This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Survival Prolongation by Rationale Innovative Genomics (NCT03386929), a na phase 1, phase 2 study. The primary outcome is Incidence of the Tested 3-Drug Combination Therapy-Emergent Adverse Events and Serious Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03386929 |
| Phase | Phase 1, Phase 2 |
| Condition | Non-small Cell Lung Cancer Metastatic, Non-small Cell Lung Cancer Stage IIIB |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Worldwide Innovative Network Association |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with advanced or metastatic non-small cell lung cancer (NSCLC) and no documented targetable alterations. The listed alterations include EGFR mutation, ALK translocation, ROS1 mutation if available, and MET exon 14 skipping mutation if available. The registry also lists metastatic NSCLC and stage IIIB NSCLC as conditions.
Intervention
The planned treatment was a combination of avelumab, axitinib and palbociclib. The record describes dosing for Phase 1: avelumab by intravenous administration on days 1 and 15 of a 28-day cycle, axitinib orally twice daily every day of the cycle, and palbociclib orally on days 8 through 28. Phase 2 dosing details are not reported in the registry record.
Comparator
There was no separate control group. The study is recorded as single-group, with allocation listed as not applicable and masking listed as none. Dose levels are recorded, but they do not constitute a like-for-like control comparison. The registry record does not describe a randomized comparison.
Primary question
The planned primary outcome was the incidence of treatment-emergent adverse events and serious adverse events for the tested three-drug combination. The outcome period ran from informed-consent signature through 90 days after the last treatment dose. The registry states that this outcome could not be measured because data were not collected after early termination following Phase 1; Phase 2 was not started.
3. Trial Design
This was a Phase 1 and Phase 2 study, recorded as a single-group, non-masked trial with allocation listed as not applicable. The registry describes a proof-of-concept study in advanced or metastatic NSCLC. Its stated aims included exploring the safety and efficacy of the three-drug approach and retrospectively assessing whether integrated genomic and transcriptomic information could match patients to the combination. Those aims do not mean that the registry reports results for either aim.
The planned regimen combined avelumab, axitinib and palbociclib. For Phase 1, avelumab was administered intravenously on day 1 and day 15 of a 28-day cycle; axitinib was taken orally twice daily every day of that cycle; and palbociclib was taken orally on days 8 through 28. The Phase 2 arm description is incomplete in the registry record, so its dosing details are not reported in the registry record.
The registry lists enrollment of 15 and records three dose levels. The safety entries are organized by dose level, not by randomized treatment assignment. The record gives no basis for treating the dose levels as independent, comparable treatment groups or for interpreting differences between them as causal effects.
The study began on 2017-11-29, had a primary completion date of 2022-12-29, and is listed as terminated. The registry states that termination occurred after the end of Phase 1 and that Phase 2 did not start. Consequently, the planned primary outcome was not measured, and the record does not present efficacy analyses or a completed evaluation of the planned genomic and transcriptomic matching aim.
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: Patients with advanced/metastatic advanced/metastatic non-small cell lung cancer (NSCLC) with no documented targetable alterations (EGFR mutation, ALK translocation, ROS1 mutation if available or MET exon 14 skipping mutation if available) were recruited in the study.
Overall Study
| Stage | Dose Level 1 | Dose Level 2 | Dose Level 3 |
|---|---|---|---|
| STARTED | 6 | 6 | 3 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 6 | 3 |
Reasons for not completing this period:
| Reason | Dose Level 1 | Dose Level 2 | Dose Level 3 |
|---|---|---|---|
| Death | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 1 | 0 |
| Physician Decision | 0 | 0 | 1 |
| Progression | 4 | 4 | 0 |
| Clinical Monitoring Committee and physician choice | 1 | 1 | 1 |
| Transfer to SPRING Rollover protocol (EU CT # 2022-500041-24-00) after closing SPRING | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: This outcome could not be measured because the data were not collected. Indeed, the trial was early terminated after the end of the phase 1. The phase 2 was not started, no data can be reported.
