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 Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012) (NCT01454102), a randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01454102 |
| Phase | Phase 1 |
| Condition | Non-small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 472 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
People with stage IIIB/IV non-small cell lung cancer (NSCLC) were the broad study population. The treatment arms included different clinical settings and subgroups: squamous and non-squamous histology, EGFR mutation-positive non-squamous disease, and untreated asymptomatic brain metastases without cerebral edema. The primary outcome population is described as all treated participants.
Intervention
The study evaluated nivolumab given alone or with other treatments. Combination regimens included platinum-based chemotherapy, erlotinib, bevacizumab maintenance, and ipilimumab. Some arms evaluated nivolumab as switch maintenance or in participants with brain metastases. Regimens and treatment settings differed across arms.
Comparator
The registry identifies randomized allocation and a parallel model, but does not report a single common comparator for the many regimens. The arms are not described as one uniform two-treatment comparison. A statistical comparison between specific arms is not reported in the registry record.
Primary question
The primary outcome concerns the number of participants with serious adverse events, adverse events leading to discontinuation, or death. It was intended to characterize safety and tolerability, rather than establish comparative efficacy. The outcome timeframe ran from first dose to 30 days after the last dose of study drug.
The study title and summary describe a broad, multi-arm investigation of nivolumab in NSCLC. Its clinical question was not limited to one combination or one disease subgroup: it covered chemotherapy combinations, targeted therapy, immunotherapy combinations, maintenance strategies, and nivolumab alone. This variety means that arm-level findings need to be read in the context of the regimen and population for that arm. A count from one arm does not, by itself, estimate what would have happened under another regimen.
The record lists objective response rate and progression-free survival rate at Week 24 as secondary outcomes. Those outcomes are distinct from the primary safety question. Their results and comparative analyses are not reported in the registry record summarized by these data. The posted information therefore supports a description of study structure and reported safety counts, not a conclusion about relative benefit among treatment options.
3. Trial Design
This was a Phase I, randomized, unmasked, parallel study sponsored by Bristol-Myers Squibb. The registry lists an enrollment of 472 and a completed status. The recorded study start was 2011-12-16, and primary completion was 2016-07-20. The study title identifies CheckMate 012 and describes nivolumab combinations and monotherapy in people with stage IIIB/IV NSCLC.
The arms covered several treatment approaches. Arms A through D paired nivolumab with platinum-based chemotherapy or bevacizumab maintenance; Arm E paired it with erlotinib; and Arm F evaluated nivolumab alone. Other arms evaluated nivolumab with ipilimumab in squamous, non-squamous, or any histology, while further arms assessed switch maintenance or monotherapy in specific settings. The record includes treatment descriptions with different schedules, including nivolumab given every 2 weeks or every 3 weeks in some arms. These descriptions do not make the regimens interchangeable.
Although allocation is recorded as randomized, the registry record does not describe the randomization procedure, the allocation ratio, or which specific treatment comparisons were planned. Masking is listed as none. The record identifies a parallel model, but it does not report a protocol-level account of how participants were assigned among the many regimens. Details beyond the posted arm descriptions are not reported in the registry record.
The primary outcome is a participant count covering serious adverse events, adverse events leading to discontinuation, or death. Its stated timeframe begins at first dose and continues to 30 days after the last dose of study drug; the registry describes assessment up to July 2016, approximately 55 months. The primary outcome population is all treated participants. Objective response rate and progression-free survival rate at Week 24 are listed as secondary outcomes. The registry record lists no analyses, and does not provide a statistical analysis plan or results for those secondary outcomes.
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: 472 participants were enrolled; 376 participants received at least one dose of study treatment
Only the first 6 of 16 groups are shown.
