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 Safety Study of Nivolumab to Treat Advanced or Metastatic Non-small Cell Lung Cancer (NCT03090737), a na phase 2 study. The primary outcome is The Number of Participants Experiencing High Grade (Grades 3-4 and Grade 5) Drug-Related Select Adverse Events (AE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03090737 |
| Phase | Phase 2 |
| Condition | Non-Small Cell Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 129 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced or metastatic non-small cell lung cancer whose disease had progressed during or after at least one prior systemic regimen. The primary outcome population is described as all treated participants. Further participant characteristics are not reported in the registry record.
Intervention
Nivolumab, administered on specified days. The adverse-event record lists a group titled “Nivolumab 480mg Q4W.” Details beyond that regimen description are not reported in the registry record.
Comparator
No comparator group is listed. This is an open-label, single-group study, so the registry record does not present a randomized comparison with another treatment or a control condition.
Primary question
How many treated participants experienced at least one select adverse event of Grade 3, Grade 4, or Grade 5 that the investigator judged related to study drug, within the stated treatment-related observation window? The primary outcome result is not reported in the registry record.
3. Trial Design
The registry describes NCT03090737 as a Phase II, open-label, single-group study of nivolumab. Its official title identifies the population as participants with advanced or metastatic non-small cell lung cancer who had progressed during or after receiving at least one prior systemic regimen. The listed intervention is nivolumab; no comparator arm is listed. Allocation is recorded as NA and masking as none.
The registry lists enrollment of 129 and a status of completed. The recorded start date is 2017-06-02, and the primary completion date is 2021-02-16. The sponsor is Bristol-Myers Squibb. The adverse-event group is titled “Nivolumab 480mg Q4W,” while the arm description states “Specified Dose on Specified Days.” Further dosing details are not reported in the registry record.
The primary outcome concerns high-grade drug-related select adverse events. The registry also lists progression-free survival, objective response rate, overall survival, and duration of response as secondary outcomes. Although six outcome measures are recorded, the registry record lists zero analyses. Results for the primary and secondary outcomes are not reported in the registry record. The record does not describe a randomized treatment contrast, so it cannot by itself estimate a comparative treatment effect against a control group.
The registry does not report the rationale for the planned enrollment, a statistical analysis plan, or interim analyses. The enrolled number should therefore be read as the recorded enrollment, not as evidence that a particular sample-size justification or analysis strategy was used.
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
| Stage | Nivolumab 480mg Q4W |
|---|---|
| STARTED | 129 |
| COMPLETED | 0 |
| NOT COMPLETED | 129 |
Reasons for not completing this period:
| Reason | Nivolumab 480mg Q4W |
|---|---|
| Other reasons | 1 |
| Completed treatment as per protocol | 17 |
| Maximum clinical benefit | 2 |
| Adverse event unrelated to study drug | 7 |
| Study drug toxicity | 4 |
| Disease progression | 98 |
Analysis population for the primary outcome, as defined in the registry: All Treated Participants
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 | Nivolumab 480mg Q4W |
|---|---|---|
| Participants analysed | 129 | |
| Age, Continuous | Years | 61.8 (SD 10.2) |
| Sex: Female, Male: Female | Participants | 34 |
| Sex: Female, Male: Male | Participants | 95 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 41 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 87 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 26 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 95 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as The Number of Participants Experiencing High Grade (Grades 3-4 and Grade 5) Drug-Related Select Adverse Events (AE), measured over From the first dose of study treatment to up to 30 days of the last dose of study treatment (up to 24 months).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants who experienced at least one select adverse event of Grade 3 to Grade 5 that the investigator judged related to study drug. The event had to begin on or after the first dose and within 30 days of the last dose. The stated timeframe extends from the first dose to up to 30 days after the last dose, described as up to 24 months. The population is all treated participants.
The listed select-event categories include pulmonary, gastrointestinal, hepatic, renal, skin, and endocrine events, including thyroid disorders, diabetes, pituitary, and adrenal disorder subcategories. The registry defines Grade 3 as severe or medically significant but not immediately life-threatening, Grade 4 as life-threatening with urgent intervention indicated, and Grade 5 as death related to the adverse event. The grading system is NCI CTCAE v4.0.
A count of participants with at least one qualifying event is a binary-outcome summary: each participant either meets the event definition or does not. Such an endpoint can describe the observed burden of specified high-grade events in the treated group. It does not, without a comparator and an appropriate analysis, establish how that burden differs from another treatment or from what would have occurred otherwise. The primary outcome result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry defines a clinically specific safety outcome: participants must have experienced at least one event from selected categories, the event must be Grade 3 to Grade 5, and the investigator must judge it related to study drug. The observation window begins with the first dose and extends through 30 days after the last dose, with a stated maximum timeframe of up to 24 months. These rules determine which events count for the primary outcome; they do not indicate how many participants met the definition.
