A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors (NCT02009449), a non-randomized phase 1 study. The primary outcome is Number of Participants With TEAEs and SAEs Observed During the Study of Pegilodecakin.

2. Clinical Question

The study asked whether pegilodecakin could be administered to participants with advanced solid tumors at escalating doses, alone or with other anticancer drugs, while assessing tolerability and safety. Its official title also identifies maximum tolerated dose, preliminary clinical activity, and pharmacokinetics as aims. The primary outcome recorded the number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

The study was first-in-human and open-label, so its design was suited to describing observed safety experience across dose levels and treatment combinations, alongside preliminary clinical activity and pharmacokinetics. The record does not report a randomized efficacy comparison or a prespecified comparative treatment effect. Although overall response rate is listed among the secondary outcomes for Parts A through G, numerical response results are not reported in the registry record. The posted safety counts can describe events recorded in this study, but they cannot by themselves determine which treatment caused an event or establish how the experience compares with an alternative.

3. Trial Design

This was a Phase 1, first-in-human study with open-label treatment and non-randomized allocation. The registry identifies the model as single group, but the study included multiple dose levels and treatment parts. Participants received pegilodecakin alone in Part A, or pegilodecakin with chemotherapy, targeted therapy, or immunotherapy in other parts. The record gives combinations including platinum/taxane, FOLFOX, gemcitabine/nab-paclitaxel, capecitabine, paclitaxel, pazopanib, pembrolizumab, nivolumab, and gemcitabine/carboplatin.

Pegilodecakin was administered subcutaneously once daily. Dose levels differed across parts, and combination schedules also differed according to the accompanying drug. For example, the record describes chemotherapy cycles of different lengths and treatment on specified cycle days. It does not describe a common randomized comparator regimen. Treatment was generally continued until disease progression, death, unacceptable toxicity, or the end of the trial where those stopping conditions are stated; full details for every arm are not available in the registry record.

The registry reports enrollment of 353 and classifies the study as completed. The recorded start date is 2013-11-15 and primary completion date is 2019-02-19. Those dates describe the registry timeline; they do not, on their own, tell how long any individual participant was followed. The primary safety timeframe runs from first dose through 30 days after the last dose, with the outcome timeframe described as up to 63 Months.

The design supports descriptive assessment of safety across dose and combination groups. It does not provide the protection against confounding that random assignment can offer: patients in different parts may differ in treatment, disease context, follow-up, or other factors. The registry record does not report the allocation procedure in enough detail to characterize how participants entered each part, nor does it report a formal sample-size justification or a statistical analysis plan. The findings should therefore be read as experience within the study groups, not as a controlled estimate of relative treatment effects.

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.

Only the first 6 of 23 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of study intervention.

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.

Population: All Participants who received one dose of study intervention(s).

Only the first 6 of 24 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With TEAEs and SAEs Observed During the Study of Pegilodecakin, measured over From first dose of study drug through 30 days after the last dose of study drug (Up to 63 Months).

The primary endpoint counts participants who experienced treatment-emergent adverse events and serious adverse events during the study. The registry defines the safety population as participants who received at least one dose of study intervention. The stated timeframe begins with the first dose and continues through 30 days after the last dose, with the outcome listed as up to 63 Months. These definitions identify the population and observation window for the safety assessment.

A participant count is a straightforward way to describe how many people in each treatment group had at least one event of the specified category. For safety monitoring in an early-phase study, such counts help characterize the observed tolerability experience as doses and combinations are explored. They do not convey all details of the event experience: the endpoint does not, as stated, summarize the number of events per person, their duration, severity distribution, or timing. Those details require separate outcome definitions and results.

TEAEs are events arising in the treatment-emergent observation period; their appearance during that period does not by itself establish that the study drug caused them. SAEs are a seriousness category, not a judgment that an event was caused by treatment. The record describes the endpoint as the number of participants with TEAEs and SAEs, but does not report a causal-attribution method in the available information.

