endpoint.

The registry record does not report a numerical DLT result or an analysis estimate for this endpoint. Therefore, the endpoint definition can be described, but its observed frequency cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. STAT is listed as a Phase I/II, sequential, nonrandomized trial with no masking. Random allocation helps make treatment groups comparable, on average, with respect to factors that could affect outcomes. Since this trial did not use random allocation, its dose-level groups should be read as descriptive groups rather than interchangeable treatment arms in a controlled comparison. Even when observed counts differ, the design does not isolate treatment effect from differences in participant characteristics or other influences.

What does a DLT count represent?

A count records how many qualifying events were reported under the endpoint definition. The definition sets a limited observation window and requires investigator attribution of possible relationship to study drugs. It also specifies event types and severity criteria. These rules make the endpoint more focused than a count of every symptom or adverse event, but they also mean that the result depends on classification and attribution. An event outside the window, or an event not meeting the definition, would not count as a DLT under this endpoint.

The registry record does not report a DLT result. It therefore does not permit calculation or interpretation of an observed DLT rate. A rate would require both a qualifying event count and the relevant evaluable denominator; neither should be inferred from the general enrollment number alone. In early-phase studies, it is also important to distinguish participants enrolled from participants who completed the DLT observation period, since the registry record does not report endpoint evaluability.

How should uncertainty be understood?

A confidence interval is a range of values generated by a statistical procedure to show the uncertainty around an estimate. In general, narrower intervals indicate greater precision under the assumptions of that procedure, while wider intervals indicate less precision. This general explanation does not describe an interval from STAT: the registry record reports no analysis estimate or confidence interval for the primary endpoint.

For small descriptive groups, counts can change noticeably with the experience of an individual participant. This is a general feature of sparse data, not a new estimate for this trial. A count by itself also does not convey uncertainty or establish whether an apparent difference is compatible with chance variation. The nonrandomized, sequential design adds further limits to interpretation because group differences may have explanations other than dose or treatment.

What does nonrandomized allocation mean for comparisons?

In a randomized trial, allocation is determined by a chance process, which supports a causal comparison when the study is otherwise appropriately conducted and analyzed. In a nonrandomized trial, treatment assignment can be associated with participant characteristics, clinical decisions, or the sequence in which groups are enrolled. Those factors can influence outcomes. Statistical adjustment may sometimes address measured differences, but it cannot automatically remove unmeasured differences. The registry record does not report an adjusted comparative analysis, and it reports no analyses at all.

The group safety counts are therefore best read as descriptions within each listed group. They do not supply a treatment-effect estimate, and they do not support ranking the groups as safer or more effective. The registry itself notes that the arms are not a like-for-like control comparison.

What do planning calculations mean?

A sample-size calculation is a planning exercise that asks how many participants or events a future study might require under specified assumptions. The planning illustration associated with the posted material assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers fractions of an observed effect. For time-to-event outcomes, it expresses planning in total events, while other outcomes use participants per arm. These are design assumptions, not evidence that the trial used those methods.

Planning illustrations based on an observed effect do not show the probability that the completed study detected an effect. That probability is often called observed power when it is calculated after seeing the results, but such a calculation is not a substitute for an estimate and its uncertainty. Here, the registry record does not report the primary effect estimate needed to interpret such a calculation, and a nonrandomized dose-level comparison is not equivalent to the assumed equal-allocation comparison.

More broadly, a p-value, when reported, measures how compatible data are with a specified statistical model and null hypothesis; it is not the probability that the null hypothesis is true. No p-value or model-based comparison is reported for STAT in the registry record. Statistical significance, even if reported, would not by itself resolve design limitations or establish clinical importance.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including disease control rate, progression-free survival, and pharmacokinetic and pharmacodynamic profiles. When a study examines multiple outcomes or makes multiple statistical tests, the chance of at least one apparently notable result can increase. Statistical plans may address this through outcome prioritization or other multiplicity procedures. The registry record does not report a multiplicity strategy, an order of confirmatory testing, or adjusted results. It also reports zero analyses, so no outcome-specific estimates or tests are available to evaluate.

Missing-data handling is not reported in the registry record. The record does not describe how incomplete outcome assessments, missed visits, withdrawal, or unavailable measurements were handled. It also does not report whether participants who did not complete the DLT observation period were included in an endpoint analysis. Those details matter because missingness can affect the interpretation of counts and estimates, especially when the reasons for missing information are related to health or treatment experience.

The analysis populations are not reported in the registry record. It is therefore unclear which enrolled participants were considered eligible for each outcome analysis, whether there was a separate safety population, or how evaluability was defined for the primary endpoint. The enrollment figure should not be treated as the denominator for every outcome without an explicit analysis population.

These omissions limit reproducibility and make it difficult to determine how the outcomes were analyzed. They do not establish that a particular method was or was not used in practice; the registry record does not report the relevant details.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (33.3%), esophageal hemorrhage (33.3%), respiratory, thoracic and mediastinal disorders - other, covid-19 infection (33.3%), upper gastrointestinal hemorrhage (33.3%), disease progression (16.7%).

