Safety and Tolerability Evaluation of Sintilimab in Combination With Radiation in Stage IV NSCLC Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Evaluation of Sintilimab in Combination With Radiation in Stage IV NSCLC Patients (NCT03812549), a na phase 1 study. The primary outcome is Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT.

2. Clinical Question

The clinical focus is therefore on safety and tolerability in the context of the combined regimen, rather than on a treatment effect compared with a control. The registry also lists progression-free survival, objective response rate, and overall survival as secondary outcomes. Their definitions, estimates, and analyses are not reported in the registry record. The title describes a multi-center study, while the brief summary says all participants would take part at West China Hospital, Sichuan University; the registry record does not clarify this difference.

3. Trial Design

This is a phase I, single-group study listed as completed, with a recorded enrollment of 29. Its stated purpose is to investigate safety and tolerability when sintilimab is combined with concurrent SBRT and LDRT in people with stage IV NSCLC. The official title further identifies treatment-naive, PD-L1-positive disease. The record names Sichuan University as sponsor.

The study is described as a dose-escalation cohort with three dose-level groups in the posted adverse-event results. The registry gives the Dose Level 1 regimen as SBRT at 30 Gy/3f, LDRT at 2 Gy in 1 fraction, and anti-PD-1 inhibitor 200mg. The description for Dose Level 2 begins with SBRT at 30 Gy/3f and LDRT at 4 Gy, but is cut off before the full regimen is stated. Full regimen details for Dose Level 3 are not reported in the registry record. It is therefore not possible to reconstruct all dose-level schedules from the record.

Allocation is listed as not applicable, masking as none, and the model as single group. These details mean that the dose-level cohorts should not be read as randomized treatment arms or as a control comparison. Cohort sizes in the adverse-event record are 6 for Dose Level 1, 17 for Dose Level 2, and 6 for Dose Level 3. Because the design is not randomized, differences between these groups cannot by themselves identify the effect of changing dose or distinguish that effect from differences in who entered each cohort.

The registry records a start date of 2019-01-18 and a primary completion date of 2022-01-31. The record lists safety and tolerability as the primary focus and names progression-free survival, objective response rate, and overall survival as secondary outcomes. A detailed protocol, dose-escalation rules, eligibility criteria, and a 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.

Dose Level 1: 2Gy in 1 Fraction

Dose Level 2: 4Gy in 2 Fractions

Dose Level 3: 10Gy in 5 Fractions

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 Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT, measured over from randomization through 30 days after last dosing, up to 24 months.

The primary endpoint is the number of participants with adverse events and/or dose-limiting toxicities while receiving sintilimab with SBRT and LDRT. The unit is participants, so the intended summary concerns how many people experienced an event, rather than the total number of separate events. The registry states that adverse events and dose-limiting toxicity are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

A participant-count endpoint is relevant in an early-phase safety study because it describes how many people experienced toxicity during the recorded observation period. In general, event grading provides a structured way to classify severity, while dose-limiting toxicity can be used in dose-escalation research to assess tolerability. The registry does not give a separate operational definition of dose-limiting toxicity, nor does it state how adverse events and dose-limiting toxicities are combined when both are considered in the primary endpoint.

The recorded timeframe is “from randomization through 30 days after last dosing, up to 24 months.” The reference to randomization is not explained in a study listed as single group with allocation not applicable. The registry record also does not report a complete primary-endpoint result by dose level. The adverse-event summaries include serious and other event counts, but those counts should not be treated as a complete report of the combined primary endpoint or of dose-limiting toxicity unless the registry explicitly identifies them that way.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The primary outcome is expressed as a count of participants with adverse events and/or dose-limiting toxicities. A participant-based count is different from an event count: one person can experience more than one event, while a participant count records whether the person met the specified outcome. The registry does not explain the exact rule for combining adverse events and dose-limiting toxicities, so it is not possible to determine from the record whether the primary result would count any qualifying event, a particular event grade, or another prespecified criterion.

Why is grading relevant? The record names CTCAE version 5.0 as the grading system. In general, standardized grading supports consistent classification of adverse-event severity. It does not, by itself, establish that a treatment caused an event. Causality assessment, event onset and duration, and the way recurrent events are handled require additional details. These details are not reported in the registry record.

How should the cohort counts be read? The safety data are separated by Dose Level 1, Dose Level 2, and Dose Level 3. Each group has a recorded number at risk and counts for serious and other adverse events. These are descriptive summaries. General statistical principle: a count is easier to interpret when considered alongside its denominator, but small cohorts can still leave substantial uncertainty about the event frequency in a broader population. A percentage or count observed in a cohort is not a guarantee of the corresponding frequency elsewhere. No confidence intervals for these safety summaries are reported in the registry record.