This endpoint is appropriate for describing safety observations, but it is not an efficacy endpoint and does not compare pegilodecakin with a control treatment. The registry lists overall response rate among secondary outcomes in several study parts, but numerical response results and details of their analysis are not reported in the registry record. The primary safety count therefore cannot answer whether treatment improved cancer outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the study design and the type of endpoint. This record describes a non-randomized, open-label Phase 1 study with a single-group model. Its primary outcome is a count of participants with adverse events, a binary participant-level outcome for each event category: a participant either is or is not counted as having an event in that category under the outcome definition. The posted group counts are descriptive summaries rather than results from a randomized treatment contrast.

Why does randomization matter?

In a randomized comparison, assignment by chance can help balance measured and unmeasured participant characteristics across treatment groups. That balance supports a more credible estimate of the effect of treatment assignment. Here, allocation was non-randomized, and the arms include different pegilodecakin doses and co-treatments. Groups can therefore differ for reasons other than the treatment component under consideration. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjusted comparative analysis or enough information to assess such an approach.

What does a participant count tell the reader?

A count states how many participants met an outcome definition in a group. The associated at-risk count indicates the group denominator recorded for that outcome. Counts are intuitive, but alone they do not show uncertainty, account for follow-up duration, or distinguish one event from repeated events in the same person. A percentage can help describe a group proportion, but interpretation still depends on the denominator definition, observation time, and completeness of event ascertainment. No new rate or comparative estimate should be inferred from the count alone.

In general, a confidence interval describes a range of values compatible with the data under a specified statistical model and conveys uncertainty about an estimate. It does not guarantee that the true value falls inside the interval, and it does not remedy a biased design. Confidence intervals for the primary outcome are not reported in the registry record. Likewise, the available record does not report a hypothesis test or a prespecified margin for a clinically meaningful difference.

How should the different groups be treated?

Each dose or combination group is a separate descriptive context. A comparison across groups could be confounded by differences in participant mix, disease type, treatment schedule, or follow-up. The registry lists broad advanced solid tumor conditions and multiple treatment combinations, so a pooled summary could also conceal meaningful heterogeneity. A valid pooled estimate would require a defined estimand and a justified analysis strategy; these are not reported in the registry record. The group counts should therefore be read separately rather than combined into a total.

What does over-dispersion mean in general?

For count outcomes, a simple statistical model may assume that variability follows a particular pattern. Over-dispersion means the observed variability is greater than that model expects. If ignored, uncertainty can be understated and tests can appear more decisive than warranted. This concept is general; the primary endpoint is a count of participants with an event, not a count of repeated events, and the registry record does not report a model for over-dispersion or an event-rate analysis.

How do the planning illustrations differ from trial results?

Any sample-size planning illustration accompanying these results is not an observed property of this trial and is not observed power. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are assumptions for a hypothetical planning exercise, not the registry's own design justification. The trial itself was not a randomized, equal-allocation comparison, so those assumptions do not describe its treatment groups. The registry record does not report its sample-size justification.

General power calculations estimate how often a planned analysis would reject a null hypothesis under specified assumptions if a particular effect were true. They do not establish that an observed effect is real, and retrospective planning illustrations cannot substitute for a prespecified analysis. No power or sample-size rationale is reported in the registry record. For this study, the main statistical task is to describe safety findings in their design context, while avoiding causal or comparative claims that the study structure cannot support.

What cannot be reconstructed from the registry record?

Details needed to reproduce a formal analysis—including outcome-level missingness, censoring rules for the safety counts, adjudication procedures, model specifications, and multiplicity control—are not reported in the registry record. Without those details, the analysis should not be reverse-engineered from the group counts. The numerical summaries remain interpretable as posted observations, subject to the definitions and limitations stated in the record.

10. Multiplicity, Missing Data and Analysis Populations

The study includes multiple dose levels, several combination regimens, and multiple outcome measures. Looking across many groups and outcomes creates opportunities to notice apparently large or small findings by chance. In general, multiplicity procedures can control the chance of false-positive conclusions across a defined family of tests. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified family of comparisons. Since no comparative hypothesis tests are reported in the available information, statistical significance should not be inferred from the adverse-event counts.

