NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (NCT04332653), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1b: Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), Trial Treatment-related TEAEs and Trial Treatment-related SAEs.

2. Clinical Question

3. Trial Design

This is an open-label Phase 1b/2a study of NT-I7 in combination with pembrolizumab in participants with relapsed or refractory advanced solid tumors. The registry lists non-randomized allocation, no masking, and a sequential model. Registry enrollment is 215. The record gives a study start of 2020-06-10, primary completion of 2024-11-22, and a completed status.

Phase 1b was a dose-escalation stage. NT-I7 was scheduled on Day 1 of alternate 21-day cycles, while pembrolizumab was scheduled on Day 1 of every 21-day cycle. The intended dose-escalation objectives were safety and tolerability and identification of a maximum tolerated dose and/or recommended Phase 2 dose. The Phase 1b groups listed for the safety outcome are dose levels of 480 ug/kg, 960 ug/kg, and 1200 ug/kg of NT-I7.

Phase 2a included cohorts defined by tumor type and checkpoint inhibitor history: checkpoint inhibitor-treated triple negative breast cancer, non-small cell lung cancer, and small cell lung cancer; and checkpoint inhibitor-naïve microsatellite stable colorectal cancer and pancreatic cancer. Expansion cohorts were also listed for colorectal and pancreatic cancer. A biomarker cohort concerned checkpoint inhibitor-naïve ovarian cancer and the potential correlation between tumor-infiltrating lymphocytes and clinical benefit. The registry describes the combination in all these cohorts; it does not describe a randomized comparison against pembrolizumab alone or another control.

The registry lists 11 outcome measures, including safety outcomes and secondary measures such as duration of objective response, disease control rate, progression-free survival, overall survival, and anti-drug antibodies. The study's intended objectives and listed outcomes should be distinguished from reported results: efficacy estimates and the detailed statistical analysis plan are not reported in the registry record.

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 consisted of a dose escalation phase (Phase 1b) followed by a dose expansion phase (Phase 2a) and a Biomarker Cohort.

Only the first 6 of 11 groups are shown.

Phase 1b

Reasons for not completing this period:

Phase 2a

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: all participants who received at least one dose (even partially) of one or both trial medications. Only participants in Phase 1b were analyzed for this Outcome Measure.

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.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1b: Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), Trial Treatment-related TEAEs and Trial Treatment-related SAEs, measured over Up to 2 years and 3 months.

The primary outcome is a count of participants in Phase 1b who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), trial treatment-related TEAEs, and trial treatment-related SAEs. It is a participant-level safety outcome: the question is how many participants experienced events in each stated category, not how many total event episodes occurred.

The registry defines a TEAE as an adverse event that begins on or after the first day of trial treatment, or worsens on or after that day, within the stated post-treatment window. That window extends up to 30 days after the last dose of trial drugs or initiation of new anticancer therapy, whichever is earlier; for SAEs, it extends up to 90 days. A serious adverse event is defined by specified consequences, including death, a life-threatening event, inpatient hospitalization or prolonged hospitalization, persistent or significant incapacity, a congenital anomaly or birth defect, or an important medical event judged to require intervention to prevent such outcomes.

Safety counts are useful in dose-escalation work because they describe the observed burden of adverse events and serious events in participants exposed to the study drugs. They also provide context for considering tolerability and dose selection. Counts alone do not establish that the study drugs caused an event, nor do they quantify the event's severity beyond the registry's categories. The registry's primary outcome population is the Safety Analysis Set: participants who received at least one dose, even partially, of one or both trial medications. Only Phase 1b participants were analyzed for this primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

For a binary safety outcome, each participant is classified according to whether the event occurred during the defined observation period. A count such as 2 participants with serious adverse events among 3 at risk describes the number meeting the event definition and the group denominator. It does not count repeated episodes. One participant with several events can still contribute one participant to a participant-level count. The registry's primary outcome is expressly a count of participants.

