Study of BMS-986315 Alone and in Combination With Nivolumab or Cetuximab in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of BMS-986315 Alone and in Combination With Nivolumab or Cetuximab in Participants With Advanced Solid Tumors (NCT04349267), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events and Deaths.

2. Clinical Question

This is principally a descriptive early-phase safety and evaluation question, rather than a randomized estimate of comparative treatment effect. The posted safety counts describe the participants in the listed groups; they do not establish that differences between groups were caused by dose or by the addition of another therapy. The registry record does not report a detailed primary statistical hypothesis, a comparative efficacy question, or the statistical procedures used to analyze the secondary outcomes.

3. Trial Design

The study is titled as a Phase 1/2 investigation of BMS-986315 as monotherapy and in combination with nivolumab or cetuximab in participants with advanced solid tumors. The registry lists both PHASE1 and PHASE2. Bristol-Myers Squibb is identified as the sponsor. The recorded start date is 2020-07-14, primary completion is 2024-08-22, and status is completed. Enrollment is 44.

The design is described as non-randomized, unmasked, and parallel. These characteristics matter when interpreting group outcomes. Non-randomized allocation means that the registry does not document random assignment to treatment groups; unmasked means no masking is recorded. In a parallel design, participants are assigned to a group and followed within that group rather than crossing between groups, but the detailed implementation is not reported. The record does not give the allocation procedures, dose-escalation rules, treatment schedules, or criteria for entering the different parts or groups.

The posted adverse-event breakdown identifies seven groups: four BMS-986315 monotherapy dose groups and three BMS-986315-plus-nivolumab groups. It gives group-level counts for serious adverse events, other adverse events, and deaths. Although cetuximab appears as an intervention and combination in the study description, no cetuximab group appears in that breakdown. Whether participants received that combination, and any corresponding group-level outcomes, are not reported in the registry record.

Eleven outcome measures are listed. In addition to the primary safety outcome, the secondary outcomes include objective response rate, duration of response, progression-free survival rate, and measures of BMS-986315 plasma concentration over time. The record lists no analysis entries. It does not report a detailed protocol, statistical analysis plan, sample-size justification, interim-analysis plan, or results for the listed secondary outcomes. The posted design therefore supports a description of the recorded study structure and safety counts, but not reconstruction of the full operational or statistical plan.

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: No participants were enrolled in Part 1C.

Only the first 6 of 7 groups are shown.

Overall Study

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events and Deaths, measured over From first dose (Day 1) and 100 days after last dose of study therapy (up to approximately 25 months).

The primary outcome is the number of participants with adverse events and deaths. It is a participant-count outcome: it concerns whether participants experienced events during the defined observation period, rather than the total number of event episodes or an event rate per unit of follow-up. The population is all treated participants. The timeframe begins at first dose on Day 1 and extends to 100 days after the last dose of study therapy, up to approximately 25 months.

The registry defines an adverse event as a new untoward medical occurrence or worsening of a pre-existing condition after signing informed consent, whether or not it is considered related to the study intervention. This can include an unfavorable sign, symptom, or disease temporally associated with study participation. A serious adverse event is defined by specified consequences, including death, a life-threatening event, or inpatient hospitalization or prolonged hospitalization. The posted group breakdown separates participants with serious adverse events from participants with other adverse events and also lists deaths.

Safety is a relevant outcome in an early-phase study evaluating an intervention alone and in combinations: a count can describe how many treated participants experienced events during the stated period. The count does not by itself measure event severity beyond the separate serious-event classification, establish causality, or show how risk compares with an equivalent untreated or randomized control group. The registry does not report additional endpoint rules, such as how repeated events were handled, how deaths were classified relative to adverse events, or the statistical analysis used for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a count of participants with adverse events and deaths as the primary outcome. A count is a direct description of how many participants in a defined group meet an outcome definition. It differs from a rate, which relates events to time at risk, and from a time-to-event analysis, which uses the timing of events and censoring. The posted outcome is framed as participants with events; the record does not report a time-to-event analysis for this primary outcome. General statistical interpretation should therefore begin with the group size and the event definition, not with a claim about event timing or comparative hazard.

What does a participant count tell the reader?

A participant count can communicate the observed burden in a group, provided the denominator and observation period are understood. The registry supplies groups at risk and counts of participants affected by serious adverse events and other adverse events, as well as deaths. Because the counts are small, each participant represents a meaningful part of a group’s observed experience. Small groups also make estimates imprecise: a count may change substantially in relative terms if only a small number of participants have a different outcome. This is a general property of sparse data, not a separate result for this study.

The count does not say how many separate episodes occurred in each participant. Nor does it reveal when an event began, how long it lasted, whether it recurred, or whether it led to a dose change. Those details are not reported in the registry record. The definitions also matter: adverse events include occurrences regardless of assessed relationship to treatment, while serious adverse events are classified by specified consequences. A reader should not assume that the categories are mutually exclusive across participants or that death counts are a subset of, or separate from, the event counts unless the record explicitly explains this.

Why does the design affect comparisons?