Overall Study
| Stage | Arm A: Nivolumab + Gemcitabine + Cisplatin | Arm B: Nivolumab + Pemetrexed + Cisplatin | Arm C10: Nivolumab + Paclitaxel + Carboplatin | Arm D: Nivolumab + Bevacizumab Maintenance | Arm E: Nivolumab + Erlotinib | Arm F: Nivolumab |
|---|---|---|---|---|---|---|
| STARTED | 12 | 15 | 15 | 12 | 21 | 52 |
| COMPLETED | 12 | 15 | 15 | 12 | 18 | 49 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 3 | 3 |
Reasons for not completing this period:
| Reason | Arm A: Nivolumab + Gemcitabine + Cisplatin | Arm B: Nivolumab + Pemetrexed + Cisplatin | Arm C10: Nivolumab + Paclitaxel + Carboplatin | Arm D: Nivolumab + Bevacizumab Maintenance | Arm E: Nivolumab + Erlotinib | Arm F: Nivolumab |
|---|---|---|---|---|---|---|
| Continuing in the treatment period | 0 | 0 | 0 | 0 | 3 | 3 |
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.
Only the first 6 of 17 groups are shown.
| Characteristic | Unit | Arm A: Nivolumab + Gemcitabine + Cisplatin | Arm B: Nivolumab + Pemetrexed + Cisplatin | Arm C10: Nivolumab + Paclitaxel + Carboplatin | Arm D: Nivolumab + Bevacizumab Maintenance | Arm E: Nivolumab + Erlotinib | Arm F: Nivolumab |
|---|---|---|---|---|---|---|---|
| Participants analysed | 12 | 15 | 15 | 12 | 21 | 52 | |
| Age, Continuous | years | 66.2 (SD 6.82) | 60.2 (SD 11.20) | 58.7 (SD 8.81) | 62.9 (SD 9.53) | 62.8 (SD 9.41) | 67.0 (SD 9.96) |
| Sex: Female, Male: Female | Participants | 5 | 9 | 8 | 5 | 13 | 26 |
| Sex: Female, Male: Male | Participants | 7 | 6 | 7 | 7 | 8 | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death, measured over From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 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 serious adverse events, adverse events leading to discontinuation, or death. It is a safety and tolerability measure, not a direct measure of tumor response or time to progression. The registry defines an adverse event as a new unfavorable symptom, sign, or disease, or worsening of a pre-existing condition, which may not have a causal relationship with treatment. A serious adverse event is a medical event meeting the serious criteria described in the record, including events that result in death, are life-threatening, require or prolong hospitalization, or meet other listed criteria.
Counting participants with these events can help describe the burden of serious harm or treatment interruption during follow-up. It is useful in a Phase I study because early evaluation of safety and tolerability is central to examining treatment regimens. However, a participant count alone does not convey event duration, severity distribution, timing, or whether an event was judged related to study drug. The record defines treatment-relatedness categories, but the primary outcome title includes events without limiting them to events judged treatment-related.
The timeframe is from first dose to 30 days after the last dose of study drug, with assessment described as up to July 2016, approximately 55 months. The posted outcome description does not provide a single reported primary endpoint result or an arm-level breakdown for every component of the composite outcome. The registry record therefore does not support a complete comparison of the composite outcome across all treatment arms.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available results are principally arm-level safety counts. For the reported groups, the registry gives the number at risk and the number affected in serious-event and other adverse-event categories. Those counts describe what was recorded for participants in each listed group; they are not, on their own, estimates of a causal treatment effect. The arms differ in treatment combinations and clinical settings, so an unadjusted contrast between two arm counts would not establish that the treatments caused a difference.
The serious-event figures vary across the listed arms. For example, the registry reports 4 affected participants among 12 at risk in Arm A and 12 among 16 at risk in Arm J. Other listed examples include 23 among 52 at risk in Arm F and 25 among 38 at risk in Arm P. These are arm-specific counts as posted, not evidence of a statistically tested difference. The registry record does not report confidence intervals, hypothesis tests, or an adjustment for differences among arms. The data also do not provide a single comparative result for the primary composite outcome.
The other adverse-event counts are also listed by arm, but should not be read as a severity ranking or as proof that one regimen is safer than another. The record's summary outcome includes serious adverse events, adverse events leading to discontinuation, or death, while the posted arm-level data distinguish serious and other adverse-event categories. The relationship between each category and all components of the primary composite is not fully detailed in the record. Death counts are not reported in the posted group data.
Serious-event terms listed in the record include pneumonia, malignant neoplasm progression, and pneumonitis, each reported as 22.2%; pleural effusion at 15.4%; anaemia at 13.8%; and pyrexia at 13.3%. The denominator and the precise calculation basis for these term percentages are not reported in the registry record. They should therefore be read as registry-reported percentages, not recalculated as arm-level risks or compared across arms.
