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 Nivolumab With or Without Ipilimumab or Chemotherapy in Treating Patients With Previously Untreated Stage I-IIIA Non-small Cell Lung Cancer (NCT03158129), a randomized phase 2 study. The primary outcome is Major Pathologic Response (mPR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03158129 |
| Phase | Phase 2 |
| Condition | Stage I Lung Non-Small Cell Cancer AJCC v7, Stage IA Lung Non-Small Cell Carcinoma AJCC v7, Stage IB Lung Non-Small Cell Carcinoma AJCC v7 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 101 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants had previously untreated stage I–IIIA non-small cell lung cancer considered amenable to surgical resection. The registry lists stage I, stage IA, stage IB, stage II, stage IIA, stage IIB and stage IIIA disease using AJCC v7 classifications. The primary outcome population is labeled intention-to-treat in the record.
Intervention
The study examined induction treatment involving nivolumab, either alone or alongside ipilimumab, chemotherapy, or both ipilimumab and chemotherapy. The chemotherapy drugs named in the registry include cisplatin, carboplatin, docetaxel and pemetrexed. The listed arm descriptions include four regimens, with some chemotherapy choices described as alternatives.
Comparator
Randomization assigned participants among the listed nivolumab-based regimens: nivolumab alone; nivolumab with ipilimumab; nivolumab with chemotherapy; or nivolumab with ipilimumab and chemotherapy. The brief summary mentions comparison with chemotherapy alone, but the listed arm descriptions do not include a chemotherapy-alone arm. The registry record does not report a primary-outcome comparison or its statistical results.
Primary question
The primary endpoint is major pathologic response, assessed from the lung resection specimen collected at surgery. The registry defines it using the average percentage of viable tumor cells across reviewed slides: tumors with at most 10% viable tumor cells meet the response definition. Participants who did not have surgery were classified as having no major pathologic response.
Statistically, the trial asks whether the randomized treatment strategies differ in the occurrence of this defined pathologic response in the stated population. The registry record identifies the endpoint and its classification rule, but does not report response counts, an effect estimate, uncertainty intervals, or a test of a treatment contrast. Therefore, the record describes the question and endpoint without giving a posted answer to the primary comparison.
3. Trial Design
This is a randomized, open-label, parallel-group phase II trial sponsored by M.D. Anderson Cancer Center. The registry records enrollment of 101 and describes four nivolumab-based treatment arms. Participants were assigned to nivolumab alone, nivolumab with ipilimumab, nivolumab with chemotherapy, or nivolumab with both ipilimumab and chemotherapy. Masking is listed as none, so treatment assignment was not masked according to the registry.
The intervention descriptions specify intravenous administration. Arm A describes nivolumab on days 1, 15, and 29. Arm B adds ipilimumab on day 1 to the nivolumab schedule described for Arm A. Arm C describes nivolumab and cisplatin on days 1, 22, and 43, with docetaxel or pemetrexed also named. Arm D describes ipilimumab, nivolumab, cisplatin or carboplatin, and docetaxel or pemetrexed. The arm descriptions state that treatment is given in the absence of disease progression or unacceptable toxicity. The available text for the chemotherapy-containing arm descriptions does not contain all of the schedule details.
The trial started on 2017-06-16, reached primary completion on 2024-11-13, and is listed as completed. The primary outcome is major pathologic response assessed using the lung resection specimen collected at surgery. Listed secondary outcomes include pathologic complete response, radiographic response, overall survival, event-free survival, residual tumor classification, postoperative complication, and mortality. The registry identifies 8 outcome measures, but does not report a primary-outcome analysis in the posted results.
Randomized parallel-group design supports comparisons among assigned strategies when the analysis and follow-up preserve the randomized groups. The registry record does not report allocation concealment, the randomization procedure, a detailed statistical analysis plan, or the planned contrasts among arms. Those details are not reported in the registry record, so the treatment descriptions alone do not establish which pairwise or combined comparisons were prespecified.
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: Fifty-three patients were enrolled in Arm A and Arm B, 9 of them were screen failures. Twenty-three patients were enrolled in Arm C, 1 of them was screen failure. Twenty-five patients were enrolled in Arm D, 3 of them were screen failures.
