Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC (NCT04476797), a randomized phase 1, phase 2 study. The primary outcome is Percent of Patients With a Complete Response or Partial In-field Tumor Response Based on the RECIST 1.1 Criteria Through 6 Months Following SBRT..

2. Clinical Question

This question combines treatment assignment with an imaging-based tumor-response assessment. The registry describes chest, abdomen, and pelvis CT at baseline, followed by reassessments using the same imaging modality at stated follow-up times. Each reassessment was compared with the previous best response using RECIST 1.1 criteria.

The clinical question is not answered by the record’s design description alone. No primary-outcome counts by group, treatment-effect estimate, confidence interval, or statistical test are reported in the registry record. The record also does not give the individual response-category results or explain how the multiple listed follow-up times relate to the endpoint title’s focus on response through 6 months. Consequently, the planned comparison can be described, but its observed efficacy result cannot be reconstructed from the record.

3. Trial Design

GRECO-1 is listed as a Phase I/II, randomized, placebo-controlled study of GC4711 and SBRT for centrally located or large, node-negative NSCLC. The registered design is parallel-group, with triple masking recorded. The trial status is terminated, and the recorded enrollment is 47.

The brief study description distinguishes an open-label Phase 1 safety cohort from a planned randomized, placebo-controlled Phase 2 portion. It says the Phase 1 cohort of 5 subjects had been completed and describes a planned Phase 2 portion of 66 subjects. These are design statements in the brief description, not outcome findings. The enrollment recorded for the study is 47; the registry record does not explain the relationship between that enrollment and the Phase 2 plan.

The listed treatment groups include Phase 1 GC4711 plus SBRT, Phase 2 placebo plus SBRT, and Phase 2 GC4711 plus SBRT. The record does not provide a detailed account of sequence generation, allocation concealment, stratification, or the exact roles masked. It therefore supports describing the study as randomized and triple-masked as registered, but not specifying how those procedures were implemented.

The study began on 2020-10-18, and the primary completion date is 2023-11-28. Neither date establishes that all intended follow-up or analyses were completed. The record does not report why the study was terminated, whether termination affected enrollment or follow-up, or whether participants continued assessments after the termination decision. Those details are not reported in the registry record.

The recorded primary endpoint is a participant count for complete or partial in-field tumor response based on RECIST 1.1. Imaging was planned at baseline and at follow-up times named in the outcome description. Although the design sets out a comparison between GC4711 plus SBRT and placebo plus SBRT in Phase 2, the registry record does not report a primary-outcome analysis or a treatment-effect estimate.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat population includes all subjects enrolled/randomized to the 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 Percent of Patients With a Complete Response or Partial In-field Tumor Response Based on the RECIST 1.1 Criteria Through 6 Months Following SBRT., measured over 6 months, 12 months, 18 months and 24 months post SBRT and GC4711+Placebo.

The primary endpoint concerns the number of participants with a complete response or partial in-field tumor response, assessed using RECIST 1.1. The outcome title specifies response through 6 months following SBRT. Its timeframe also lists assessments at 6 months, 12 months, 18 months, and 24 months post SBRT and GC4711 or placebo. The description says participants had a baseline CT of the chest, abdomen, and pelvis and were reassessed using the same imaging modality. Each assessment was compared with the previous best response.

In general, an imaging response endpoint converts measurements or assessments of tumor change into defined categories. Using stated criteria can make the assessment more consistent than an informal judgment, while the focus on in-field response limits the endpoint to tumor response within the treated field. A count of participants with complete or partial response describes how many meet those categories; by itself, it does not quantify the size of tumor change or establish a causal treatment effect.

The registry record identifies the Intent to Treat population as all subjects enrolled or randomized. It does not report response counts, group-specific denominators for the primary endpoint, missing imaging assessments, or the method used to handle participants without an evaluable assessment. It also does not clarify how the endpoint title’s 6-month period relates to the additional listed follow-up times. Thus, the endpoint’s intended measurement is described, but its observed result and analysis details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General statistical context: Randomization assigns participants to study groups using a chance-based process. When implemented as planned, it can help balance both known and unknown participant characteristics across groups, supporting a fair comparison. It does not guarantee identical groups, and it cannot correct problems caused by incomplete outcome measurement, deviations from assigned treatment, or selective reporting. GRECO-1 is recorded as randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record.

The registered design is parallel-group, meaning the listed groups are separate rather than each participant receiving both study treatments in sequence. The Phase 2 comparison is GC4711 plus SBRT versus placebo plus SBRT. The Phase 1 group is described separately as an open-label safety cohort, so its role should not be conflated with the randomized Phase 2 comparison.

What does masking mean in this record?

The registry record labels the study triple-masked. In general, masking can reduce the influence of treatment knowledge on participant behavior, clinical care, outcome assessment, or analysis, depending on who is masked. The exact people or roles covered by the triple-masking designation are not reported in the registry record. The Phase 1 cohort is explicitly described as open-label, so the masking statement should not be applied to that cohort without further information.

How should the response count be understood?