General statistical explanation: a proportion can be estimated by dividing the event count by the number at risk, and uncertainty around that estimate can be expressed with a confidence interval. No new proportions or confidence intervals are calculated in this interpretation. The registry record does not report confidence intervals for the listed safety counts. With small cohorts, estimates based on only a few participants are intrinsically imprecise, and a change in the event status of one participant can substantially alter the count relative to the cohort size. This is one reason to avoid treating the observed group values as stable estimates of risk.

Why do the study stages matter?

Phase 1b dose escalation and Phase 2a tumor-specific cohorts have different purposes. The early dose-escalation stage was intended to assess safety and tolerability and identify a dose for later study. The later stage sought preliminary anti-tumor activity in specific disease groups. The regimen and cohort membership are not interchangeable across these stages, and observed outcomes can reflect differences in participants, disease, prior treatment, dose, follow-up, and chance. A group comparison that ignores these differences would not isolate a treatment effect.

General statistical explanation: random allocation helps balance known and unknown participant characteristics across groups on average. This study is listed as non-randomized, and it has no control group described in the registry. Thus, the arms should be read as separate cohorts, not as randomized treatment groups. Even a numerical difference between two cohorts would not demonstrate that one regimen or dose produced that difference. A valid comparative effect estimate would require a suitable design and analysis that address the relevant sources of bias and uncertainty; the record does not report such a comparative analysis.

What does sequential enrollment imply?

The registry identifies the model as sequential and describes dose escalation before later cohorts. In general, sequential dose-escalation designs collect safety information in an ordered process to inform decisions about subsequent dosing. The exact decision rules, dose-escalation algorithm, stopping boundaries, or any interim analysis procedures are not reported in the registry record. They should not be inferred from the fact that the study was sequential or from the dose levels listed for the outcome groups.

How should event definitions and time windows be read?

The TEAE definition begins with treatment exposure and includes events that begin or worsen after the first day of treatment. The record specifies a post-treatment window, with a longer window for serious adverse events than for TEAEs. These operational definitions determine which events can contribute to the outcome. They do not establish causality: treatment-emergent means the event occurred in the defined temporal relationship to treatment, whereas treatment-related is a separate attribution category. The registry outcome title distinguishes treatment-emergent and trial treatment-related events. The group figures do not provide a full numerical breakdown of each of those categories in the record.

What can be learned from the listed counts?

Counts can describe the observed safety experience within each cohort. They can also identify event categories warranting attention in further reporting. However, they do not adjust for duration of exposure or differences in observation time. A participant followed longer may have more opportunity for an event to be recorded than a participant followed for less time. The registry lists the primary outcome timeframe as up to 2 years and 3 months, but individual follow-up durations are not reported in the registry record. No exposure-adjusted event rates can be inferred from participant counts alone.

General statistical explanation: over-dispersion is relevant when event counts vary more than a simple probability model would predict, often because participants have different underlying risks or repeated events are correlated. The primary outcome is a participant count rather than a recurrent-event count, and the registry does not report a model that accounts for over-dispersion. It would therefore be inappropriate to claim that a particular model was used or that the posted values have been adjusted for variation in exposure or risk.

What do the planning illustrations mean?

The planning illustrations use assumptions stated for those calculations: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are illustrations based on an observed effect, not the trial's own design justification or observed power. The registry record does not report the trial's sample-size justification, and the planning assumptions should not be mistaken for the design or analysis actually used in this study. Any sample-size figure is a planning aid, not evidence that the trial had a particular probability of detecting an effect.