The primary outcome is a participant count, and the record identifies all treated participants as its population. However, the primary outcome result is not reported in the registry record. The adverse-event information separately lists 129 at risk and 56 affected for serious adverse events, along with 129 at risk and 111 affected for other adverse events. Those counts should not be substituted for the primary endpoint: the available record does not establish that the affected participants had the particular high-grade, select, investigator-attributed drug-related events required by the primary definition.
The registry records 105 deaths in the adverse-event data. That count does not, by itself, establish that deaths were caused by study drug or met the primary outcome definition. The primary outcome includes Grade 5 events only when the death is related to the adverse event, and the record does not provide a breakdown connecting the deaths to that definition.
Serious-event terms and percentages are also listed, including malignant neoplasm progression at 28.7%, pneumonia at 4.7%, pneumothorax at 1.6%, anaemia at 0.8%, pancytopenia at 0.8%, and cardiac tamponade at 0.8%. These descriptions identify reported serious-event terms; they are not estimates of the primary endpoint. The registry record does not report the denominator or analysis details associated with each listed percentage, so their scope should not be extended beyond the record's presentation.
Because this is a single-group study without a listed comparator, its outcome data can describe events recorded in the treated group but cannot isolate a treatment effect from other explanations. The registry record also does not report confidence intervals, hypothesis tests, or outcome analyses. Consequently, the precision and statistical uncertainty of the primary endpoint cannot be assessed from the recorded primary result, which is absent.
9. Statistical Methods Explained
What does the primary outcome count?
It counts participants, rather than all event episodes. A participant qualifies if at least one event satisfies the registry's criteria: the event is in a specified select category, reaches Grade 3 to Grade 5, is judged by the investigator to be related to study drug, and has an onset within the specified window. A participant with multiple qualifying events would still meet the participant-level definition; the endpoint is not described as a count of all event episodes.
In general, participant-level event outcomes are binary: each person is classified as having met the definition or not. A count can convey how many participants met it, while a proportion uses the number assessed as its denominator. The registry describes the primary outcome as a count and says it is divided by the number of treated participants in its description. However, a primary result is not reported in the registry record, so neither the reported count nor a resulting proportion is available.
How should the event window and grading be understood?
The primary outcome's window begins on or after the first dose and runs through 30 days after the last dose; the overall timeframe is described as up to 24 months. Events outside the stated onset window are not part of this endpoint as defined. The registry identifies NCI CTCAE v4.0 as the grading criteria and describes Grade 3 as severe or medically significant but not immediately life-threatening, Grade 4 as life-threatening with urgent intervention indicated, and Grade 5 as death related to an adverse event. These are the endpoint's classification rules, not a report of event frequency.
Investigator attribution is also part of the definition. The endpoint therefore includes an assessment of whether an event was related to study drug, not merely whether the event occurred after treatment began. The registry record does not report further details about attribution procedures or how disagreements, if any, were handled.
What can a single-group design estimate?
In general, a single-group study can describe outcomes observed among participants receiving the listed intervention. With no concurrent comparator group, it cannot directly estimate a between-group difference. Changes or events in the group cannot automatically be attributed to treatment, because the design does not provide a randomized control comparison to separate treatment effects from other possible influences.
This study is identified as open-label, single-group, and Phase II. Allocation is recorded as NA, masking as none, and no comparator arm is listed. The registry record does not report a different design feature that would create a control comparison. The results should therefore be interpreted as descriptive observations in the study group, not as comparative evidence.
What do confidence intervals and tests contribute in general?
In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified method and assumptions. A narrower interval indicates greater precision under those conditions, while a wider interval indicates less precision. A hypothesis test evaluates data against a stated null hypothesis and model. Neither method replaces the need to understand the outcome definition, the analysis population, and the study design.
The registry record does not report a confidence interval, hypothesis test, or primary outcome analysis. Statistical uncertainty around the primary endpoint therefore cannot be described from the registry entry. The absence of a reported analysis is not evidence that the outcome was zero or that no events occurred.
How should planning illustrations be distinguished from trial results?
In general, sample-size calculations are prospective planning exercises that depend on assumptions about the effect to detect, significance level, allocation, and statistical method. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. It also distinguishes event totals for time-to-event planning from participants per arm for other outcomes.