Overall Study
| Stage | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy |
|---|---|---|---|---|
| STARTED | 23 | 21 | 22 | 22 |
| COMPLETED | 21 | 16 | 22 | 20 |
| NOT COMPLETED | 2 | 5 | 0 | 2 |
Reasons for not completing this period:
| Reason | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy |
|---|---|---|---|---|
| Adverse Event | 0 | 1 | 0 | 0 |
| Death | 0 | 0 | 0 | 1 |
| High surgical risk | 1 | 1 | 0 | 0 |
| Progression | 1 | 1 | 0 | 0 |
| Lack of resectability | 0 | 1 | 0 | 0 |
| Declined surgery | 0 | 1 | 0 | 0 |
| No longer surgical candidate | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-treat popluation
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.
Population: Intention-to-treat population. Patients were enrolled in the study after giving consent. Age at enrollment was reported.
| Characteristic | Unit | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 23 | 21 | 22 | 22 | 88 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 11 | 8 | 10 | 13 | 42 |
| Age, Categorical: >=65 years | Participants | 12 | 13 | 12 | 9 | 46 |
| Age, Continuous | YEARS | 65.9 (46.5 to 83.6) | 66.2 (43.6 to 76.9) | 69.5 (45.6 to 79.3) | 63.1 (39.4 to 77.5) | 65.9 (39.4 to 83.6) |
| Sex: Female, Male: Female | Participants | 8 | 8 | 12 | 7 | 35 |
| Sex: Female, Male: Male | Participants | 15 | 13 | 10 | 15 | 53 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 3 | 1 | 6 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 3 | 0 | 3 | 7 |
| Race (NIH/OMB): White | Participants | 21 | 16 | 19 | 18 | 74 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 0 | 1 |
| Region of Enrollment: United States | participants | 23 | 21 | 22 | 22 | 88 |
| Smoking status: Never smoker | Participants | 5 | 3 | 5 | 5 | 18 |
| Smoking status: Former smoker | Participants | 14 | 12 | 17 | 13 | 56 |
| Smoking status: Current smoker | Participants | 4 | 6 | 0 | 4 | 14 |
| Stage: Stage IA | Participants | 4 | 4 | 0 | 0 | 8 |
| Stage: Stage IB | Participants | 7 | 8 | 1 | 0 | 16 |
| Stage: Stage IIA | Participants | 2 | 5 | 6 | 2 | 15 |
| Stage: Stage IIB | Participants | 5 | 0 | 4 | 7 | 16 |
| Stage: Stage IIIA | Participants | 5 | 4 | 11 | 13 | 33 |
| Histology: Adenocarcinoma | Participants | 13 | 13 | 16 | 13 | 55 |
| Histology: Adenosquamous carcinoma | Participants | 0 | 1 | 0 | 0 | 1 |
| Histology: Carcinoma with neuroendocrine features | Participants | 0 | 0 | 1 | 0 | 1 |
| Histology: Large cell carcinoma | Participants | 0 | 0 | 0 | 1 | 1 |
| Histology: Not otherwise specified NSCLC | Participants | 0 | 0 | 0 | 2 | 2 |
| Histology: Sarcomatoid carcinoma | Participants | 0 | 0 | 0 | 1 | 1 |
| Histology: Squamous cell carcinoma | Participants | 10 | 7 | 5 | 5 | 27 |
6. Primary Endpoint
The registry lists the primary outcome as Major Pathologic Response (mPR), measured over The lung resection specimen was collected at surgery..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is major pathologic response, a binary classification based on the amount of viable tumor in the lung resection specimen. The percentage of viable tumor cells is averaged across all reviewed tumor slides, with the specimen reviewed by two pathologists and their average score used. A tumor with at most 10% viable tumor cells is classified as having major pathologic response. Participants who did not undergo surgery are classified as having no major pathologic response.