The enrollment figure describes the study overall, while the safety results are displayed for particular groups. It should not be treated as a denominator for each arm or as a replacement for arm-specific numbers at risk. Because this is a multi-arm Phase I safety study, these findings are most informative as descriptive safety observations within the reported groups. They do not establish comparative efficacy, and the record does not report a formal inferential analysis of the safety counts.
9. Statistical Methods Explained
The central statistical issue is the distinction between description and comparison. The registry reports counts of participants at risk and affected in several arm-level safety categories. A count is a direct description of the participants represented in that category. A comparison asks a further question: whether an observed difference between treatment groups is compatible with random variation, or whether it provides evidence of a treatment effect. The registry record does not report such a comparison for the primary outcome.
What does a participant count describe?
A participant count records how many people in a group met a defined event criterion during the relevant reporting period. The accompanying number at risk identifies the group denominator for that posted result. Counts can be useful for describing the experience in each arm, especially when the study is focused on safety. But a count does not show the precision of an estimated event risk by itself. For that, analysts commonly report an interval estimate, such as a confidence interval. In general, a confidence interval expresses a range of values compatible with the observed data under the method's assumptions. No confidence intervals for these safety findings are reported in the registry record.
Counts also depend on the outcome definition and the observation period. The primary outcome combines serious adverse events, adverse events leading to discontinuation, or death, with follow-up from first dose to 30 days after the last dose. The available group-level fields separately report serious and other adverse-event figures, and the death entries are null. The record does not provide a full component-by-component primary outcome result for every arm. These distinctions matter: one should not assume that a count in a particular adverse-event category is equivalent to the full composite endpoint.
Why is a direct arm comparison difficult?
General statistical principle: comparing two event counts requires attention to the denominators, uncertainty, group assignment, outcome definitions, and analysis plan. Random assignment can support a fair comparison when the trial's design and analysis preserve that assignment and when the comparison was planned and appropriately conducted. It does not make every pair of arms automatically comparable. This study includes different drug combinations, histology groups, maintenance settings, and other clinical subgroups. Some comparisons may address distinct clinical questions, and the registry record does not specify a single common comparator or planned pairwise contrasts.
It is also important to distinguish an observed difference from evidence that a difference is unlikely to arise by chance. In general, inferential analyses use a specified statistical model and report estimates with uncertainty, often alongside a test result. The registry record lists no analyses and does not report a model, confidence intervals, p-values, or a statistical analysis plan. No significance claim can be drawn from the counts alone. A recalculated comparison would require assumptions and could not replace the sponsor's own analysis; no recalculated comparison is reported in the registry record.
How should the sample-size illustration be understood?
The study's sample-size illustration is described as a planning exercise based on an observed effect, not as the trial's own design justification. Its assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events, while other outcomes use participants per arm. These are planning assumptions, not observed trial findings, and they do not establish that the trial was designed or powered according to those assumptions.
In general, a sample-size calculation estimates the information needed to detect a chosen effect under specified assumptions. It depends on the event rate or variability, the effect considered meaningful, the allocation plan, and the analysis method. A planning illustration based on an observed effect is not observed power. Observed power, calculated after looking at results, does not provide a substitute for confidence intervals or a planned analysis. The registry record does not report the original sample-size justification or the assumptions used to plan enrollment.
What does the study's phase contribute to interpretation?
Phase I identifies the study as an early-phase investigation, and the registry summary explicitly emphasizes safety and tolerability across regimens. In general, early-phase studies can generate safety descriptions and inform later research, but a descriptive safety pattern is not a definitive comparative assessment. The broad range of regimens and populations also means that the purpose and interpretation of an arm's result should be tied to that arm's treatment and eligibility context. The posted information does not provide a common effect estimate that combines the arms, nor does it establish a single treatment ranking.
The registry lists objective response rate and progression-free survival rate at Week 24 as secondary outcomes. Those endpoints would require their own definitions, denominators, follow-up handling, and analysis methods. The registry record does not report those details or their results in the information. Accordingly, the statistical interpretation should stay with the descriptive safety counts and the limits of the registry reporting, rather than extending to unreported efficacy analyses.
