A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors (NCT02869295), a na phase 1, phase 2 study. The primary outcome is Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a Phase 1/2, multicenter study of NKTR-214 in subjects with locally advanced or metastatic solid tumors. The brief summary describes it as a first-in-human, open-label, sequential dose-escalation and expansion Phase 1 study in adults. The record lists both Phase 1 and Phase 2, but it does not provide enough detail to reconstruct how the stages were implemented or how participants entered any expansion stage.

The study was open-label, meaning masking was not used. Its model is listed as sequential, and allocation is listed as NA. It is therefore not a randomized comparison: the listed dose groups are not like-for-like control arms. Differences in their posted counts cannot establish that dose or schedule caused differences in outcomes.

The registry lists an enrollment of 28 and five NKTR-214 dose groups: 0.003 mg/kg q21d, 0.006 mg/kg q21d, 0.006 mg/kg q14d, 0.009 mg/kg q21d, and 0.012 mg/kg q21d. The safety records give the number at risk within each group as 4, 11, 6, 6, and 1, respectively. Enrollment and group-level safety counts are distinct record entries; the registry does not explain any differences between them.

The study is marked completed. Its start is listed as 2015-12, and primary completion as 2018-10-31. The registry describes a primary safety outcome based on drug-related adverse events, with a timeframe through 30 days after the last dose, approximately 533 days. Detailed information about the protocol, dose-escalation decision rules, expansion cohorts, or the statistical plan is 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 Sponsor discontinued enrollment in order to allow the clinical development program for NKTR-214 to continue with other studies in which NKTR-214 was administered in combination with checkpoint inhibitors, based on biomarker analysis, which showed infiltration of immune cells within tumor tissue.

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 Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs), measured over 30 days after last dose, approximately 533 days.

The primary outcome is titled “Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs).” The measure is recorded as a number of events, and the description says it quantifies the number and types of adverse events associated with NKTR-214. The assessment timeframe is 30 days after the last dose, approximately 533 days.

Safety outcomes are used in early-phase studies to describe adverse events observed during treatment and follow-up. As a general statistical point, counts can convey the burden of recorded events, while the types of events add clinical context. A count is not the same as the number of participants affected: one participant may have more than one event. The registry record does not clarify whether the primary count is event-level or participant-level in the posted results.

The endpoint title specifies drug-related adverse events, but the registry record does not provide a primary endpoint result or an analysis relating the adverse-event counts to treatment. The serious and other adverse-event counts are listed by dose group, but their relationship to the defined primary endpoint is not specified. The listed safety counts should therefore be read as descriptive safety information, not as a numerical estimate of a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the study design tell us?

The registry classifies the study as Phase 1 and Phase 2, open-label, and sequential. In general, dose-escalation studies examine a treatment at successive dose levels, while expansion stages can collect further experience in selected groups. The registry summary describes this study as a first-in-human dose-escalation and expansion study, but details of the stage-specific procedures are not reported in the registry record.

Open-label means participants and study personnel were not masked to treatment assignment. Allocation is listed as NA, and there is no randomized control group described. As a general design principle, random allocation can help make groups comparable at baseline; without it, group differences may reflect participant characteristics, timing, exposure, or other factors as well as dose. The posted group counts should therefore be interpreted descriptively rather than as causal dose comparisons.

What does a count outcome represent?

The primary outcome is recorded as a number of adverse events. In general, count outcomes record how many events occur in a defined group or observation period. The number of events may differ from the number of people with an event, because an individual can experience multiple events. The registry record does not explain how the primary count was constructed in the posted results, nor does it provide a primary outcome result.

As a general statistical consideration, count data can be more variable than a simple model assumes, particularly when a few participants contribute multiple events. Over-dispersion describes variability greater than a model's expected level. It can affect uncertainty estimates if a model does not account for it. The registry record does not report a count-data model or any assessment of over-dispersion, so no such method should be attributed to this study.

How should uncertainty and comparisons be understood?

A confidence interval is a range expressing the uncertainty around an estimated quantity under a statistical method. In general, a wider interval indicates less precision, while a narrow interval indicates greater precision under the model used. The registry record reports no confidence intervals or comparative estimates for the posted safety figures. Without these, the counts alone do not quantify the precision of a difference between dose groups.