This endpoint uses tissue collected at surgery to assess tumor response after induction treatment. A pathologic measure can capture changes in the resected tumor that are not conveyed solely by imaging. It also gives a clinically interpretable response category under the registry’s stated threshold. These are general reasons pathologic response measures may be used; they do not establish how well this endpoint predicts later outcomes in this trial.
The endpoint is recorded as a count of participants, while its defining rule refers to a percentage of viable tumor. Interpreting any treatment comparison would require the response count and the relevant denominator for each randomized group, together with an estimate of the between-group contrast and its uncertainty. Those primary-outcome results are not reported in the registry record. The record also does not report how disagreements between pathologists were handled beyond the stated use of the average score.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record provides a clear operational definition for major pathologic response but does not post the outcome data needed to estimate a treatment effect. There are no reported primary response counts, arm-specific response proportions, confidence intervals, or inferential test results in the posted results. Consequently, the record does not establish the magnitude or precision of differences among the randomized regimens on the primary endpoint.
The endpoint rule classifies tumors with at most 10% viable tumor cells as having major pathologic response and classifies participants without surgery as having no major pathologic response. This makes the classification rule explicit, but it does not reveal how many participants met it. Nor does the enrollment figure give the endpoint denominator in each arm: enrollment is not a substitute for outcome-specific counts or information about follow-up and evaluability.
The trial is randomized, which is intended to make treatment groups comparable on average at assignment. That design feature does not by itself supply an estimate of benefit, guarantee complete outcome ascertainment, or remove uncertainty from a result. Interpretation requires the actual outcome counts and a suitable analysis. Since those are not reported, no direction, size, or statistical certainty of a primary-outcome contrast can be stated from this record.
The registry lists secondary outcomes covering pathologic response, radiographic response, survival, residual tumor classification, postoperative complications, and mortality. The existence of outcome listings is not evidence that results were posted for each measure. The registry record lists 8 outcome measures, while the available results identify no analyses. Details such as estimates, uncertainty intervals, follow-up summaries, and handling of missing observations are not reported in the registry record.
Any planning illustration based on an observed effect must be distinguished from observed trial evidence. Such calculations describe the sample size that a hypothetical future study might require under stated assumptions; they are not the power achieved by this completed trial. Here, the primary comparison is not reduced to a single result, and an observed primary effect is not reported. Therefore, a planning illustration cannot be read as a substitute for the missing primary-outcome analysis or as proof that a treatment difference was detected.
In short, the posted record supports description of the design, treatment arms, response definition, and safety counts. It does not support a numerical conclusion about the primary endpoint. This is a limitation of what the registry record reports, not evidence that the trial found no difference.
9. Statistical Methods Explained
Statistical methods can only be described to the extent that the registry reports them. It identifies the design as randomized, unmasked, parallel-group, and phase II, and defines the primary endpoint. It does not report the primary analysis, effect measure, confidence interval method, hypothesis test, covariate adjustment, or analysis plan. Those methods are not reported in the registry record.
What does a binary endpoint mean?
As a general statistical explanation, a binary endpoint assigns each participant to one of two categories, such as meeting or not meeting a response definition. A group’s response proportion is based on the number meeting the definition relative to an appropriate denominator. A comparison between randomized groups can be expressed using a difference in proportions, a ratio, or another effect measure. Each answers the contrast in a different scale. The registry record does not report which effect measure was used for this endpoint, or any estimate on those scales.
For this trial, the endpoint definition specifies the response threshold and the handling of participants who did not have surgery. The rule therefore determines how those participants enter the endpoint classification. It does not provide the response counts or resolve how other unavailable measurements, incomplete specimens, or other missing outcomes were handled. Such missing-data procedures are not reported in the registry record.
Why do confidence intervals matter?
In general, a confidence interval describes the uncertainty around an estimated effect under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, but an interval must be interpreted alongside its estimate, outcome definition, and analysis population. A confidence interval is not a guarantee that the true effect lies within the displayed range. No primary-outcome interval is reported in the registry record, so the precision of any treatment contrast cannot be assessed.
A significance test, in general, evaluates how compatible the observed data are with a specified null hypothesis under the model used. A p-value alone does not describe the size or clinical importance of an effect. Because no primary test result or analysis specification is reported, there is no basis for characterizing the primary result as statistically significant or not statistically significant.
