A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer (NCT04702880), a randomized phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

This distinction matters when reading the results. The trial’s stated purpose includes both safety and progression-free survival, but the designated primary outcome in the posted results is the number of participants with adverse events. The time-to-event results for progression-free survival and overall survival provide additional comparisons, but the registry record does not report a p-value for either comparison. The registry record also does not report a statistical testing hierarchy or say how the safety and efficacy aims were ranked in the analysis.

The trial is randomized and compares two treatment regimens in parallel. Its results therefore describe the comparison between the assigned regimens in this trial, subject to the reported outcome definitions, populations, and analysis details. Randomization is a design feature, not a guarantee that estimates are precise or that every possible source of bias is absent. The open-label design means treatment assignment was not masked, a consideration when interpreting outcomes involving investigator assessment or the recording of adverse events.

3. Trial Design

This is a randomized, open-label phase 2 clinical trial with a parallel-group design. It enrolled participants with extensive-stage small cell lung cancer and compared two first-line regimens. Arm A received BMS-986012 with carboplatin, etoposide, and nivolumab; Arm B received carboplatin, etoposide, and nivolumab without BMS-986012. The registry record lists enrollment as 135. The reported primary safety population is all treated participants, with 66 participants in Arm A and 65 in Arm B for that outcome.

The study began on 2021-03-17, had a primary completion date of 2025-05-22, and is marked completed in the registry record. The primary adverse-event outcome was followed from first dose to 100 days after the last dose, or the primary cutoff date, whichever occurred first, with the timeframe described as up to approximately 43 months. The secondary time-to-event outcomes use follow-up described as up to approximately 56 months. These are stated outcome timeframes, not a report of the follow-up received by each participant.

The primary outcome is the number of treated participants with adverse events. Secondary outcomes include investigator-assessed progression-free survival, progression-free survival rates at specified time points, objective response rate, duration and time to response, overall survival, overall survival rates at specified time points, and anti-nivolumab antibody status. Numerical results are posted for investigator-assessed progression-free survival and overall survival among the secondary outcomes described in the record. The information reported for the other secondary outcomes does not include their numerical results.

The registry record does not report treatment doses, detailed eligibility criteria, the randomization procedure, or the planned statistical analysis method for these results. It also does not report how treatment adherence, treatment switching, or protocol deviations were handled. These omissions limit how specifically the design and analysis can be reconstructed from the record.

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.

Pre-treatment

Reasons for not completing this period:

Treatment - Induction Phase

Reasons for not completing this period:

Treatment - Maintenance Phase

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months).

The primary endpoint is the number of participants with adverse events among all treated participants. An adverse event is defined in the registry record as a new untoward medical occurrence or worsening of a pre-existing medical condition in a participant receiving study treatment; the event does not necessarily have to be caused by treatment. The recorded period begins with the first dose and ends 100 days after the last dose or at the primary cutoff date, whichever occurs first. The record describes the timeframe as up to approximately 43 months.

A count of participants with at least one adverse event is a participant-level safety measure: it records whether participants experienced an event during the defined period, rather than counting every event or measuring its duration. It is used to describe how frequently an event was recorded in each treatment group. Because the definition does not require a causal relationship, the count should not be read as the number of participants whose event was judged to have been caused by a study drug.

The posted results give 66 participants with adverse events in Arm A and 65 in Arm B, with the same respective counts at risk. This is a descriptive comparison of the recorded counts. The registry record does not report a statistical method or an inferential p-value for the primary endpoint. The endpoint’s broad definition also means it does not by itself distinguish event severity, seriousness, type, or attribution; those are separate considerations when reading the additional safety information.

7. Results Posted in the Registry

• Arm B: 100.0% (65/65) versus 100.0% (66/66) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Progression Free Survival (PFS) Per Investigator

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor; it was not recalculated.
• Result:
  • Arm A vs Arm B: hazard ratio 0.87 (95% CI 0.59–1.29) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Arm A vs Arm B and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor; it was not recalculated.
• Result:
  • Arm A vs Arm B: hazard ratio 0.80 (95% CI 0.54–1.18) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Arm A vs Arm B and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results include investigator-assessed progression-free survival and overall survival, both analyzed as time-to-event outcomes. Their median estimates are numerically higher in Arm A than Arm B, while the reported hazard ratios are below 1. At the same time, the 95% confidence intervals for both hazard ratios include 1 and extend to values above it. Taken together, the point estimates lean in one direction, but the uncertainty intervals do not pin down the size or direction of the underlying difference with precision.