A p-value is a measure calculated under a specified statistical model and null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true. No p-values or hypothesis tests are reported in the registry record. The stated significance level of 0.05 belongs to planning illustrations, not to a reported analysis of this study.

Planning calculations based on an observed effect are hypothetical exercises that estimate what sample size might be needed under stated assumptions. The stated approach uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. These calculations are not the trial's original design justification, do not describe actual randomized arms, and are not observed power. The registry does not report the protocol's sample-size justification.

What can the safety summaries establish?

The registry lists serious adverse event counts, other adverse event counts, deaths, and percentages for selected serious-event terms by group. Such summaries can describe what was recorded, but they do not by themselves establish cause, comparative risk, or a dose-response relationship. A causal interpretation would require more information about the study design, exposure, timing, event definitions, and analysis. Those details are not reported in the registry record.

The primary safety outcome refers specifically to drug-related adverse events, whereas the group safety entries are presented as serious and other adverse events. The record does not establish that every listed event was considered drug-related or explain how relatedness was judged. These distinctions matter: all adverse events, serious adverse events, and events judged related to treatment are not interchangeable categories.

The record also does not state whether events were analyzed as recurrent counts, whether participants were followed for equal durations, or how missing safety observations were handled. Without those methods, the posted numbers can be described as recorded counts, but cannot be converted into exposure-adjusted rates or used to estimate a model-based treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a hierarchy of outcome tests, or a multiplicity adjustment. Multiplicity arises when many outcomes, groups, or comparisons are tested: as a general statistical principle, more testing can increase the chance of a nominally notable result arising by chance. No inferential results are posted here, so the record does not permit an assessment of how any multiplicity strategy affected conclusions.

The registry lists two outcome measures, but the details of the other measure and its results are not reported in the registry record. The primary outcome is a number of drug-related adverse events. No statistical analysis, effect estimate, confidence interval, or p-value is reported for it. Protocol-specific decisions about outcome selection, analysis, or multiplicity are not reported in the registry record.

Analysis populations are also not described. The record does not say which participants were included in each endpoint analysis, how participants who stopped treatment were handled, or whether any analysis population was defined in advance. Missing-data methods, the amount of missing outcome information, and reasons for missingness are not reported in the registry record.

These omissions limit interpretation of the posted counts. Without population definitions and missing-data details, it is not possible to determine whether the counts represent all enrolled participants, participants who received treatment, or another analysis set. Without a specified analysis plan, no particular inferential method should be assumed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: syncope (100.0%), hypotension (100.0%), cytokine release syndrome (100.0%), pleural effusion (50.0%), abdominal pain (33.3%).

The serious adverse event entries give the number at risk and the number affected in each dose group. For 0.003 mg/kg q21d, 2 of 4 were affected; for 0.006 mg/kg q21d, 5 of 11; for 0.006 mg/kg q14d, 4 of 6; for 0.009 mg/kg q21d, 3 of 6; and for 0.012 mg/kg q21d, 1 of 1. These are group counts, not results of a randomized comparison.

The registry also lists the number affected by other adverse events as 4, 11, 6, 6, and 1, respectively. The death counts are 2, 3, 2, 1, and 0 across the same groups. The record does not say that these deaths were treatment-related or provide their causes, so the counts do not establish attribution.

The registry lists selected serious-event terms with percentages: Syncope, Hypotension, and Cytokine Release Syndrome are each listed as 100.0%; Pleural Effusion as 50.0%; Abdominal Pain as 33.3%; and Constipation as 25.0%. The denominators and calculation details are not reported in the registry record. These percentages should not be interpreted as incidence rates for the full study population.

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

The record documents a completed, open-label, sequential study of NKTR-214, with enrollment listed as 28 and five dose groups represented in the posted safety data. It provides counts for serious and other adverse events, deaths, and selected serious-event terms. Those data give a descriptive account of what was recorded in the groups.

The counts do not show whether the dose groups were comparable, because this was not a randomized comparison. Their sizes differ, and the registry does not report adjusted analyses or uncertainty estimates. Consequently, apparent differences among groups should not be read as evidence that one dose or schedule caused more or fewer events. Nor do the event counts alone establish treatment-relatedness; the primary outcome is specifically framed around drug-related events, while the detailed relatedness procedures are not reported in the registry record.