What does randomization contribute?
In general, random assignment helps balance prognostic characteristics across treatment groups on average and provides a basis for estimating causal effects of assignment, provided the analysis respects the design and outcome data are handled appropriately. Randomization does not ensure that groups have identical characteristics, especially in a phase II study, and does not replace reporting baseline information or outcome data. The record states that allocation was randomized but does not describe the randomization sequence, concealment, or stratification factors.
The trial is open-label, meaning masking is listed as none. Lack of masking can matter for outcomes influenced by assessment or decisions made with knowledge of treatment. The primary endpoint is based on pathologic review, and the registry says two pathologists reviewed the specimen and the average score was used. It does not report whether reviewers were blinded to treatment assignment, how disagreement was assessed, or whether the review process was standardized across arms. These details are not reported in the registry record.
How should planning calculations be read?
As a general principle, sample-size planning depends on the target effect, variability or event frequency, type I error, power, allocation, and analysis method. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. For time-to-event outcomes, the stated planning convention is a total number of events; for other outcomes, it is participants per arm. These are planning assumptions, not a description of the trial’s own design justification.
A planning sample size is an illustration of what a future study might require under the selected assumptions. It is not observed power, and it does not indicate whether the completed study succeeded in detecting an effect. Because the primary outcome is not reduced to one comparison in the registry record and its result is not reported, a planning calculation based on an observed primary effect cannot supply the missing trial estimate.
Binary outcomes can also be affected by sparse data, unequal group sizes, or different choices about the analysis population. General methods may use exact or approximate procedures, and adjusted or unadjusted models, depending on the design and data. The registry does not report which approach, if any, was used for the primary endpoint. No recalculated primary comparison can be presented from the posted registry results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and secondary outcomes that include pathologic complete response, radiographic response, overall survival, event-free survival, residual tumor classification, postoperative complications, and mortality. It identifies 8 outcome measures. Testing or estimating multiple outcomes can raise multiplicity concerns: when many hypotheses are examined, the chance of at least one apparently notable result can increase. As a general statistical approach, investigators may prespecify a hierarchy, adjust significance thresholds, or treat some outcomes as exploratory. The registry record does not report whether any such strategy was planned or used.
The primary outcome population is labeled intention-to-treat in the registry. In general, an intention-to-treat analysis retains participants in the groups to which they were randomized, regardless of treatment received, according to the specified analysis rules. The label alone does not describe the exact analysis set or how all deviations and unavailable outcomes were handled. The record’s explicit rule that participants without surgery count as having no major pathologic response is part of the endpoint definition; it is not a complete account of missing-data handling for every outcome.
Procedures for missing measurements, withdrawals, incomplete follow-up, or sensitivity analyses are not reported in the registry record. The record also does not report a statistical analysis plan, multiplicity adjustment, or interim-analysis procedure. These omissions prevent assessment of how outcome availability and multiple comparisons affected the reported inferential results; in this case, primary inferential results are not posted.