These secondary outcomes connect to the study’s stated interest in progression-free survival and broader survival outcomes, but they are not the posted primary endpoint. The primary endpoint is the number of participants with adverse events. A favorable-looking numerical pattern in a secondary efficacy measure does not establish that the primary safety endpoint was met, nor does a safety count answer the efficacy question. Each endpoint addresses a distinct aspect of the comparison.

The registry lists additional secondary outcomes, including progression-free survival rates at specified time points, response measures, overall survival rates at specified time points, and anti-nivolumab antibody status. Numerical results for those outcomes are not reported in the registry record, so their direction and precision cannot be characterized from the information available. The presence of an outcome in a registry listing should not be treated as evidence of a particular result.

General statistical explanation: when many outcomes are examined, the chance of observing an apparently notable result by chance can increase. Methods that account for multiple comparisons, or a prespecified hierarchy for testing outcomes, can help control how confirmatory claims are made. The registry record does not report whether secondary outcomes were adjusted for multiplicity or whether they were intended as confirmatory or exploratory. Accordingly, unadjusted secondary findings generally carry less weight than a clearly prespecified primary analysis. Here, the absent p-values and unreported multiplicity approach further limit claims based on the secondary estimates.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Progression Free Survival Rate (PFSR) at 6 and 12 Months
• Progression Free Survival (PFS) Per Investigator
• Objective Response Rate (ORR)
• Duration of Response (DoR)
• Time to Response (TTR)
• Overall Survival (OS)
• Overall Survival Rate (OSR) at 12 and 24 Months
• Number of Participants With Anti-Nivolumab Antibody (ADA)

9. Statistical Interpretation

10. Statistical Methods Explained

Several different statistical summaries appear in the posted results, and each answers a different question. The primary safety result is a count of participants with adverse events. The secondary efficacy results are time-to-event summaries: medians and hazard ratios for progression-free survival and overall survival. These measures should not be conflated. A count describes how many participants met an event definition during a period; a median describes a time point in an estimated event-time distribution; a hazard ratio compares event rates over follow-up under a time-to-event analysis.

What does the adverse-event count represent?

The primary outcome counts participants with at least one adverse event, rather than counting the total number of adverse events. One participant can have more than one event, but a participant-level count does not reflect that additional event burden. Nor does the endpoint, by itself, describe seriousness, duration, severity, or whether an event was attributed to treatment. The registry definition explicitly includes occurrences that do not necessarily have a causal relationship with study treatment. The time window also matters: the record specifies follow-up from first dose to 100 days after the last dose or the primary cutoff date, whichever occurred first.

The posted primary comparison is a risk difference of 0.0 with limits of 0.0 and 0.0. A risk difference is generally the difference between the proportions experiencing the outcome in two groups. The record’s comparison shows no displayed difference, but it does not state the inferential method, confidence level, or p-value for this endpoint. The group counts and the risk-difference summary should therefore be interpreted as the registry reports them, without trying to infer a more detailed statistical procedure.

What do the medians and hazard ratios say?

For a time-to-event outcome, the median is the time by which half of the relevant estimated event-time distribution has experienced the event, under the analysis used. It is not the average time to the event, and it does not describe every participant’s experience. The posted medians for progression-free survival and overall survival are accompanied by 95% confidence intervals. These intervals communicate uncertainty around the median estimates, rather than a range containing a fixed proportion of individual participants’ event times.

A hazard ratio compares the event rate at a given time between groups, as represented by the analysis. A value of 1 corresponds to equal rates under that comparison; values below or above 1 indicate different estimated relative rates, with direction depending on which arm is the reference and how the event is defined. The record reports the hazard ratios as Arm A versus Arm B. It does not state the detailed model, adjustment variables, or method used to estimate them. The hazard ratio is not a ratio of the two medians, and it does not directly express a difference in median survival time.