General statistical explanation: a planning calculation estimates the sample size needed under specified assumptions about an effect, variability, significance level, and allocation. Its result depends on those assumptions. If the effect used for planning comes from a small or selected cohort, it may be uncertain; planning for a fraction of that effect represents a scenario rather than a new observed finding. Without a randomized comparison and a prespecified design, such illustrations do not establish the adequacy or success of this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, spanning safety, response, disease control, time-to-event outcomes, overall survival, anti-drug antibodies, and biomarker-cohort measures. Testing or interpreting many outcomes can increase the chance of finding an apparently notable result by chance if multiple inferential tests are performed. General statistical explanation: multiplicity procedures can control that risk, for example by adjusting significance thresholds or specifying a hierarchy of outcomes. The registry record does not report a multiplicity strategy, a hierarchy for interpreting outcomes, or a statistical analysis plan. It also lists no analyses, so there are no reported inferential results from which to assess multiplicity adjustment.

The primary endpoint analysis population is described as the Safety Analysis Set: participants who received at least one dose, even partially, of one or both trial medications. Only Phase 1b participants were analyzed for this primary outcome. This definition is important because the outcome is about treatment-emergent safety events among exposed participants, not all people enrolled. The registry record does not report detailed exclusions, the handling of participants who discontinued early, or how missing safety observations were handled.

Missing data can affect both counts and time-to-event outcomes. General statistical explanation: if outcome status is unknown for some participants, treating them as event-free, excluding them, or using an imputation method can yield different estimates. The appropriate approach depends on why data are missing and on the outcome. The registry record does not report missing-data methods, completeness by outcome, or censoring rules for secondary time-to-event measures.

The Phase 2a efficacy objective and the secondary outcomes should therefore be considered distinct from the reported Phase 1b safety outcome. No statistical analysis plan, interim analysis details, or adjustment for multiple outcomes is reported in the registry record. These omissions limit what can be concluded about prespecification and the inferential status of any reported findings.

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: malignant neoplasm progression (41.2%), gastritis (33.3%), immune-mediated gastritis (33.3%), dyspnoea (33.3%), cough (33.3%).

The serious adverse event figures are participant counts within the listed cohorts. For example, the Phase 1b dose-level entries give the number with serious adverse events and the number at risk in each group. These are not rates adjusted for exposure time, and they are not comparisons against a control group. The study is non-randomized, and the cohorts differ in stage and participant characteristics.

The registry defines serious adverse events by outcomes such as death, a life-threatening event, hospitalization or prolonged hospitalization, significant incapacity, congenital anomaly or birth defect, and important medical events judged to require intervention. A serious adverse event is not necessarily caused by the study drugs. The term treatment-related refers to a separate attribution; the listed serious-event counts alone do not reveal whether events were judged related.

Deaths are listed by group, but those counts should not be read as treatment-related deaths. The serious-event terms and percentages are also descriptive entries; the record does not provide enough context to interpret each percentage as a group-specific risk. Because participant counts can include only people observed within the defined follow-up, the counts should be read alongside the study's event definitions and the absence of individual follow-up detail.

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

The registry record establishes that the study evaluated NT-I7 with pembrolizumab in a non-randomized, open-label sequence of dose-escalation and disease-specific cohorts. It also reports participant counts for serious and other adverse events in the listed groups. These data describe observed safety events among the participants included in those groups; they do not by themselves establish the cause of an event or compare the combination with an untreated or alternative-treatment group.

The stated purpose of Phase 1b was safety, tolerability, and dose selection, while the stated Phase 2a purpose was preliminary assessment of anti-tumor activity. Those aims do not substitute for outcome estimates. The registry record does not report numerical efficacy results, confidence intervals, or hypothesis tests for response, disease control, progression-free survival, or overall survival. It is therefore not possible from the listed safety counts to determine the size or precision of any anti-tumor effect.

Likewise, the record's serious-event counts should not be treated as evidence that the combination is safe or unsafe overall. That judgment would require a fuller account of adverse-event types, severity, timing, exposure, treatment attribution, missing observations, and a suitable context for comparison. A participant count can be informative without being a causal estimate.

General statistical explanation: a result is most informative when its estimate, uncertainty, analysis population, outcome definition, and study design are considered together. When a study has no randomized comparator, observed cohort outcomes are descriptive and are vulnerable to differences between cohorts. The planning illustrations are also hypothetical scenarios based on stated assumptions, not estimates of observed power and not proof that the trial was designed to detect a particular effect.