Why does the design matter? The study is listed as single group, with allocation not applicable and masking none. There is no randomized control group. General statistical principle: random assignment can make treatment groups more comparable, on average, for measured and unmeasured factors. Without that design feature, a difference between dose-level groups may reflect cohort composition, timing, or other factors rather than dose. The record also does not describe a formal comparison among dose levels. The adverse-event counts should therefore be interpreted as group descriptions, not as estimates of a comparative treatment effect.

What can a confidence interval add? In general, a confidence interval communicates the uncertainty around an estimate under a specified statistical model. It does not mean that the true value has a particular probability of lying within an already calculated interval, and it does not resolve design limitations such as lack of a control group. No interval estimates are reported for the posted safety outcomes. Without participant-level data, it is not appropriate to derive intervals from the registry summaries for this explanatory account.

What is over-dispersion? General explanation: for some outcomes, observed variability can be greater than a statistical model expects. This is called over-dispersion and can make standard errors too small if ignored. It is particularly relevant to count outcomes when counts vary more widely than a simple model allows. The primary endpoint is a participant count, and the registry does not report a model for that endpoint or evidence that over-dispersion was assessed. This concept should not be mistaken for a finding about this study.

What do the planning assumptions mean? The registry describes planning illustrations based on an observed effect, with 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 outcomes, the illustration is defined in terms of total events; for other outcomes, it is defined in terms of participants per arm. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. The illustrations do not make this single-group trial a two-arm randomized comparison, and their numerical outputs are not reported in the registry record.

What analyses are reported? The record lists 0 analyses. It does not report a statistical analysis plan, model specifications, adjustment methods, hypothesis tests, or uncertainty estimates. The registry also does not state whether dose-level comparisons were planned, whether outcome assessors were blinded, or how missing observations would be handled. As a result, interpretation should remain at the level of the reported descriptive counts and listed event terms.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: progression-free survival, objective response rate, and overall survival. It does not report results or analyses for these outcomes, and it does not describe a testing hierarchy, a primary-secondary testing sequence, or any adjustment for multiple comparisons. General statistical principle: when several outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiple testing. No conclusion about how that issue was handled can be drawn from the registry record.

Missing-data methods are not reported in the registry record. It does not state how participants who stop treatment, miss assessments, or have incomplete follow-up were included in outcome summaries. The timeframe for the primary endpoint is recorded as through 30 days after last dosing, up to 24 months, but the record does not explain how observations with shorter follow-up were treated or how follow-up completeness was assessed. The reference to randomization in that timeframe is not reconciled with the single-group design.

The analysis populations are also not defined. The record does not say whether the safety summaries include all enrolled participants, only participants who received treatment, or another population. Although group counts and numbers at risk are listed, they do not supply a complete account of participant flow or missing assessments. No assumptions about missingness, imputation procedures, sensitivity analyses, or censoring rules are reported.

These omissions matter because a count can depend on who was included and how incomplete follow-up was handled. They do not show that data are missing or that a particular method was used; they mean the registry record does not describe those 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: pneumonitis (16.7%), dermatitis (5.9%), hypertriglyceridemia (5.9%), lipase increased (5.9%), anaphylaxis (5.9%).

The registry separates serious adverse events from other adverse events and reports counts by dose level. In Dose Level 1, the serious-event count is 0 among 6 at risk, and the other-event count is 6 among 6. In Dose Level 2, the corresponding counts are 5 among 17 and 12 among 17. In Dose Level 3, they are 1 among 6 and 6 among 6. Each group lists 0 deaths.

The record's top serious-event terms include pneumonitis at 16.7%, with dermatitis, hypertriglyceridemia, lipase increased, anaphylaxis, and hypoadrenocorticism each listed at 5.9%. The registry does not provide further denominator or event-level details alongside these percentages. The percentages should therefore be quoted as recorded, without assuming how they map to individual dose-level counts.

These summaries do not identify whether events were judged treatment-related, whether people experienced more than one serious event, or how severity grades were distributed. The serious and other adverse-event counts also do not substitute for the primary endpoint result, which includes adverse events and/or dose-limiting toxicities. The registry record does not report a complete result for that combined endpoint. In general, safety counts describe events recorded during observation; they do not by themselves prove causation or precisely predict risk in other groups.