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.
| Characteristic | Unit | Dose Level 1 | Dose Level 2 | Dose Level 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 3 | 15 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 2 | 2 | 7 |
| Age, Categorical: >=65 years | Participants | 3 | 4 | 1 | 8 |
| Age, Continuous | years | 68 (52 to 80) | 67 (51 to 72) | 54 (51 to 76) | 67 (51 to 80) |
| Sex: Female, Male: Female | Participants | 3 | 1 | 1 | 5 |
| Sex: Female, Male: Male | Participants | 3 | 5 | 2 | 10 |
| Race/Ethnicity, Customized: Caucasian | Participants | 6 | 6 | 2 | 14 |
| Race/Ethnicity, Customized: Mexican | Participants | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Black | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 5 | 0 | 2 | 7 |
| Region of Enrollment: Luxembourg | participants | 0 | 2 | 0 | 2 |
| Region of Enrollment: Israel | participants | 0 | 2 | 1 | 3 |
| Region of Enrollment: Spain | participants | 1 | 2 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of the Tested 3-Drug Combination Therapy-Emergent Adverse Events and Serious Adverse Events, measured over From informed consent signature through 90 days after administration of the treatment (last dose).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the incidence of treatment-emergent adverse events and serious adverse events associated with the tested three-drug combination. The specified observation window extended from informed-consent signature through 90 days after the last administration of treatment. The registry says that events were to be summarized for the safety population: participants who received at least one dose of study treatment. Severity assessment was to use NCI CTCAE v4.03, dated June 14, 2010.
An adverse-event endpoint is used to describe the kinds and frequency of unwanted medical events observed during a study period. A serious adverse event is a distinct seriousness classification; it should not be read as synonymous with a high severity grade. The registry names treatment-related and biopsy-related serious adverse events among the secondary outcomes as well.
For this trial, the planned primary endpoint does not have a reported result. The registry explicitly says that the data were not collected because the study ended after Phase 1 and Phase 2 was not started. The dose-level safety entries therefore do not replace a measured primary endpoint: they are separate posted safety figures, and the record does not explain how those entries relate to the intended outcome assessment or its full observation window.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registered primary endpoint has no measured result. The registry says that adverse events and serious adverse events for that outcome could not be measured because data were not collected; early termination followed Phase 1, and Phase 2 did not start. There is therefore no reported estimate for the planned primary outcome over its stated period from informed consent through 90 days after the last dose. This absence is not evidence that no adverse events occurred.
Separate safety figures are posted by dose level. The registry lists serious adverse events affecting 3 of 6 participants at Dose Level 1, 4 of 6 at Dose Level 2, and 2 of 3 at Dose Level 3. It lists other adverse events affecting 6 of 6 at Dose Level 1, 6 of 6 at Dose Level 2, and 3 of 3 at Dose Level 3. These counts describe the record’s dose-level entries. They should not be treated as a randomized comparison, because the study is recorded as single-group and the dose levels are not a like-for-like control comparison.
The record also lists deaths by dose level: 2 at Dose Level 1, 1 at Dose Level 2, and 1 at Dose Level 3. It does not establish in these entries whether a death was caused by treatment. A count of deaths during a study is not, by itself, an attribution of cause or a comparison of risk.
Among the listed serious adverse-event terms are infusion related reaction, neutrophil count decreased, and respiratory failure, each with a registry-listed percentage of 33.3%. Anaemia, coronary artery disease, and disease progression are each listed at 16.7%. These are descriptive entries; the record does not provide enough context to infer an individual participant’s course, a causal relationship, or a comparative treatment effect from the percentages.
No statistical analyses are listed. In particular, the registry does not report a treatment-effect estimate, confidence interval, hypothesis test, or efficacy result. A confidence interval, in general, describes the statistical uncertainty around an estimate; without a reported estimate and interval, the precision of a primary endpoint effect cannot be assessed. The registry’s planned genomic and transcriptomic assessment also has no reported analysis result. Overall, the posted data support a limited description of recorded safety counts, not a conclusion about efficacy or comparative safety.
9. Statistical Methods Explained
The registry record identifies the design as single-group and non-masked, with allocation listed as not applicable. It does not report a randomized treatment assignment or a control group. The dose-level entries should therefore be read as descriptive groupings rather than as evidence from a randomized comparison. In general, random allocation helps balance measured and unmeasured characteristics across groups; without it, observed differences between groups can reflect differences in who was treated, how treatment was delivered, follow-up, or chance. The registry does not report enough detail to evaluate those possibilities for these dose levels.