Those assumptions describe a planning illustration, not the design of this single-group trial. The illustration is not an observed-power result, and it does not establish that the trial was designed or analyzed using those assumptions. The registry record does not report the trial's own sample-size justification, nor does it provide a primary outcome analysis from which to assess a trial-specific effect. Any planning illustration should therefore be kept separate from the observed enrollment of 129 and from the unreported primary endpoint result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures and identifies progression-free survival, objective response rate, overall survival, and duration of response as secondary outcomes. It lists zero analyses. The primary outcome is the count of participants with high-grade drug-related select adverse events, but its result is not reported in the registry record. Results for the named secondary outcomes are also not reported in the registry record.
When a study evaluates multiple outcomes, multiplicity can arise because conducting several statistical tests may increase the chance of at least one apparently unusual finding under a set of null hypotheses. In general, an analysis plan may specify a hierarchy or adjustment approach to address that issue. The registry record does not report whether multiplicity was addressed, which outcomes were formally tested, or whether any adjustment was used. No correction method should be inferred from the listed outcomes alone.
Missing-data handling is not reported in the registry record. The entry does not describe how participants who stopped treatment, had incomplete follow-up, or lacked an outcome assessment were handled in analyses. The record identifies all treated participants as the primary outcome population, but it does not report an analysis population for the secondary outcomes or provide details about exclusions and denominators. The available record therefore does not allow assessment of how missing observations might affect the reported outcomes.
Interim analyses and any associated decision rules are not reported in the registry record. Nor does the registry entry provide an inferential analysis plan, confidence intervals, or test results. These omissions limit assessment of the statistical methods used; they do not establish that a particular method was or was not used outside what the record reports.
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 |
|---|---|---|---|
| Nivolumab 480mg Q4W | 56 | 129 | 43.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nivolumab 480mg Q4W | 105 of 129 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nivolumab 480mg Q4W | 111 of 129 |
Most frequent serious adverse event terms
| Event term | Organ system | Nivolumab 480mg Q4W |
|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 37 of 129 |
| Pneumonia | Infections and infestations | 6 of 129 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 2 of 129 |
| Anaemia | Blood and lymphatic system disorders | 1 of 129 |
| Pancytopenia | Blood and lymphatic system disorders | 1 of 129 |
| Cardiac tamponade | Cardiac disorders | 1 of 129 |
| Colitis | Gastrointestinal disorders | 1 of 129 |
| Nausea | Gastrointestinal disorders | 1 of 129 |
| Oesophageal ulcer | Gastrointestinal disorders | 1 of 129 |
| Vomiting | Gastrointestinal disorders | 1 of 129 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nivolumab 480mg Q4W |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 37 of 129 |
| Blood alkaline phosphatase increased | Investigations | 32 of 129 |
| Rash | Skin and subcutaneous tissue disorders | 26 of 129 |
| Diarrhoea | Gastrointestinal disorders | 24 of 129 |
| Pruritus | Skin and subcutaneous tissue disorders | 24 of 129 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 23 of 129 |
| Nausea | Gastrointestinal disorders | 22 of 129 |
| Decreased appetite | Metabolism and nutrition disorders | 21 of 129 |
| Fatigue | General disorders | 19 of 129 |
| Headache | Nervous system disorders | 17 of 129 |
Serious events with the highest arm-level rate: malignant neoplasm progression (28.7%), pneumonia (4.7%), pneumothorax (1.6%), anaemia (0.8%), pancytopenia (0.8%).
The adverse-event record lists 129 participants at risk and 56 affected for serious adverse events. It separately lists 129 at risk and 111 affected for other adverse events. The entry also reports 105 deaths. These are distinct adverse-event summary figures and should not be treated as interchangeable with the primary endpoint count. The primary endpoint specifically requires a Grade 3 to Grade 5 select event judged related to study drug, within its defined observation window. The record does not provide a result for that endpoint.
The registry lists malignant neoplasm progression at 28.7%, pneumonia at 4.7%, pneumothorax at 1.6%, anaemia at 0.8%, pancytopenia at 0.8%, and cardiac tamponade at 0.8% among the top serious-event terms. These are reported percentages for listed terms; the registry record does not give their denominators or additional analysis details. They should not be read as causal estimates or as the proportions meeting the primary endpoint definition.
In general, safety counts and percentages depend on event definitions, follow-up, and the population used as the denominator. A count of deaths alone does not indicate their cause or relation to treatment. The record does not provide a death-cause breakdown or establish that all listed serious events were judged related to nivolumab.