For both time-to-event endpoints, the reported 95% confidence interval includes 1. In general, an interval that includes the null value is compatible with no group difference under the corresponding analysis, as well as with other values inside the interval. The width and placement of an interval help communicate how precisely an effect is estimated. The record reports no p-values for these comparisons, so it is not appropriate to supply or infer one from the intervals.

Why are time-to-event methods used?

General statistical explanation: time-to-event methods are useful when participants can have different lengths of follow-up or when some have not experienced the event by the time observation ends. They can use information about the time until an event while accounting for incomplete observation through censoring, provided the assumptions and censoring rules are suitable. The registry record does not describe the censoring rules, the handling of missing event times, or the specific estimation method for these outcomes. It identifies progression-free survival as time from randomization to documented tumor progression or death, whichever occurs first, and overall survival as time from randomization to death from any cause.

General statistical explanation: a confidence interval is an uncertainty summary for an estimate under a statistical procedure and its assumptions. A 95% confidence interval is not a statement that there is a 95% probability that a particular fixed effect lies inside the interval. It indicates the range of estimates compatible with the observed data at the stated confidence level under the method used. Because the method is not described in detail in the record, the intervals can be read at the reported level but not fully audited from the registry information alone.

How should the planning illustrations be read?

The planning illustrations use fractions of the observed effect and show target power levels. For the time-to-event outcomes, they report total events; for other outcomes, the record’s explanation says the illustrations are participants per arm. These are planning illustrations computed from observed effects under the stated assumptions, not the trial’s original design calculations and not observed power. A sample-size calculation asks what amount of information might be needed to detect a chosen effect under assumed conditions. It does not show that the trial actually had that power, nor does it change the uncertainty in the results already observed. The registry record does not report the trial’s own sample-size justification or original planning assumptions.

General statistical explanation: over-dispersion occurs when variability is greater than a statistical model expects. For count outcomes, ignoring over-dispersion can make uncertainty look smaller than it is. The primary endpoint is a count of participants with an event, rather than a count of all events per participant, and the registry record does not report an over-dispersion assessment or a model for this endpoint. It is therefore not possible to say whether such a method was considered or used.

11. Confidence Intervals and Precision

The time-to-event estimates are accompanied by 95% confidence intervals, which are the main reported indicators of statistical precision for these comparisons. For progression-free survival, the hazard ratio is 0.87, with an interval from 0.59 to 1.29. For overall survival, the hazard ratio is 0.80, with an interval from 0.54 to 1.18. Both intervals include 1, so the reported estimates are compatible with no relative difference as well as with values on either side of that reference. Their span cautions against treating either point estimate as a precise measure of the treatment contrast.

The median estimates also have uncertainty intervals. Progression-free survival medians are 6.47 months in Arm A, with an interval from 5.13 to 7.89 months, and 5.09 months in Arm B, with an interval from 4.76 to 6.67 months. Overall survival medians are 16.26 months in Arm A, with an interval from 12.22 to 23.66 months, and 13.08 months in Arm B, with an interval from 9.72 to 16.62 months. Overlap between intervals is not itself a formal test of the difference between groups; the reported hazard ratio is the direct comparative summary in the record.

Confidence intervals describe uncertainty under the analysis and assumptions used. Their interpretation is limited by the absence of detail on the time-to-event estimation method, censoring, and any adjustment variables. The registry record does not report p-values for the hazard-ratio analyses. The primary adverse-event comparison has limits of 0.0 and 0.0 alongside a risk difference of 0.0, but it does not report a confidence level or statistical method for that result. That display should not be mistaken for the same kind of precision summary as the 95% intervals for the secondary outcomes.

The arm sizes reported for the primary outcome are 66 and 65, while the secondary time-to-event summaries report 67 and 68. The registry record does not explain the difference in analysis counts or state the reasons for inclusion in each outcome analysis. Precision should therefore be understood in relation to the participants and analysis represented by each outcome, rather than assumed to be identical across endpoints.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary adverse-event endpoint and multiple secondary outcomes. It does not report a statistical testing hierarchy, a multiplicity adjustment, or whether the secondary outcomes were designated as confirmatory or exploratory. This matters because evaluating several outcomes can increase the chance of a result that appears notable by chance. Without a reported plan for controlling that issue, the secondary time-to-event estimates should be read as additional descriptive and inferential information rather than as a set of independently confirmed findings.