10. Multiplicity, Missing Data and Analysis Populations
The study evaluates many regimens and lists multiple outcome types: a primary safety outcome, objective response rate, and progression-free survival rate at Week 24. When several outcomes or treatment comparisons are tested, the chance of at least one apparently unusual result can increase. In general, a prespecified multiplicity strategy can address that issue by defining which comparisons are primary and how error rates are controlled or interpreted. The registry record does not report a multiplicity plan, planned pairwise comparisons, or a hierarchy among the secondary outcomes.
The record lists randomized allocation but does not report the analysis population used for any comparative analysis. The primary outcome description specifies all treated participants as its population. It does not state whether analyses of other outcomes used an intention-to-treat population, a per-protocol population, or another defined group. These details are important because the populations included in an analysis can affect its interpretation.
Missing-data methods are not reported in the registry record. The endpoint timeframe and the primary population are stated, but the registry does not explain how incomplete follow-up, missing event information, or treatment discontinuation was handled in an analysis. The group data include null death entries; death results are therefore not reported in those entries. A null entry should not be interpreted as a count of zero.
The registry record also does not report interim analyses, stopping rules, or a complete statistical analysis plan. Without those details, readers cannot assess whether the displayed analyses follow prespecified rules or how uncertainty and multiplicity were addressed. The available information supports descriptive reading of the posted group counts, not reconstruction of a complete confirmatory analysis.
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 |
|---|---|---|---|
| Arm A: Nivolumab + Gemcitabine + Cisplatin | 4 | 12 | 33.3% |
| Arm J: Nivolumab + Ipilimumab | 12 | 16 | 75.0% |
| Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) | 3 | 13 | 23.1% |
| Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) | 4 | 13 | 30.8% |
| Arm M: Nivolumab | 4 | 12 | 33.3% |
| Arm N: Nivolumab + Ipilimumab | 12 | 31 | 38.7% |
| Arm O: Nivolumab + Ipilimumab | 21 | 40 | 52.5% |
| Arm P: Nivolumab + Ipilimumab | 25 | 38 | 65.8% |
| Arm Q: Nivolumab + Ipilimumab | 25 | 39 | 64.1% |
| Arm B: Nivolumab + Pemetrexed + Cisplatin | 10 | 15 | 66.7% |
| Arm C: Nivolumab + Paclitaxel + Carboplatin | 17 | 29 | 58.6% |
| Arm D: Nivolumab + Bevacizumab Maintenance | 3 | 12 | 25.0% |
| Arm E: Nivolumab + Erlotinib | 11 | 21 | 52.4% |
| Arm F: Nivolumab | 23 | 52 | 44.2% |
| Arm G: Nivolumab + Ipilimumab | 6 | 9 | 66.7% |
| Arm H: Nivolumab + Ipilimumab | 12 | 15 | 80.0% |
| Arm I: Nivolumab + Ipilimumab | 5 | 9 | 55.6% |
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 |
|---|---|
| Arm A: Nivolumab + Gemcitabine + Cisplatin | 12 of 12 |
| Arm J: Nivolumab + Ipilimumab | 16 of 16 |
| Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) | 11 of 13 |
| Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) | 13 of 13 |
| Arm M: Nivolumab | 11 of 12 |
| Arm N: Nivolumab + Ipilimumab | 30 of 31 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: Nivolumab + Gemcitabine + Cisplatin | Arm J: Nivolumab + Ipilimumab | Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) | Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) | Arm M: Nivolumab | Arm N: Nivolumab + Ipilimumab |
|---|---|---|---|---|---|---|---|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 2 of 12 | 1 of 16 | 0 of 13 | 2 of 13 | 0 of 12 | 2 of 31 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 2 of 16 | 0 of 13 | 2 of 13 | 0 of 12 | 2 of 31 |
| Pneumonia | Infections and infestations | 1 of 12 | 1 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 3 of 31 |
| Adrenal insufficiency | Endocrine disorders | 0 of 12 | 1 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 2 of 31 |
| Hypophysitis | Endocrine disorders | 0 of 12 | 0 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 2 of 31 |
| Colitis | Gastrointestinal disorders | 0 of 12 | 2 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 0 of 31 |
| Diarrhoea | Gastrointestinal disorders | 1 of 12 | 0 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 1 of 31 |