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

The record describes a phase I investigation of sintilimab combined with SBRT and LDRT, with safety and tolerability as its primary focus. It records adverse events by dose-level group and lists several serious adverse-event terms. Those data are useful as descriptive information about the participants included in the registry results. They do not, on their own, establish the cause of an event or determine how the regimen compares with another treatment.

The single-group design is central to interpretation. There is no randomized control group, and the dose-level groups are not a like-for-like control comparison. Differences in their recorded counts cannot be attributed to dose from these summaries alone. The record also does not provide inferential analyses, confidence intervals, or a complete primary-endpoint result. The precision of the observed safety counts is therefore not quantified in the registry record.

The listed secondary outcomes—progression-free survival, objective response rate, and overall survival—do not have reported results or analyses in the record. The available information cannot establish an efficacy benefit, compare clinical outcomes with another regimen, or support a conclusion about how outcomes would differ in a broader patient population.

General statistical principle: an observed result describes the people and follow-up represented in the analysis, while generalization depends on study design, measurement, and completeness of data. Here, the analysis populations, missing-data methods, and detailed follow-up procedures are not reported in the registry record. The appropriate interpretation is consequently limited to the descriptive safety summaries and the study's stated aims. The record does not support a definitive conclusion about overall safety, comparative effects, or outcomes beyond the enrolled cohorts.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of an early-phase, single-group safety study. Such designs can organize initial observation of tolerability across dose levels, while their results remain descriptive in the absence of a control group. The record identifies the main measurement as a participant count for adverse events and/or dose-limiting toxicities, and it specifies CTCAE version 5.0 as the grading framework.

The design also illustrates why study structure should be considered before comparing group summaries. The three dose-level cohorts have different recorded sizes, and the record does not describe random assignment or a formal comparative analysis. General statistical principle: counts may be useful for describing what was observed, but they do not isolate the effect of a dose when groups are not made comparable by design or analysis. This is especially important when the registry provides no uncertainty estimates.

The record also makes the distinction between outcome listing and outcome analysis visible. Progression-free survival, objective response rate, and overall survival are named as secondary outcomes, but results and analyses are not reported. Naming an outcome does not itself provide evidence about its value or establish how it was measured.

Finally, the registry's planning assumptions describe a two-arm illustration, whereas the study itself is listed as single group. This makes it important to separate planning scenarios from the study design actually recorded. Planning calculations are not observed power and cannot replace reported analyses. The record is therefore most useful for understanding the stated safety question, the descriptive event counts, and the limits imposed by missing analysis details.

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 main design limitation is the absence of a separate control group. Allocation is listed as not applicable, the study model is single group, and masking is listed as none. Dose-level groups are not randomized comparisons, so differences in their adverse-event counts cannot establish a dose effect or a relative effect against another treatment.

The registry record gives an enrollment of 29 and group sizes of 6, 17, and 6 in the posted adverse-event summaries. These cohort sizes provide limited descriptive information, and the record reports no confidence intervals or other uncertainty estimates. The absence of such estimates prevents a direct assessment of precision from the posted results.

Important methods are not reported in the registry record, including the complete protocol, detailed dose-escalation rules, a full definition of dose-limiting toxicity, analysis populations, missing-data procedures, and the statistical analysis plan. The primary endpoint timeframe refers to randomization even though the study is listed as single group; this wording is not explained. The registry lists secondary outcomes but does not report their results or analyses.

The dose description is incomplete for later dose levels. The official title calls the study multi-center, while the brief summary says all participants would take part at West China Hospital, Sichuan University; the record does not clarify this difference. The serious-event term percentages are listed without further denominator detail. These limitations constrain interpretation of the posted data and make it inappropriate to infer unreported methods or outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability Evaluation of Sintilimab in Combination With Radiation in Stage IV NSCLC Patients — NCT03812549.
• Registry record last updated 2025-03-04; status last verified 2025-02.
• Results first posted 2025-03-04.
• 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 record describes a completed phase I, single-group study of sintilimab with SBRT and LDRT in stage IV NSCLC, with recorded enrollment of 29. The stated primary focus is the number of participants with adverse events and/or dose-limiting toxicities, graded according to CTCAE version 5.0. The record lists adverse-event counts for three dose-level groups and names progression-free survival, objective response rate, and overall survival as secondary outcomes.

No randomized comparator is described, and the posted adverse-event counts are descriptive. The registry lists 0 analyses and does not report inferential results, confidence intervals, a complete primary-endpoint result, or analyses for the secondary outcomes. Important details concerning analysis populations, missing data, and the statistical plan are not reported in the registry record. Interpretation should therefore remain limited to the stated study design and recorded safety summaries.