The record reports hazard ratios and 95% confidence intervals for investigator-assessed progression-free survival and overall survival, but no p-values for either comparison. It also does not report a p-value or confidence level for the primary adverse-event comparison. The absence of those details does not mean the analyses were not performed; it means the registry record does not report them. The method used for the hazard ratios and the method used for the primary risk-difference comparison are also not stated.

The analysis populations are not described in enough detail to reconstruct participant flow for each outcome. The primary endpoint is explicitly defined for all treated participants, with 66 and 65 at risk in the two arms. The secondary time-to-event outcomes report 67 and 68 participants by arm. The registry record does not explain why the analysis counts differ, how missing values were handled, whether any participants were excluded after randomization, or how participants without an observed event were treated in the time-to-event analyses.

The record also does not report whether any interim analyses were planned or conducted, how missing outcome data were addressed, or whether sensitivity analyses were performed. These elements can affect the interpretation of estimates and uncertainty, particularly when follow-up is incomplete or multiple analyses are considered. Their absence from the registry record should be treated as missing reporting, not as evidence that a particular method was or was not used.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant neoplasm progression (9.1%), febrile neutropenia (7.7%), pneumonia (6.2%), septic shock (4.6%), thrombocytopenia (3.1%).

The registry reports serious adverse events for 38 of 66 participants in Arm A and 34 of 65 in Arm B. It also reports other adverse events for 62 of 66 participants in Arm A and 62 of 65 in Arm B. These are participant counts within each group, not counts of every event. A participant may have experienced more than one event, and the summary does not describe the number, duration, or severity of all events.

The most frequently listed serious-event terms include malignant neoplasm progression at 9.1%, febrile neutropenia at 7.7%, and pneumonia at 6.2%; the record also lists septic shock at 4.6%, thrombocytopenia at 3.1%, and sepsis at 3.1%. Those percentages are reported as listed, and the record does not state the denominator for each term in the information. They should not be added together or interpreted as mutually exclusive categories.

Deaths are recorded for 50 participants in Arm A and 56 in Arm B. These counts are not, by themselves, evidence that deaths were caused by treatment; the record defines adverse events without requiring a causal relationship and gives no attribution details for these death counts. The safety summaries describe recorded events in the stated observation period, but they do not replace a fuller assessment of event timing, severity, attribution, exposure, or individual clinical circumstances.

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

The results describe what was recorded in a randomized comparison of BMS-986012 added to carboplatin, etoposide, and nivolumab versus the three-drug regimen alone. For the primary safety endpoint, the registry reports the same displayed participant-level event proportion in both arms and a risk difference of 0.0. Serious adverse-event and other adverse-event counts are also reported, along with deaths and selected serious-event terms. These observations summarize events in the defined populations and timeframes; they do not establish whether a particular event was caused by a treatment.

For the secondary time-to-event outcomes, the point estimates for progression-free survival and overall survival are numerically more favorable in Arm A, but the reported hazard-ratio confidence intervals include 1. The estimates therefore remain uncertain about the relative difference. The registry record does not report p-values for these comparisons or a formal conclusion against a prespecified criterion. These results should not be described as proof of benefit or proof of no difference.

The trial’s stated purpose includes acceptable safety and improved progression-free survival, but its posted primary endpoint is an adverse-event count and progression-free survival is secondary. The available results can inform how the reported endpoints compare, but the registry record does not report a complete analysis plan, multiplicity approach, detailed missing-data handling, or the results for every listed secondary outcome. Those omissions limit how far the findings can be interpreted.

The findings apply to the trial population, treatment regimens, outcome definitions, and follow-up represented in the record. They do not automatically generalize to different populations, treatment settings, or regimens. The completed status indicates the registry record marks the study complete; it does not itself resolve the uncertainty in the estimates or supply unreported analyses. Overall, the posted data offer a descriptive safety comparison and imprecise secondary time-to-event comparisons, rather than a definitive answer to every question raised by the study’s stated purpose.