| Disease progression | General disorders | 0 of 12 | 0 of 16 | 0 of 13 | 0 of 13 | 1 of 12 | 1 of 31 |
| Fatigue | General disorders | 0 of 12 | 2 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 0 of 31 |
| Lung infection | Infections and infestations | 0 of 12 | 2 of 16 | 0 of 13 | 0 of 13 | 0 of 12 | 0 of 31 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Nivolumab + Gemcitabine + Cisplatin | Arm J: Nivolumab + Ipilimumab | Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) | Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) | Arm M: Nivolumab | Arm N: Nivolumab + Ipilimumab |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 10 of 12 | 11 of 16 | 6 of 13 | 7 of 13 | 7 of 12 | 16 of 31 |
| Cough | Respiratory, thoracic and mediastinal disorders | 6 of 12 | 6 of 16 | 3 of 13 | 8 of 13 | 5 of 12 | 11 of 31 |
| Nausea | Gastrointestinal disorders | 8 of 12 | 8 of 16 | 2 of 13 | 0 of 13 | 2 of 12 | 9 of 31 |
| Diarrhoea | Gastrointestinal disorders | 3 of 12 | 6 of 16 | 5 of 13 | 1 of 13 | 1 of 12 | 11 of 31 |
| Constipation | Gastrointestinal disorders | 10 of 12 | 6 of 16 | 0 of 13 | 1 of 13 | 3 of 12 | 6 of 31 |
| Decreased appetite | Metabolism and nutrition disorders | 8 of 12 | 8 of 16 | 1 of 13 | 3 of 13 | 2 of 12 | 4 of 31 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 12 | 6 of 16 | 3 of 13 | 1 of 13 | 1 of 12 | 11 of 31 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 12 | 3 of 16 | 1 of 13 | 2 of 13 | 0 of 12 | 13 of 31 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 12 | 3 of 16 | 1 of 13 | 1 of 13 | 2 of 12 | 9 of 31 |
| Anaemia | Blood and lymphatic system disorders | 8 of 12 | 1 of 16 | 1 of 13 | 0 of 13 | 0 of 12 | 4 of 31 |
Serious events with the highest arm-level rate: pneumonia (22.2%), malignant neoplasm progression (22.2%), pneumonitis (22.2%), pleural effusion (15.4%), anaemia (13.8%).
The registry gives serious-event and other adverse-event counts separately by listed group, with numbers at risk and affected. For example, Arm A has 4 serious-event-affected participants among 12 at risk, while Arm F has 23 among 52 at risk. These values are descriptive and should be read with the arm name and its treatment setting. They are not direct estimates of a treatment difference, and a larger count in one arm does not by itself imply a greater risk than in another arm.
The primary outcome title includes serious adverse events, adverse events leading to discontinuation, or death, but the posted group data do not show every component of that composite separately. Death entries are null, so death counts are not reported in those results. The record also does not provide confidence intervals or comparative tests for the group counts. The figures therefore do not quantify statistical uncertainty or establish a safety ranking.
The listed serious-event terms include pneumonia, malignant neoplasm progression, and pneumonitis at 22.2% each; pleural effusion at 15.4%; anaemia at 13.8%; and pyrexia at 13.3%. Their denominator and calculation basis are not reported in the registry record. The percentages should be treated as reported term summaries, not as comparable risks across treatment arms. In general, safety interpretation also depends on event definitions, observation time, and completeness of follow-up.
12. What the Result Does, and Does Not, Mean
The registry record describes a completed, randomized, unmasked, parallel Phase I study of nivolumab across multiple regimens and treatment settings for NSCLC. It reports an enrollment of 472, several arm-level safety counts, and a primary outcome focused on serious adverse events, adverse events leading to discontinuation, or death. The group counts show that participants in the listed arms experienced serious and other adverse events during the recorded study period. The listed serious-event terms and their percentages provide additional descriptive information, although their calculation basis is not stated.
These observations do not establish that nivolumab, a combination regimen, or a particular treatment strategy is effective or ineffective. They do not establish that one arm is safer than another, because the record does not report a formal comparison, uncertainty intervals, or a complete description of planned contrasts. The diverse regimens and populations make it especially important not to interpret arm-level differences as though they came from a single standardized comparison.