What does the primary outcome measure?
The registered primary outcome concerns incidence of treatment-emergent adverse events and serious adverse events. Incidence describes the occurrence of events in a defined population over a defined observation period. The stated period begins at informed-consent signature and continues through 90 days after the last treatment dose. The intended safety population includes participants who received at least one dose. The record says that the outcome was to be evaluated using NCI CTCAE v4.03, dated June 14, 2010.
The registry explicitly reports that this primary outcome could not be measured because data were not collected. It attributes this to early termination after Phase 1 and states that Phase 2 was not started. Thus, the definition and planned observation window are available, but an overall estimate for that endpoint is not. The dose-level safety entries are not identified as a complete substitute for the planned primary outcome.
How should counts and percentages be read?
A count of participants with an event is a descriptive quantity. It does not by itself establish that treatment caused the event. A percentage can communicate the proportion represented by a count only when the relevant denominator, event definition, and observation period are clear. The registry gives counts by dose level and lists percentages beside selected serious-event terms, but it does not provide all the context needed to reconstruct how those term percentages were formed. They should be read as the registry’s listed percentages, not recalculated or generalized to a broader population.
Seriousness and severity are related but different concepts. Seriousness generally concerns the consequences or regulatory classification of an event, whereas severity describes its intensity. The registry’s primary outcome mentions both adverse events and serious adverse events and refers to a named grading system. The record does not report event-level grades or a complete assessment of the planned endpoint, so the separate counts should not be interpreted as a full severity profile.
What would a confidence interval add?
In general, a confidence interval gives a range of values compatible with an estimate under a statistical procedure and helps convey its precision. A narrow interval usually indicates more precision than a wide interval, while the interval’s location indicates the values most consistent with the data and method. A confidence interval cannot correct for a missing endpoint, incomplete follow-up, or a non-comparative design. The registry does not report a confidence interval for the primary outcome or a treatment-effect estimate to which one could be attached.
What can the posted analyses establish?
The registry lists no analyses. It does not report a statistical model, adjustment strategy, hypothesis-testing plan, interim analysis, or multiplicity procedure; these details are not reported in the registry record. Without a reported analysis plan and endpoint result, no inferential claim about the treatment combination can be assessed from the primary outcome.
The record lists a sample-size assumption for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It specifies that time-to-event illustrations use the total number of events and other illustrations use participants per arm. Such calculations are planning illustrations, not observed power. They do not change the actual single-group design, and they cannot supply a missing primary endpoint estimate. The registry does not report an observed primary endpoint effect on which to base an interpretation of those planning assumptions.
Finally, the study’s stated proof-of-concept and retrospective matching aims require data and analyses beyond a description of event counts. The record names genomic and transcriptomic profile as a secondary outcome, but no results or analysis are reported. Statistical methods can clarify uncertainty and comparisons only when the underlying outcomes and analysis are available; they cannot recover results that were not collected.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and secondary outcomes concerning treatment-related or biopsy-related serious adverse events and genomic and transcriptomic profile. It does not report a multiplicity strategy. In general, when a study assesses several outcomes or makes several statistical comparisons, a multiplicity plan clarifies how to interpret the chance of false-positive findings across those assessments. Here, the registry lists no analyses, so there are no reported hypothesis tests or adjusted results to interpret. The method for prioritizing or controlling multiple comparisons is not reported in the registry record.
The primary outcome is not simply an outcome with an unreported value: the registry states that it could not be measured because data were not collected. The record links this to early termination after Phase 1 and says Phase 2 was not started. It does not report how much follow-up was available for the dose-level safety entries, whether those entries cover the intended period, or how any incomplete follow-up was handled. The mechanism or pattern of missing data is not reported in the registry record.
The intended safety population is defined as all participants who received at least one dose of study treatment. The registry does not give a separate account of exclusions from that population or an analysis of participants who did not receive a dose. The posted dose-level counts are not described as an analysis of the full intended endpoint population over its complete observation window.