The safety record reports, by dose-level group, counts at risk and affected for serious and other adverse events, plus deaths. In the group labeled Dose Level 1, serious events affected 1 of 3 at risk, other events affected 3 of 3, and deaths were reported for 1 participant. In the group labeled Dose Level 2, serious events affected 3 of 6 at risk, other events affected 6 of 6, and deaths were reported for 3 participants. In the group labeled Dose Level 3, serious events affected 1 of 3 at risk, other events affected 3 of 3, and deaths were reported for 2 participants.

These are descriptive registry counts. They do not establish that study treatment caused an event or death, and the record does not provide enough detail in these counts to determine timing, duration, recurrence, or attribution. The listed serious-event terms include anemia, esophageal hemorrhage, COVID-19 infection, upper gastrointestinal hemorrhage, disease progression, and hematuria. Term-level percentages should not be read as a complete clinical account or as a comparison between treatment groups. Serious adverse events are not equivalent to DLTs, which follow the trial’s specific definition and observation window.

12. What the Result Does, and Does Not, Mean

The registry record documents a small, nonrandomized Phase I/II study of SX-682 with bintrafusp alfa and BN-CV301 in advanced solid tumors. It describes a dose-limiting toxicity endpoint and reports safety counts for the listed dose-level groups. Those counts provide a limited descriptive view of events recorded in the groups, but they are not estimates from a randomized comparison.

The primary endpoint result is not reported in the registry record. Nor does the record report analysis estimates for the secondary outcomes it names. Consequently, the posted information cannot establish the frequency of DLTs, the size or precision of a clinical outcome effect, or a relationship between treatment and the reported safety events. The counts should not be interpreted as evidence that the regimen does or does not provide clinical benefit.

Even a complete set of numerical outcomes would need to be interpreted in light of the design. Nonrandomized sequential groups can differ for reasons beyond the assigned dose level, and the registry does not report an adjusted comparative analysis. Safety counts also do not provide the same information as an efficacy estimate, and events reported as serious are not automatically DLTs.

The defensible conclusion is therefore narrow: the registry describes the treatment sequence, endpoint definition, and group-level safety counts, but does not provide primary or secondary analysis results. The record cannot answer the treatment-effect question with a precise estimate. It also cannot support causal conclusions from the observed group counts.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines early-phase dose evaluation with a complex treatment sequence in advanced solid tumors. Its primary endpoint is a defined count of dose-limiting toxicities during an early observation period, rather than a direct comparative measure of tumor response. That distinction matters: an endpoint focused on acute tolerability answers a different question from disease control or progression-free survival.

The sequential, nonrandomized design also shapes what the data can establish. Dose-level groups can be described, but they are not randomized controls. Group counts may be useful as a record of what was observed, while remaining insufficient for a causal comparison. This is an important distinction for readers who may otherwise treat adjacent dose groups as if they differed only in dose.

The record names additional clinical and laboratory outcomes, including disease control, progression-free survival, and pharmacokinetic and pharmacodynamic profiles. Those outcomes could address different aspects of treatment evaluation, but the registry record reports no analysis estimates. The contrast between a broad outcome list and the absence of reported analyses is itself relevant to interpretation: a planned or named measure is not the same as a posted result.

Finally, the record illustrates why endpoint definitions and analysis details matter in early-phase research. A DLT depends on a specified event definition, timing window, and attribution rule. Without a reported endpoint count, analysis population, and handling of missing information, readers cannot determine how fully the endpoint was observed or how precise any estimate might be. The trial is therefore most informative statistically as an example of the limits of interpreting nonrandomized safety counts when analysis results are not reported.

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 most direct limitation is that the registry record reports no analysis results, despite identifying a primary endpoint and several secondary outcomes. The primary DLT count is not reported, and no estimates or uncertainty intervals are available for the named outcomes. This prevents assessment of outcome magnitude and precision.

The enrollment was 12, and the safety counts are divided among nonrandomized sequential dose-level groups. Small descriptive groups provide limited information about variability, and the design does not support a like-for-like control comparison. The group counts should not be treated as comparative treatment effects.

The registry record does not report analysis populations, endpoint evaluability, missing-data methods, or a multiplicity strategy. It also does not report a detailed statistical analysis plan or adjusted analyses. These missing details restrict assessment of how outcome data were selected, handled, and tested.

There are inconsistencies between some dose-level group titles and their descriptions. The record does not report a resolution, so the precise dosing details should be interpreted cautiously. Finally, listed serious adverse-event terms and counts do not establish causality, timing, or whether terms overlap within participants. These limitations are specific to interpreting the registry information and do not determine what may be available outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and Clinical Activity of SX-682 in Combination With BinTrafusp Alfa (M7824 or TGF-beta "Trap"/PD-L1) With CV301 TRICOM in Advanced Solid Tumors (STAT) — NCT04574583.
• Registry record last updated 2025-02-03; status last verified 2025-01.
• Results first posted 2023-05-03.
• 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.

18. Record Summary

NCT04574583 is a completed Phase I/II, sequential, nonrandomized trial sponsored by the National Cancer Institute. It enrolled 12 participants and evaluated SX-682 in sequence with bintrafusp alfa and BN-CV301 in advanced solid tumors. The primary endpoint was the number of dose-limiting toxicities during the first 4 weeks of treatment. The registry record includes group-level safety counts but reports zero analyses, including no numerical result for the primary endpoint. It does not provide analysis estimates for the secondary outcomes it lists. Because allocation was nonrandomized and the groups were not like-for-like controls, the posted safety counts are descriptive and do not establish causal differences between groups.