The registry lists 13 outcome measures and names anti-pegilodecakin antibody formation and overall response rate for Parts A through G among the secondary outcomes. It does not report numerical results for those efficacy outcomes in the information. The analysis plan for secondary outcomes, including any handling of multiple comparisons, is not reported in the registry record.

Missing-data methods and the amount of missing outcome information are not reported in the registry record. The primary safety population is defined as participants who received at least one dose of study intervention, but that does not specify how participants with incomplete follow-up, missing event status, or early discontinuation were handled analytically. Nor does the record state whether missing outcome information was assumed to be absent, excluded, or addressed by another method. These possibilities should not be guessed.

The registry does not describe the analysis population for response outcomes or the rules used to assess response. It also does not report a detailed statistical analysis plan, interim analyses, or the prespecification status of the reported summaries. Therefore, the posted counts can be described according to their stated safety definitions, but broader claims about missingness, confirmatory testing, or a planned analysis cannot be verified from the registry record.

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: alanine aminotransferase increased (100.0%), aspartate aminotransferase increased (100.0%), small intestinal obstruction (50.0%), anaemia (40.0%), ascites (33.3%).

The safety results give group-specific counts of participants at risk, participants with serious adverse events, participants with other adverse events, and deaths. Read each count within its own treatment group and alongside that group's at-risk count. For example, Part A at 1.6/2 mg lists 60 participants with a serious adverse event among 117 at risk and 116 participants with other adverse events among 117 at risk; the group also lists 105 deaths. These are registry-recorded observations, not evidence that treatment caused an event or death.

Groups differ in size and regimen, so counts should not be compared as if the groups were randomized arms of a controlled study. The death counts are not identified as treatment-related in the information available, and their relationship to the adverse-event categories is not specified. The registry also does not provide event timing, participant-level overlap between categories, or group-specific follow-up distributions.

Seriousness and severity are not interchangeable concepts. A serious adverse event is classified by seriousness criteria; the record's count does not imply that every event had the same intensity. The listed serious-event terms include alanine aminotransferase increased and aspartate aminotransferase increased at 100.0% each. The denominator for those term percentages is not reported in the registry record, so they should not be interpreted as percentages of all enrolled participants.

Counts describe the observed safety experience in this study. They do not estimate comparative risk against an untreated or alternative-treatment group.

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

The result establishes that adverse events, including serious adverse events, were recorded among participants who received study intervention and were followed under the registry's safety timeframe. It provides group-specific counts across pegilodecakin doses and combination regimens. Those observations are relevant to describing the safety experience of this first-in-human study, and the counts should be interpreted with their group denominators and treatment context.

The result does not establish that pegilodecakin caused each event. Events arising during treatment can reflect the underlying cancer, concomitant therapies, other health factors, or the study drug. A registry count alone cannot separate these explanations. The record also does not support a causal comparison between dose groups or between combination regimens, because participants were not randomized and the groups did not receive a common treatment apart from pegilodecakin.

The result does not establish efficacy. Although preliminary clinical activity was an aim and ORR appears among secondary outcomes, numerical ORR results are not reported in the registry record. There is no randomized comparator in the design information, and no comparative efficacy estimate is reported. An absence of numerical efficacy results in this record should not be interpreted as evidence that there was or was not a clinical response.

The results also do not supply a complete account of the distribution of harm. The primary endpoint counts participants, rather than describing all event episodes, duration, time to onset, or severity. The available record does not report all participant-level details or follow-up patterns needed to derive event rates. Percentages attached to selected serious-event terms lack a reported denominator in the record and must be interpreted narrowly.