These gaps limit both descriptive completeness and statistical inference. General methods for handling missing observations depend on why data are missing and on what information remains available; the record does not provide enough detail to determine or evaluate such assumptions. No imputation method, sensitivity analysis, or missing-data model is reported in the registry record. As a result, the posted counts cannot be taken as a complete analysis of the primary endpoint or as a basis for resolving uncertainty about unobserved outcomes.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dose Level 1 | 3 | 6 | 50.0% |
| Dose Level 2 | 4 | 6 | 66.7% |
| Dose Level 3 | 2 | 3 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Level 1 | 2 of 6 |
| Dose Level 2 | 1 of 6 |
| Dose Level 3 | 1 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Level 1 | 6 of 6 |
| Dose Level 2 | 6 of 6 |
| Dose Level 3 | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Level 1 | Dose Level 2 | Dose Level 3 |
|---|---|---|---|---|
| Disease progression | General disorders | 1 of 6 | 1 of 6 | 0 of 3 |
| Infusion related reaction | General disorders | 0 of 6 | 2 of 6 | 0 of 3 |
| Anaemia | Blood and lymphatic system disorders | 0 of 6 | 1 of 6 | 0 of 3 |
| Coronary artery disease | Cardiac disorders | 1 of 6 | 0 of 6 | 0 of 3 |
| Fatigue | General disorders | 0 of 6 | 1 of 6 | 0 of 3 |
| General physical health deterioration | General disorders | 1 of 6 | 0 of 6 | 0 of 3 |
| Neutrophil count decreased | Investigations | 0 of 6 | 0 of 6 | 1 of 3 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 6 | 0 of 6 | 0 of 3 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 1 of 6 | 0 of 3 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 0 of 6 | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Level 1 | Dose Level 2 | Dose Level 3 |
|---|---|---|---|---|
| Hypertension | Vascular disorders | 3 of 6 | 4 of 6 | 3 of 3 |
| Fatigue | General disorders | 4 of 6 | 3 of 6 | 1 of 3 |
| Proteinuria | Renal and urinary disorders | 5 of 6 | 2 of 6 | 1 of 3 |
| Neutrophil count decreased | Investigations | 4 of 6 | 3 of 6 | 0 of 3 |
| Platelet count decreased | Investigations | 3 of 6 | 4 of 6 | 0 of 3 |
| Weight decreased | Investigations | 4 of 6 | 2 of 6 | 1 of 3 |
| White blood cell count decreased | Investigations | 4 of 6 | 3 of 6 | 0 of 3 |
| Decreased appetite | Metabolism and nutrition disorders | 3 of 6 | 4 of 6 | 0 of 3 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 6 | 1 of 6 | 3 of 3 |
| Diarrhoea | Gastrointestinal disorders | 3 of 6 | 3 of 6 | 0 of 3 |
Serious events with the highest arm-level rate: infusion related reaction (33.3%), neutrophil count decreased (33.3%), respiratory failure (33.3%), anaemia (16.7%), coronary artery disease (16.7%).
The safety entries are organized by dose level. For serious adverse events, the registry lists 3 of 6 participants at Dose Level 1, 4 of 6 at Dose Level 2, and 2 of 3 at Dose Level 3 as affected. For other adverse events, it lists 6 of 6 at Dose Level 1, 6 of 6 at Dose Level 2, and 3 of 3 at Dose Level 3. The record also lists deaths of 2, 1, and 1 across those dose levels, respectively. These are posted counts, not a randomized comparison or a causal assessment.
The serious-event terms with the largest listed percentages are infusion related reaction, neutrophil count decreased, and respiratory failure, each at 33.3%. Anaemia, coronary artery disease, and disease progression are each listed at 16.7%. The percentages should be read as the registry presents them; the record does not report enough detail alongside these terms to establish a denominator or infer a rate over a particular follow-up period.
These figures are distinct from the planned primary outcome, which the registry says could not be measured because data were not collected. The record does not establish that the listed deaths were treatment-related, and the event counts alone do not establish causation. Nor should the dose-level counts be compared as though participants had been randomly assigned to equivalent groups.
12. What the Result Does, and Does Not, Mean
The record documents a study of avelumab, axitinib and palbociclib in advanced or metastatic NSCLC, with a planned safety-focused primary outcome. It also documents limited safety counts by dose level and lists selected serious adverse-event terms and percentages. These entries can be described as observations recorded in the registry; they are not a complete result for the registered primary endpoint.