12. What the Result Does, and Does Not, Mean
The registry describes a completed Phase II study of nivolumab in a single group of participants with advanced or metastatic non-small cell lung cancer who had progressed during or after at least one prior systemic regimen. Its primary safety outcome was defined around high-grade, select adverse events judged related to study drug. The adverse-event record includes counts of affected participants and listed serious-event terms, but the primary endpoint result itself is not reported in the registry record.
These data do not establish how the primary outcome compares with outcomes under another treatment, because no comparator group is listed. A single-group count can describe events recorded among treated participants, but without a control group it cannot show what the event burden would have been under an alternative treatment or without the study intervention. It also cannot, by itself, separate treatment-related events from events arising from the disease or other factors.
The 56 serious-adverse-event-affected participants, 111 other-adverse-event-affected participants, and 105 deaths are adverse-event summary figures, not the missing primary outcome result. The primary endpoint has additional requirements concerning event grade, event category, investigator attribution, and timing. The registry does not report whether the listed counts overlap or how the deaths relate to the primary endpoint definition. The serious-event term percentages likewise should not be interpreted as treatment effects or as primary endpoint rates.
In general, estimates are more informative when their uncertainty and analysis population are reported alongside their definitions. The registry entry does not report a primary outcome estimate, confidence interval, or hypothesis test. Thus the precision of the primary outcome cannot be assessed, and no statistical conclusion about a comparative effect can be drawn from this record. The listed secondary outcomes do not have reported results in the registry record either.
13. Why This Trial Matters Statistically
This study illustrates why statistical interpretation begins with the design and endpoint definition, not just with event counts. A safety endpoint can require several conditions at once: event category, severity grade, investigator attribution, and timing relative to treatment. Counts for broad serious or other adverse-event summaries cannot stand in for an endpoint with narrower criteria. Keeping these definitions separate prevents an over-reading of safety summaries.
The single-group design also sets a clear boundary on interpretation. It can describe observations in participants who received nivolumab, but it does not provide a randomized comparator for estimating a treatment contrast. The distinction matters whenever readers are tempted to treat an event count as evidence about what treatment caused or prevented. In this record, the absence of a listed comparator is a design feature, not a minor analytical detail.
Finally, a completed study record does not necessarily provide all outcome estimates or their uncertainty. Here, the registry identifies the primary outcome and lists adverse-event summaries, but the primary outcome result and statistical analyses are not reported in the registry record. Recognizing what is defined, what is counted, and what remains unreported is part of sound biostatistical reading. It avoids turning descriptive safety information into an unsupported comparative claim.
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 primary limitation for interpreting the stated research question is that the primary outcome result is not reported in the registry record. The record defines the endpoint and its population, but does not provide the count of participants who met that definition, a proportion, or an uncertainty estimate. A reader therefore cannot assess the observed frequency or its statistical precision from the primary result.
The study is single-group and has no listed comparator. Accordingly, it does not support a direct randomized comparison of safety outcomes across treatments. The record's adverse-event summaries do not resolve that limitation, and they do not establish that events or deaths were caused by nivolumab.
Additional interpretation is constrained because the registry does not report the analysis methods, missing-data handling, interim analyses, or sample-size justification. It also does not report detailed analysis populations for the secondary outcomes, or denominators and analysis details for the listed serious-event percentages. The registry lists six outcome measures but zero analyses, and results for the named secondary outcomes are not reported in the registry record.
The registry describes an all-treated population for the primary endpoint and an adverse-event group with 129 at risk. It does not provide enough detail to determine how follow-up completeness, treatment discontinuation, or outcome ascertainment affected the available summaries. These limitations concern what can be evaluated from the registry record; they do not establish that the study lacked procedures or analyses that are not described there.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of Nivolumab to Treat Advanced or Metastatic Non-small Cell Lung Cancer — NCT03090737.
- Registry record last updated 2022-12-05; status last verified 2022-12.
- Results first posted 2022-03-14.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT03090737 is a completed, Phase II, open-label, single-group study sponsored by Bristol-Myers Squibb. It evaluated nivolumab in participants with advanced or metastatic non-small cell lung cancer whose disease had progressed during or after at least one prior systemic regimen. Recorded enrollment was 129; the study start date was 2017-06-02 and the primary completion date was 2021-02-16.
The primary outcome was the count of treated participants with at least one Grade 3 to Grade 5 select adverse event judged related to study drug within the specified treatment-related window. The registry lists serious and other adverse-event summaries, serious-event terms, and secondary outcome names. The primary outcome result, secondary outcome results, and statistical analyses are not reported in the registry record. Because no comparator is listed, the design supports description of the study group rather than a randomized between-treatment comparison.