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 | 4 | 23 | 17.4% |
| Arm B - Nivolumab + Ipilimumab | 3 | 21 | 14.3% |
| Arm C - Nivolumab + Chemotherapy | 7 | 22 | 31.8% |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 3 | 22 | 13.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A - Nivolumab | 1 of 23 |
| Arm B - Nivolumab + Ipilimumab | 1 of 21 |
| Arm C - Nivolumab + Chemotherapy | 3 of 22 |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 3 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A - Nivolumab | 22 of 23 |
| Arm B - Nivolumab + Ipilimumab | 21 of 21 |
| Arm C - Nivolumab + Chemotherapy | 22 of 22 |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 22 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 23 | 0 of 21 | 3 of 22 | 1 of 22 |
| Lung infection | Infections and infestations | 0 of 23 | 0 of 21 | 2 of 22 | 1 of 22 |
| Diarrhea/Colitis | Gastrointestinal disorders | 1 of 23 | 1 of 21 | 0 of 22 | 0 of 22 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 1 of 23 | 1 of 21 | 0 of 22 | 0 of 22 |
| Sepsis | Infections and infestations | 0 of 23 | 0 of 21 | 2 of 22 | 0 of 22 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 23 | 0 of 21 | 0 of 22 | 0 of 22 |
| Thromboembolic event (pulmonary embolism) | Vascular disorders | 1 of 23 | 0 of 21 | 0 of 22 | 0 of 22 |
| Atypical Guillain-Barré syndrome | Nervous system disorders | 1 of 23 | 0 of 21 | 0 of 22 | 0 of 22 |
| Fall | Injury, poisoning and procedural complications | 0 of 23 | 1 of 21 | 0 of 22 | 0 of 22 |
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | 0 of 23 | 1 of 21 | 0 of 22 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy |
|---|---|---|---|---|---|
| Fatigue | Injury, poisoning and procedural complications | 8 of 23 | 8 of 21 | 16 of 22 | 8 of 22 |
| Nausea | Gastrointestinal disorders | 3 of 23 | 7 of 21 | 18 of 22 | 9 of 22 |
| Anemia | Blood and lymphatic system disorders | 7 of 23 | 4 of 21 | 12 of 22 | 11 of 22 |
| Diarrhea | Gastrointestinal disorders | 2 of 23 | 7 of 21 | 11 of 22 | 9 of 22 |
| Rash acneiform | Skin and subcutaneous tissue disorders | 6 of 23 | 13 of 21 | 6 of 22 | 0 of 22 |
| Creatinine increased | Investigations | 3 of 23 | 1 of 21 | 12 of 22 | 8 of 22 |
| Anorexia | Metabolism and nutrition disorders | 2 of 23 | 3 of 21 | 7 of 22 | 6 of 22 |
| Dizziness | Nervous system disorders | 1 of 23 | 3 of 21 | 8 of 22 | 4 of 22 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 23 | 2 of 21 | 2 of 22 | 9 of 22 |
| Hyponatremia | Metabolism and nutrition disorders | 5 of 23 | 2 of 21 | 6 of 22 | 1 of 22 |
Serious events with the highest arm-level rate: febrile neutropenia (13.6%), lung infection (9.1%), sepsis (9.1%), diarrhea/colitis (4.8%), pneumonitis (4.8%).
The registry separates serious adverse events from other adverse events and lists participants at risk and affected by group. In Arm A, 4 participants were affected by serious adverse events among 23 at risk, and 22 were affected by other adverse events among 23 at risk. In Arm B, the corresponding figures are 3 of 21 for serious events and 21 of 21 for other events. In Arm C, they are 7 of 22 for serious events and 22 of 22 for other events. In Arm D, they are 3 of 22 for serious events and 22 of 22 for other events.
The registry also lists deaths by arm: 1 in Arm A, 1 in Arm B, 3 in Arm C, and 3 in Arm D. These figures are presented as registry counts; the record does not establish that deaths were caused by treatment. The most frequently listed serious-event terms include febrile neutropenia at 13.6%, lung infection at 9.1%, sepsis at 9.1%, diarrhea/colitis at 4.8%, pneumonitis at 4.8%, and fall at 4.8%. The denominator and event-overlap details for these term percentages are not reported in the registry record.
These safety figures describe recorded events, not comparative causal effects. Differences in counts should not be treated as evidence of a treatment-related difference without an appropriate analysis and context about exposure, follow-up, and event definitions. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was a randomized phase II evaluation of nivolumab-based induction regimens in previously untreated stage I–IIIA non-small cell lung cancer considered amenable to surgical resection. It also establishes how the primary pathologic response category was defined, including the threshold of at most 10% viable tumor and the classification of participants without surgery as having no major pathologic response.
Those design and definition details are useful for understanding what the trial set out to study. They do not show how many participants experienced major pathologic response, whether response differed among arms, or how precise any estimated difference was. No primary-outcome analysis is reported in the registry record. The absence of a posted result cannot be interpreted as a finding of no effect, equivalence, or harm.