The primary endpoint was intended to cover adverse events and serious adverse events from informed consent through 90 days after the final treatment dose. The registry states that the endpoint could not be measured because data were not collected, following early termination after Phase 1. Phase 2 did not start. That means the registered endpoint has no reported estimate in the record. The absence of a measurement should not be mistaken for evidence of no events or for evidence that treatment was safe.
The study was single-group and had no control group. Its dose-level entries cannot establish how outcomes would have differed under another treatment or no study treatment. The counts also cannot, on their own, establish that the treatment caused an event or a death. The registry does not report an efficacy analysis, an effect estimate, or results from the planned genomic and transcriptomic matching assessment.
Thus, the posted information does not answer whether the combination improved clinical outcomes, nor does it provide a complete statistical characterization of its safety under the planned endpoint. It supports a narrower reading: the registry lists dose-level safety counts and selected event terms, while reporting that the primary outcome was not collected. Any further conclusion would require results and analyses that are not reported in the registry record.
13. Why This Trial Matters Statistically
This record illustrates an important distinction between a registered endpoint and an endpoint result. A protocol can define what should be measured, in whom, and over what period, yet the final registry may state that the measurement was not obtained. Here, the primary endpoint has a stated safety population, an observation period, and a grading reference, but the registry says the data were not collected. Statistical interpretation must begin with that gap rather than treating the endpoint definition as if it were a result.
The study also shows why the design matters when reading grouped safety counts. The record identifies a single-group study with no masking and no randomized control comparison. Dose-level counts can describe the posted observations, but they do not offer the same basis for causal inference as a suitably controlled comparison. Differences between dose levels, if considered, could not be separated from other explanations using the registry information alone.
Finally, the study’s stated genomic and transcriptomic matching aim highlights the difference between an ambitious research question and an analyzed result. The registry lists genomic and transcriptomic profile as a secondary outcome but reports no analysis. Without outcome data and an analysis, the matching question remains unanswered in the posted record. For biostatistical interpretation, transparent reporting of non-collection, termination, and the limits of available summaries is essential: it prevents descriptive counts from being mistaken for a complete endpoint evaluation or evidence of comparative benefit.
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 most direct limitation is that the primary adverse-event outcome was not measured. The registry attributes this to early termination after Phase 1 and states that Phase 2 was not started. As a result, the intended endpoint over the period from informed consent through 90 days after the last dose has no reported estimate. The record does not specify how the posted safety counts relate to that full period.
The design was single-group, with no randomized control group and no masking. The dose-level groupings therefore do not provide a like-for-like control comparison. The registry does not report methods that would adjust for differences between dose levels, nor does it report a statistical analysis of the safety entries.
The posted record gives selected event counts, deaths by dose level, and percentages for selected serious-event terms, but does not report enough accompanying detail to establish the event-term denominators or the completeness of follow-up. It does not state whether the listed deaths were treatment-related. No efficacy results or analyses of the genomic and transcriptomic matching aim are reported.
Other details relevant to interpretation—including a statistical analysis plan, interim analyses, multiplicity procedures, missing-data methods, and a sample-size justification—are not reported in the registry record. The Phase 2 dosing description is also not reported in the registry record. These limitations mean that the available entries support only a narrow descriptive reading; they do not provide a complete safety analysis or a comparative estimate of treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Survival Prolongation by Rationale Innovative Genomics — NCT03386929.
- Registry record last updated 2023-12-18; status last verified 2023-11.
- Results first posted 2023-12-18.
- 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.
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18. Record Summary
The registry describes a Phase 1/Phase 2 proof-of-concept study of avelumab, axitinib and palbociclib in advanced or metastatic NSCLC without documented targetable alterations. It records a single-group, non-masked design, enrollment of 15, and three dose levels. Phase 1 dosing is described; Phase 2 did not start.
The trial is listed as terminated. The registry states that it ended after Phase 1 and that the planned primary outcome—the incidence of treatment-emergent adverse events and serious adverse events—could not be measured because data were not collected. Separate safety counts and selected serious-event terms are listed by dose level, but no analyses are reported. The registry does not report efficacy results or results from the genomic and transcriptomic matching aim.