The death counts do not identify cause or attribution. The record does not provide an efficacy result, a comparative treatment-effect estimate, or statistical tests. It therefore does not establish that NKTR-214 improved outcomes, failed to improve outcomes, or differed from another treatment. Those are not conclusions supported by the posted information.

More generally, a study's recorded outcomes and the strength of an inference are different things. Counts describe observations; estimates with uncertainty and a suitable comparative design are needed to assess differences. A planning illustration based on an observed effect is not a finding from a randomized comparison and is not observed power. The registry record supports a limited descriptive reading of safety reporting, while leaving the causal and comparative questions unresolved.

13. Why This Trial Matters Statistically

This record illustrates an important distinction in clinical biostatistics: descriptive safety counts are not automatically comparative evidence. The study was open-label and sequential, with allocation listed as NA and no like-for-like control group. Although multiple dose groups are listed, their counts cannot be interpreted as if participants had been randomized between otherwise comparable arms.

The endpoint also highlights why careful outcome definitions matter. The primary outcome concerns the number of drug-related adverse events, while the posted group summaries distinguish serious and other adverse events. Without details on event attribution and how the primary count was assembled, those categories should not be treated as equivalent. The registry's selected serious-event percentages also lack reported denominators, limiting their interpretation.

Small, unequal group counts make uncertainty especially important. Counts can describe what was observed, but they do not by themselves show how precisely a difference has been estimated. The record reports no confidence intervals, p-values, or adjusted comparisons. It also does not report the statistical plan or missing-data methods. These gaps prevent readers from reconstructing an inferential analysis from the registry information.

Finally, planning calculations and observed results answer different questions. A hypothetical sample-size illustration based on a specified fraction of an observed effect describes assumptions for a planning exercise; it does not show the study's actual power or establish a treatment effect. This distinction is essential when reading dose-escalation safety data, where the aim and structure differ from a randomized comparative trial.

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 registry summary identifies the study as a first-in-human, open-label, sequential dose-escalation and expansion study, but detailed design information is limited. Dose-escalation rules, expansion procedures, eligibility criteria beyond the broad adult solid-tumor description, and participant flow are not reported in the registry record. These omissions restrict interpretation of how the dose groups were formed and how observations accumulated.

The record lists enrollment as 28, while the group-level safety counts show different numbers at risk. It does not explain the relationship between those entries, nor does it specify whether the risk counts represent all enrolled participants, treated participants, or a particular safety population. Follow-up duration by participant and exposure time by group are not reported, so the event counts cannot be interpreted as exposure-adjusted rates.

The primary outcome is described as drug-related adverse events, but no primary result or analysis is reported. The record does not explain event definitions, relatedness assessment, coding procedures, or whether multiple events per person were counted. The denominators for the listed serious-event percentages are also not reported. Death causes and treatment attribution are absent.

No randomized comparator, inferential analysis, confidence interval, p-value, analysis population, missing-data method, multiplicity approach, or statistical analysis plan is reported in the registry record. These limitations mean the posted information supports descriptive reading only and cannot establish causal safety differences, comparative effectiveness, or the precision of a treatment effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors — NCT02869295.
• Registry record last updated 2021-07-29; status last verified 2021-07.
• Results first posted 2021-07-29.
• 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.

18. Record Summary

NCT02869295 is a completed Phase 1/2, multicenter, open-label, sequential study of NKTR-214 in adults with locally advanced or metastatic solid tumors. The registry describes it as a first-in-human dose-escalation and expansion study. Enrollment is listed as 28; the five safety groups cover dose levels of 0.003 mg/kg q21d, 0.006 mg/kg q21d, 0.006 mg/kg q14d, 0.009 mg/kg q21d, and 0.012 mg/kg q21d.

The primary outcome concerns the number of drug-related adverse events through 30 days after the last dose, approximately 533 days. Posted safety entries include serious and other adverse events, deaths, and selected serious-event terms. The registry record does not report a randomized comparison, a primary outcome result, inferential analyses, or the statistical plan. The group counts are descriptive and do not establish causation or comparative treatment effects.