The listed safety counts and event terms describe reported adverse-event data, but they do not alone establish that a regimen caused an event or that safety differed between regimens. A fair comparison would require context about event definitions, observation periods, participant exposure, and an analysis accounting for the randomized design. These details are not reported in the registry record.
Secondary outcome listings likewise identify topics of interest rather than findings. Without posted estimates and their uncertainty, no conclusion about survival, radiographic response, postoperative outcomes, or other secondary measures can be drawn from the registry record. Statistical interpretation must distinguish a planned or defined outcome from a reported result: the former describes what was to be assessed, while the latter is needed to quantify what the observed data show.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of a randomized, parallel-group study with several active treatment strategies and a tissue-based endpoint. Its registry definition makes the response threshold explicit and specifies how participants without surgery enter the primary classification. Such details are essential because treatment comparisons depend on consistent outcome definitions and analysis populations.
The trial also illustrates why design information and results must be read separately. Randomization supports a comparative framework, but it does not tell readers the response frequency or the size and precision of an effect. The registry provides treatment descriptions and enrollment, yet the primary outcome analysis is not reported. A completed trial status does not itself establish that the results are available in this registry record.
There are multiple listed secondary outcomes, spanning response, survival, and postoperative measures. This makes transparency about the analysis plan and multiplicity especially relevant. Without those details, readers cannot determine which comparisons were prespecified, how uncertainty was assessed, or how multiple outcomes were handled. The record does not report these methods.
Finally, the safety listings demonstrate the importance of distinguishing event counts from comparative evidence. Counts can describe the reported experience in each arm, while causal interpretation requires more information and an analysis appropriate to follow-up and exposure. The registry record is therefore useful for understanding the study framework and endpoint definitions, but not for drawing a primary efficacy conclusion from the posted results.
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.
A central limitation of the registry record is that it does not report the primary major pathologic response counts or a statistical comparison. Without those data, the treatment effect and its precision cannot be assessed. The record also lists no analyses, so it does not supply inferential results for the primary endpoint or the listed secondary outcomes.
The available description does not report the planned contrasts among the four arms, the randomization procedure, allocation concealment, or a full statistical analysis plan. It also does not report whether pathologists were blinded to assignment or how reviewer disagreement was handled beyond the use of an average score. These omissions limit assessment of the analysis and outcome-measurement procedures.
Handling of missing outcomes other than the stated no-surgery rule is not reported in the registry record. Nor are sensitivity analyses, baseline characteristics, follow-up completeness, or the duration and detail of safety observation reported in the registry record for this account. The adverse-event term percentages are listed without denominator and overlap information, so they cannot be interpreted as participant-level comparative risks.
The chemotherapy-containing arm descriptions are incomplete in the available registry text, including parts of the schedules and alternative drug descriptions. The brief summary mentions chemotherapy alone as a comparator, while the listed arm descriptions specify four nivolumab-based arms and do not describe a chemotherapy-alone group. This difference in wording makes the intended comparison structure unclear from the record alone. These limitations concern what the registry record reports and should not be mistaken for evidence about unreported trial conduct or outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nivolumab With or Without Ipilimumab or Chemotherapy in Treating Patients With Previously Untreated Stage I-IIIA Non-small Cell Lung Cancer — NCT03158129.
- Registry record last updated 2026-04-06; status last verified 2026-03.
- Results first posted 2025-03-05.
- 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
NCT03158129 is a completed, randomized, open-label phase II parallel-group trial sponsored by M.D. Anderson Cancer Center. It enrolled 101 participants with previously untreated stage I–IIIA non-small cell lung cancer amenable to surgical resection. The listed arms evaluate nivolumab alone or in combinations with ipilimumab and chemotherapy.
The primary endpoint is major pathologic response in the lung resection specimen, defined by at most 10% viable tumor cells; participants without surgery are classified as having no major pathologic response. The registry also lists secondary response, survival, residual tumor, and postoperative outcomes. Although safety counts and serious-event terms are posted, the primary-outcome analysis and its statistical comparison are not reported in the registry record. The record does not report the multiplicity strategy, detailed missing-data procedures, or a complete statistical analysis plan.