The primary outcome is a count of participants with complete or partial in-field tumor response according to RECIST 1.1. A binary response endpoint classifies each participant as meeting or not meeting the specified response definition for a particular analysis. General statistical context: a count is interpretable alongside its denominator; the count alone does not show the proportion of an arm meeting the endpoint. The registry record does not report primary-outcome group counts or denominators, so no response rate or between-group comparison can be described.

The record describes imaging at baseline and reassessment with the same modality. It also names multiple follow-up times and says each assessment was compared with the previous best response. General statistical context: repeated assessments on the same participant are related rather than independent. An analysis needs to define which visit or response history answers the primary question, how participants with incomplete assessment are handled, and whether repeated measurements are modeled jointly or analyzed separately. Those details are not reported in the registry record.

What can a confidence interval tell a reader?

General statistical context: A confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval spanning values that represent materially different effects may leave the magnitude uncertain. A confidence interval does not by itself establish that an analysis is unbiased or that a result is clinically important. No primary-outcome estimate or confidence interval is reported in the registry record, so precision of the treatment comparison cannot be assessed.

What does a significance test address?

General statistical context: A significance test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. Its interpretation depends on the analysis plan, data quality, and how many outcomes or comparisons were examined. The registry record reports no primary-outcome p-value or analysis result.

Why can over-dispersion matter?

General statistical context: Over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors can be too small and confidence intervals too narrow, making statistical evidence appear more precise than it is. Whether over-dispersion is relevant depends on the outcome and model. The primary endpoint is described as a participant count, but no model, dispersion estimate, or primary analysis is reported in the registry record. It would therefore be speculative to claim that over-dispersion was tested or affected the results.

How should the planning illustration be read?

The registry record describes a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, and that non-time-to-event illustrations are expressed as participants per arm. No illustration values or underlying primary-outcome effect are reported in the registry record. In general, a sample-size illustration describes assumptions for a hypothetical future design; it is not a count of participants observed in this study and does not measure the study’s observed power. Such an illustration also cannot replace a reported treatment-effect estimate and uncertainty interval.

The record does not report the trial’s own sample-size justification or statistical analysis plan. The planning assumptions described for an illustration should therefore be distinguished from the methods actually prespecified or used in GRECO-1, which are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description names several follow-up times: 6 months, 12 months, 18 months, and 24 months post-treatment. The title emphasizes response through 6 months, but the record does not clarify how the later assessments relate to the primary endpoint. It does not report whether each time was treated as a separate test, whether one time was designated as primary and others as secondary, or whether an adjustment for multiple comparisons was planned or used. Multiplicity procedures are not reported in the registry record.

General statistical context: When several outcomes, time points, subgroups, or comparisons are tested, the chance of obtaining at least one apparently notable result can increase. Prespecifying a primary analysis and, where appropriate, using a multiplicity strategy can help keep interpretation aligned with the intended question. Without the analysis plan and results, the degree to which multiplicity was addressed cannot be assessed.

The primary population is described as the Intent to Treat population, including all subjects enrolled or randomized. However, the record does not state how participants with missing scans, incomplete follow-up, withdrawal, or other unavailable outcome data were handled. It does not report the amount or pattern of missing primary-outcome data, imputation methods, sensitivity analyses, or whether the analysis population differed from the stated Intent to Treat definition.

The record also does not report the detailed statistical analysis plan, including the primary comparison method, covariate adjustment, treatment of protocol deviations, or handling of repeated response assessments. These omissions limit assessment of whether analyses followed a prespecified plan and how robust any eventual result would be. Since no primary-outcome analysis is reported in the registry record, readers cannot evaluate the consequences of missingness or multiplicity for the treatment comparison.

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: cerebrovascular accident (14.3%), cardiac arrest (5.0%), pericardial effusion (5.0%), cholecystitis acute (5.0%), pneumonia (5.0%).

The registry record reports safety counts for Phase 1, Phase 2 placebo plus SBRT, and Phase 2 GC4711 plus SBRT. The serious-adverse-event counts are 1 in each group, with the corresponding at-risk counts listed as 7, 20, and 20. Other-adverse-event counts are 7, 20, and 19, with at-risk counts of 7, 20, and 20. Death counts are 0, 1, and 2, respectively. These figures are descriptive; the record does not report a comparative safety analysis or confidence intervals.

The listed serious adverse event terms include cerebrovascular accident at 14.3%, and cardiac arrest, pericardial effusion, acute cholecystitis, pneumonia, and sepsis at 5.0% each. The registry record does not explain the term-specific denominators, attribution rules, or whether events could be counted in more than one category. These percentages should therefore be read as reported, not recalculated or used to infer comparative risk.

General statistical context: Event counts depend on the number of participants assessed, the observation period, and the event definitions. A count does not show how long each participant was followed, and small group counts can be imprecise. The record does not report enough detail to establish whether the groups had comparable observation time or to determine causality. The Phase 1 group is open-label in the study description and should be kept distinct from the randomized Phase 2 groups when interpreting these safety data.