The defensible interpretation is consequently narrow: the registry reports safety counts across the study cohorts and records the intended objectives and outcome measures. The record does not report enough statistical detail to support an efficacy conclusion, a treatment-effect estimate, or a precise comparative safety conclusion.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a study objective and a reported result. The registry describes a dose-escalation purpose centered on safety and dose selection, followed by Phase 2a cohorts intended to explore preliminary activity in several tumor types. The available numerical outcome data in the record concern participant-level adverse-event counts. Without numerical efficacy estimates, the stated anti-tumor objective cannot be interpreted as a demonstrated treatment effect.

It also shows why study design must guide statistical interpretation. A non-randomized, sequential set of cohorts can describe safety experience and support development decisions, but the cohorts are not interchangeable controls. Differences in their counts may reflect differences in tumor type, prior checkpoint inhibitor exposure, dose, follow-up, or other participant characteristics. The counts alone cannot separate those explanations.

Another statistical point is the importance of defining the analysis population and endpoint. The primary outcome applies to the Phase 1b Safety Analysis Set, not every person associated with the full study. Its event definitions and follow-up windows determine which adverse events count. Participant counts also differ conceptually from event counts and from exposure-adjusted rates.

Finally, the record lists many outcome measures but does not describe a statistical analysis plan, missing-data approach, multiplicity strategy, or interim analyses. These omissions matter when assessing how outcomes were selected and how uncertainty should be interpreted. The trial therefore offers a useful example of how registry-level descriptions can support a careful account of design and observed safety counts while leaving major questions about efficacy estimation and inferential analysis unresolved.

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 safety results are reported for non-randomized cohorts rather than a randomized comparison. The cohort labels reflect different study stages and tumor or treatment-history groups, so the numbers should not be ranked as if they represented equivalent populations assigned to different interventions. There is no control group described in the registry record.

The primary endpoint is restricted to Phase 1b participants in the Safety Analysis Set. The record does not provide a complete numerical breakdown of every primary-outcome category, including treatment-related TEAEs and treatment-related SAEs, by group. Individual event timing, duration, severity grading, exposure time, and follow-up completeness are not reported in the record. These details would be needed for a fuller assessment of safety patterns.

The study includes several tumor cohorts and secondary outcomes, but efficacy estimates and their uncertainty are not reported in the registry record. The record also does not report the statistical analysis plan, sample-size justification, interim-analysis procedures, missing-data methods, censoring rules, or multiplicity strategy. The listed planning assumptions do not fill those gaps: they are planning illustrations based on observed effects, not the trial's design rationale or observed power.

Finally, the listed death counts and serious-event terms do not by themselves establish treatment causality. The record's temporal definition of treatment-emergent events is distinct from a judgment that an event was treatment-related. Accordingly, these limitations constrain both causal interpretation and the precision with which the overall safety or efficacy experience can be characterized.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors — NCT04332653.
• Registry record last updated 2026-03-09; status last verified 2026-02.
• Results first posted 2026-02-09.
• 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

The registry describes a completed, open-label, non-randomized Phase 1b/2a study of NT-I7 with pembrolizumab in advanced solid tumors. The design was sequential, with Phase 1b dose escalation followed by Phase 2a tumor-specific cohorts and a biomarker cohort. Registry enrollment is 215.

The primary outcome counts Phase 1b participants with treatment-emergent and serious adverse events, including treatment-related categories. The registry reports serious and other adverse-event counts across Phase 1b and Phase 2a groups, as well as listed serious-event terms. The primary analysis population is the Safety Analysis Set, defined by receipt of at least one dose of one or both trial medications.

The registry lists 11 outcome measures but no analyses. Efficacy estimates, a statistical analysis plan, multiplicity methods, and missing-data procedures are not reported in the registry record. The posted counts support descriptive safety interpretation, not a randomized comparison or an efficacy conclusion.