15. Why This Trial Matters Statistically

This trial illustrates why a study’s stated purpose, designated primary endpoint, and secondary efficacy outcomes need to be separated when interpreting results. The registry describes an aim that includes safety and progression-free survival, yet the posted primary outcome is the number of participants with adverse events. Investigator-assessed progression-free survival and overall survival are secondary outcomes. A reader who treats all these endpoints as equivalent would miss an important distinction in the evidential role assigned to each.

It also demonstrates how estimates and uncertainty should be read together. The time-to-event point estimates favor Arm A numerically, but the confidence intervals include the null hazard ratio of 1 and cover a range of possible comparisons. The point estimates alone do not convey that uncertainty. Conversely, intervals including 1 are not proof that the regimens are identical; they indicate that the estimates do not precisely distinguish among the values inside the interval under the analysis.

The safety results highlight a separate interpretive issue: counts of participants with at least one event are not counts of all events and do not establish causation. Serious-event classifications, specific event terms, and deaths provide additional context, but each needs its own denominator, definition, and attribution information for a fuller assessment. The record’s broad adverse-event definition expressly does not require a causal relationship to treatment.

Finally, the missing reporting on statistical methods, multiplicity, analysis populations, and missing data is itself relevant. These details determine how confidently estimates can be interpreted and compared. A registry record can communicate useful outcome summaries while still leaving important analytical questions unanswered. This trial therefore offers a practical example of reading endpoint hierarchy, effect estimates, precision, and reporting limitations together rather than relying on any single number.

16. 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.

Several limitations specific to the information reported for this trial constrain interpretation. The study is open-label, and the progression-free survival outcome is assessed per investigator. The registry record does not describe safeguards against knowledge of treatment assignment influencing assessment, nor does it report independent review of progression. This does not establish that assessment was biased, but it leaves the assessment process unclear.

The primary adverse-event comparison is presented as a risk difference of 0.0 with limits of 0.0 and 0.0, without a reported method, confidence level, or p-value. The group counts are clear, but the registry information does not permit a full assessment of the inferential uncertainty for this primary comparison. The broad adverse-event definition also includes events that may not be treatment-related, and attribution information for the listed serious events and deaths is not reported.

The participant counts differ across the primary and secondary outcome summaries: the primary safety result reports 66 and 65, while the time-to-event summaries report 67 and 68. The registry record does not explain the difference in analysis populations. It also does not report censoring rules, missing-data procedures, detailed statistical methods, adjustment variables, or sensitivity analyses. The methods and interpretation of the hazard ratios therefore cannot be fully assessed from the record alone.

Only some of the listed secondary outcomes have numerical results in the information reported. The registry record also does not report a multiplicity strategy or a testing hierarchy, and it gives no p-values for the time-to-event comparisons. These limitations are about reporting and available analysis detail; they do not show that a particular unreported procedure was omitted or that a result is invalid. They do mean that conclusions should stay close to the posted estimates and their stated uncertainty.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer — NCT04702880.
• Registry record last updated 2026-06-17; status last verified 2026-05.
• Results first posted 2026-06-17.
• 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.

20. Record Summary

NCT04702880 is a completed, randomized, open-label phase 2 parallel-group trial in extensive-stage small cell lung cancer. It compared BMS-986012 with carboplatin, etoposide, and nivolumab against carboplatin, etoposide, and nivolumab alone. The registry lists enrollment as 135, a start date of 2021-03-17, and a primary completion date of 2025-05-22.

The posted primary outcome is the number of treated participants with adverse events. The results report 66 participants in Arm A and 65 in Arm B with adverse events, and a risk difference of 0.0. Secondary results include investigator-assessed progression-free survival and overall survival, with medians, hazard ratios, and 95% confidence intervals. Both reported hazard-ratio intervals include 1. The registry record does not report p-values for these comparisons or a detailed statistical analysis plan.

The record also provides serious adverse-event, other adverse-event, and death counts. Its reported information does not fully describe analysis populations, missing-data handling, or multiplicity procedures. These gaps are important context for interpreting the estimates and safety summaries.