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

The record identifies the question GRECO-1 was designed to address: whether adding GC4711 to SBRT changes the number of participants with complete or partial in-field response under RECIST 1.1, compared with placebo plus SBRT in Phase 2. It also records the trial’s Phase I/II status, randomized design, triple-masking designation, enrollment of 47, and terminated status. These details describe the registered study, not its efficacy result.

No primary-outcome counts by treatment group, effect estimate, confidence interval, or p-value are reported in the registry record. As a result, the posted information does not establish the direction or magnitude of any treatment-group difference, or how precisely such a difference might be estimated. Lack of a reported result is not evidence that the treatments had the same outcome, nor does it show that one was better.

The safety figures provide event counts for the listed groups, but they are not a substitute for a comparative safety analysis. Differences in follow-up, event ascertainment, or group composition could affect descriptive counts; the record does not provide details needed to evaluate those possibilities. The counts alone also do not establish whether an event was caused by study treatment.

The record’s endpoint description includes several follow-up times, while its title focuses on response through 6 months. It does not explain how these time points were prioritized or analyzed, and does not report how missing assessments were handled. The terminated status likewise lacks an explanation of the reason for termination or its impact on follow-up and analysis.

In general, a clinical trial result is best understood through the outcome definition, the comparison estimate, its uncertainty, and the analysis population. Those primary comparison results are not reported in the registry record. The available information therefore supports a careful account of study design and selected safety counts, but not a conclusion about treatment efficacy or comparative safety.

13. Why This Trial Matters Statistically

GRECO-1 is statistically notable as a registered Phase I/II study that separates an open-label safety cohort from a randomized, placebo-controlled Phase 2 comparison. Keeping those components distinct matters because they address different questions and have different design features. The Phase 1 cohort is described as open-label, whereas the Phase 2 portion is described as randomized and placebo-controlled.

The primary endpoint is an imaging-based participant count, framed as complete or partial in-field response under RECIST 1.1. This makes the endpoint definition, visit schedule, and handling of missing scans important to interpretation. The record names more than one assessment time but does not report how they fit into the primary analysis. A clearly specified analysis is particularly important when response is assessed repeatedly over follow-up.

The record also illustrates the distinction between a trial’s planned enrollment and its recorded enrollment. The brief description states a Phase 2 plan of 66 subjects, while the registry enrollment is 47 and the study status is terminated. Those details alone do not explain the study’s course or establish the impact on statistical precision. The reason for termination, the outcome-data completeness, and the analysis plan are not reported in the registry record.

Finally, descriptive safety counts and a design description cannot replace a comparative efficacy analysis. Without primary-outcome estimates and uncertainty measures, the central treatment comparison remains unquantified in the record. This makes transparent reporting of analysis populations, follow-up completeness, and the prespecified role of each endpoint essential for readers assessing what the trial can establish.

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 central limitation is that the registry record does not report the primary-outcome analysis. There are no group-specific response counts, treatment-effect estimate, confidence interval, or test result with which to assess the main comparison. The record describes the endpoint but does not show its observed result.

The primary-outcome title focuses on response through 6 months, while its timeframe lists assessments at 6 months, 12 months, 18 months, and 24 months. The record does not clarify the relationship between these time points or identify how they were handled analytically. It also does not report the number of participants with evaluable imaging at each assessment or how missing scans were addressed.

The trial is recorded as terminated, with enrollment of 47. The brief summary describes a Phase 2 plan of 66 subjects and a completed Phase 1 safety cohort of 5 subjects, but the record does not explain the relationship between these statements and the final enrollment, or why termination occurred. It does not say whether termination changed planned follow-up, enrollment, or analysis.

Important design and analysis details are also absent. The randomization procedure, allocation concealment, exact masking roles, sample-size justification, statistical analysis plan, multiplicity approach, and analysis of repeated assessments are not reported in the registry record. The safety results are counts without a reported comparative analysis, uncertainty measures, or sufficient event-attribution detail. These limitations restrict what can be inferred from the registered information and prevent a full assessment of the study’s primary statistical evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC — NCT04476797.
• Registry record last updated 2024-04-30; status last verified 2023-12.
• Results first posted 2024-04-03.
• 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

GRECO-1 is registered as a Phase I/II randomized, placebo-controlled, parallel-group study of GC4711 plus SBRT for centrally located or large, node-negative NSCLC. The registry record lists triple masking, enrollment of 47, and terminated status. The brief description distinguishes an open-label Phase 1 safety cohort from a planned Phase 2 comparison of GC4711 plus SBRT with placebo plus SBRT.

The primary endpoint is the number of participants with complete or partial in-field tumor response based on RECIST 1.1. The outcome title emphasizes response through 6 months, and the timeframe also lists later assessments. Primary-outcome group results and statistical comparisons are not reported in the registry record.

Safety counts are reported for the Phase 1 and Phase 2 groups, including serious adverse events, other adverse events, and deaths. The record does not report a comparative safety analysis, the reason for termination, or detailed methods for missing data, multiplicity, and primary-outcome analysis. Accordingly, the registered information describes the study and selected safety findings but does not establish the primary treatment comparison.