The primary outcome is a composite safety measure, but the posted group data do not fully report its components for every arm. Death counts are not reported in the group entries. The registry lists objective response rate and progression-free survival rate at Week 24 as secondary outcomes, but their results are not reported in the available record. Consequently, no conclusion about response, progression-free survival, or relative benefit can be drawn from these safety counts.
In general, an observed count is one part of an evidence assessment. Interpretation also depends on outcome definitions, denominators, follow-up, uncertainty, allocation and analysis methods, and the clinical question the comparison was designed to address. Several of those analysis details are not reported in the registry record. The appropriate reading is therefore descriptive: these are posted safety observations within specified study groups, not a complete comparative evaluation of treatment effects.
13. Why This Trial Matters Statistically
This study illustrates a recurring challenge in clinical-trial interpretation: a randomized label does not mean that every reported arm can be treated as part of one simple head-to-head comparison. The registry describes a parallel, unmasked Phase I study with varied chemotherapy combinations, immunotherapy combinations, monotherapy, and maintenance settings. The population also differs across arms, including histology-specific groups and participants with untreated asymptomatic brain metastases without cerebral edema. Statistical interpretation must keep those differences in view.
The study also shows why safety counts need context. The primary outcome combines serious adverse events, adverse events leading to discontinuation, or death, while the posted group results distinguish serious and other adverse-event counts. The death entries are null. Without a complete breakdown of the composite, it is not possible to infer how each component contributed to the primary outcome. Reported terms and percentages can describe the safety record, but without denominators and a stated calculation basis they should not be used to compare risks across arms.
Finally, this record highlights the difference between a planning illustration and an actual statistical analysis. A sample-size illustration based on an observed effect and stated assumptions does not establish the trial's original design rationale or observed power. The registry does not report a full analysis plan, multiplicity approach, missing-data methods, or inferential results. These absences limit what can be concluded from the posted data and underline the value of transparent reporting of endpoints, analysis populations, uncertainty, and prespecified comparisons.
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 registry record does not report a complete arm-by-arm result for the primary composite outcome. Although the primary outcome is defined as participants who experienced serious adverse events, adverse events leading to discontinuation, or death, the posted safety groups display serious and other adverse-event counts. Death entries are null, and the record does not explain the relationship between those separate group fields and every component of the composite.
There are no reported confidence intervals, p-values, or formal comparative analyses in the record. The registry lists no analyses, and does not describe the statistical model, planned comparisons, multiplicity control, interim analyses, or stopping rules. Missing-data handling and the analysis populations for secondary outcomes are also not reported. The primary outcome population is identified as all treated participants, but that does not specify the populations used for other outcomes.
The arms cover different regimens and clinical subgroups, which limits interpretation of simple between-arm contrasts. The registry identifies randomized allocation but does not report the allocation procedure or a common comparator. The posted percentages for serious-event terms lack a reported denominator and calculation basis. The record lists response rate and progression-free survival rate at Week 24 as secondary outcomes but does not provide their results in these data.
These limitations mean that the posted safety information is descriptive rather than a complete comparative assessment. Details not included in the registry record cannot be inferred from the group counts or treatment descriptions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012) — NCT01454102.
- Registry record last updated 2021-10-12; status last verified 2021-09.
- Results first posted 2019-08-05.
- 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
CheckMate 012 (NCT01454102) is recorded as a completed Phase I, randomized, unmasked, parallel study sponsored by Bristol-Myers Squibb. It evaluated nivolumab alone and in combinations across several treatment settings for stage IIIB/IV NSCLC. The registry lists enrollment of 472, a start date of 2011-12-16, and primary completion on 2016-07-20.
The primary outcome is the number of participants experiencing serious adverse events, adverse events leading to discontinuation, or death, from first dose to 30 days after the last dose. The primary outcome population is all treated participants. Secondary outcomes are objective response rate and progression-free survival rate at Week 24. Arm-level serious and other adverse-event counts are reported for listed groups; death entries are null. The registry record does not report a comparative analysis, confidence intervals, a statistical analysis plan, or secondary outcome results in the information.