Statistically, the most defensible conclusion is descriptive: the registry records safety events in groups treated with pegilodecakin alone or with other agents. The study design and reporting do not justify claims that one dose or combination is safer, that pegilodecakin changes risk relative to another treatment, or that the observed event patterns predict those in a broader population. Those questions require suitable comparative evidence and additional detail beyond these registry summaries.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the role and limits of early-phase, non-randomized evidence. A first-in-human dose-escalation study can characterize the types of adverse events observed while exploring different doses and combinations. Descriptive safety counts are useful in that setting, particularly when the treatment regimens and populations are heterogeneous. Their value depends on preserving the group context rather than collapsing observations into an unsupported comparison.

The record also shows why an endpoint definition is essential. A count of participants with TEAEs or SAEs answers a different question from a count of event episodes, a severity summary, a time-to-event measure, or a rate adjusted for follow-up. The primary endpoint specifies a treated safety population and a post-treatment observation window. Those details constrain what can be inferred from the outcome and help prevent an event count from being mistaken for a complete safety profile.

Another statistical lesson is that a large overall enrollment does not make every dose or combination estimate precise. The group sizes vary, and several groups contain relatively few participants. Uncertainty and potential instability must be considered at the group level. Without reported confidence intervals or a comparative model, the posted counts do not quantify precision beyond the observed denominators.

Finally, the trial demonstrates the distinction between exploratory aims and confirmatory evidence. Preliminary clinical activity was an objective, and ORR was listed as a secondary outcome in several parts, but numerical response results are not reported in the registry record. The open-label, non-randomized structure is suited to describing treatment experience, not to establishing a causal efficacy effect. Sound interpretation therefore recognizes the contribution of descriptive safety observations while keeping causal, comparative, and efficacy claims within the limits of the design and reporting.

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 broad advanced-solid-tumor population includes multiple cancer types, and the treatment groups differ in dose and co-treatment. This clinical and regimen heterogeneity makes a single summary difficult to apply to any one disease or combination. The registry record does not provide enough subgroup detail to assess whether observed safety patterns vary by cancer type or other participant characteristics.

Non-randomized allocation and the absence of a control group limit causal interpretation. Differences between groups may reflect participant selection, disease context, co-treatment, dose, follow-up, or other factors. The record does not report adjusted comparisons that could address measured differences, and adjustment would not necessarily resolve unmeasured confounding.

Group sizes vary, including small dose and combination groups. Counts in small groups can be sensitive to individual cases, and the registry information does not provide confidence intervals for the primary safety counts. The record also does not report group-specific follow-up distributions, exposure time, or a detailed account of missing safety observations. Counts therefore cannot be converted into exposure-adjusted rates from the information available.

Interpretation of selected serious-event term percentages is limited because their denominators are not reported in the registry record. The relationship between the listed deaths and adverse-event categories, event attribution, and the details of event severity are also not reported. Numerical results for secondary response outcomes are not reported in the registry record, restricting assessment of the preliminary activity objective.

Finally, the registry record does not report the statistical analysis plan, sample-size justification, missing-data procedures, multiplicity approach, or interim analyses. These omissions limit assessment of prespecification and analytic choices. The limitations do not erase the descriptive safety observations, but they define the scope of conclusions that can reasonably be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors — NCT02009449.
• Registry record last updated 2026-07-09; status last verified 2026-06.
• Results first posted 2026-07-09.
• 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

This completed Phase 1 study evaluated pegilodecakin in participants with advanced solid tumors, as monotherapy and in combination regimens. It was open-label, non-randomized, and classified as a single-group model. The registry reports enrollment of 353, a start date of 2013-11-15, and a primary completion date of 2019-02-19.

The primary endpoint counted participants with TEAEs and SAEs among those who received at least one dose, from first dose through 30 days after the last dose; the timeframe is listed as up to 63 Months. Posted adverse-event counts are descriptive and are not randomized comparisons or proof of treatment causation. The registry lists ORR among secondary outcomes, but numerical response results are not reported in the registry record. Details of missing-data handling, multiplicity, and the statistical analysis plan are also not reported in the registry record.