Random assignment is one method for creating groups that are comparable on average at the start of a trial. This study is recorded as non-randomized, so the posted groups cannot automatically be treated as balanced comparison groups. Differences in the safety counts may reflect who received each regimen, how they were selected, or other differences, in addition to any treatment-related effects. The record does not describe an adjustment strategy that would address such differences. General statistical comparisons between non-randomized groups require careful attention to confounding and selection; the registry record does not document methods for doing so.

The unmasked design also means that masking is not recorded. Masking can reduce some forms of influence on event reporting or assessment, although it cannot remove every source of bias. The registry does not say whether event adjudication was independent, whether definitions were applied centrally, or whether assessors were otherwise protected from knowledge of treatment. Such procedures should not be presumed.

What does the planning illustration represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are based on a stated fraction of the observed effect. They are planning calculations, not estimates of the trial’s actual design requirements, and not observed power. For time-to-event outcomes, the stated approach uses a total number of events; for other outcomes, it expresses a number of participants per arm. These are general planning conventions as described for the illustrations. The registry does not report that these assumptions were the study’s own design choices, and a planning calculation cannot repair the lack of randomization or turn a descriptive count into a causal comparison.

In general, a sample-size calculation depends on the outcome, the effect size to be detected, the significance level, allocation, and the assumed statistical model. Changing any of these assumptions changes the planning result. A calculation based on an observed effect can be especially dependent on the precision and variability of that observed estimate. The registry does not report a sample-size justification or the assumptions used by the sponsor when planning the trial. The stated illustration assumptions should therefore not be described as the trial protocol or as proof that the study had adequate power.

How should uncertainty be understood?

A confidence interval is, in general, a range of values compatible with the observed data under a specified statistical method. Its width communicates precision, while its interpretation depends on the model and the sampling assumptions. The registry record does not report confidence intervals for the primary safety counts. Without intervals or a prespecified analysis, the posted counts alone do not quantify uncertainty in a comparative effect. In small groups, apparent differences can be unstable, and an absence of a reported analysis is not evidence that groups are equivalent.

Over-dispersion is a general concern when count data vary more than a simple probability model assumes. It can lead to underestimated uncertainty if the model does not accommodate that variation. The registry does not report a model for count outcomes, a dispersion assessment, or a variance adjustment. That issue is relevant as a general methods consideration, but there is no basis to say over-dispersion was present or that a particular model was used in this study.

What can be inferred from the analysis record?

The registry lists no analysis entries. It also does not report the sponsor’s detailed statistical analysis plan, analysis populations beyond identifying all treated participants for the primary outcome, handling of missing outcomes, or methods for multiplicity. These omissions limit independent assessment of how the posted outcomes were selected and analyzed. General statistical principles can explain why those details matter, but they cannot substitute for the study-specific plan. The safest reading is to distinguish recorded outcome definitions and descriptive counts from unreported inferential analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary count of participants with adverse events and deaths and secondary outcomes for objective response rate, duration of response, progression-free survival rate, and BMS-986315 pharmacokinetics. When a study assesses multiple outcomes, the chance of at least one apparently notable result can increase if many statistical tests are conducted. General approaches to this issue include defining a primary outcome in advance, controlling an overall error rate, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, testing hierarchy, or adjustment method.

The record lists 0 analysis entries. It does not provide statistical tests or results for the secondary outcomes, and it does not report confidence intervals or a detailed analysis plan for the primary outcome. Thus, there is no basis to infer which outcomes were formally tested, whether tests were adjusted, or whether analyses were prespecified. Listing an outcome measure is not the same as reporting an analysis of that measure.

Information about missing outcome data is also not reported in the registry record. The record does not describe how incomplete follow-up, withdrawal, or missing assessments were handled, or whether the number analyzed differed from the number treated. The primary outcome identifies all treated participants as its population, but the number treated and any outcome-specific analysis population are not stated. These details affect how complete and representative an outcome count may be.

The record also does not report a protocol-based sample-size justification, interim-analysis plan, or detailed statistical analysis plan. Their absence from the registry record should not be filled by assumptions about common practice. Without those materials, readers cannot determine the intended inferential framework, the sponsor’s rules for interpreting secondary outcomes, or the planned response to missing data and multiple outcomes.

11. 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 (50.0%), pancreatic neoplasm (50.0%), tumour pain (50.0%), supraventricular tachycardia (20.0%), pneumonia (20.0%).

The adverse-event breakdown reports, for each listed group, the number at risk, the number affected by serious adverse events, the number affected by other adverse events, and the number of deaths. For example, in the Part 1A BMS-986315-80 mg group, 2 participants were at risk, 0 were affected by a serious adverse event, 2 were affected by other adverse events, and 1 death was recorded. In the Part 1B BMS-986315-600 mg plus nivolumab 480 mg group, 14 participants were at risk, 8 were affected by serious adverse events, 14 by other adverse events, and 7 deaths were recorded. The other groups have their own posted counts; these figures are group descriptions, not randomized comparisons.

The registry defines adverse events broadly and includes events whether or not they were considered related to study intervention. The death counts therefore should not be read as treatment-related deaths unless a causal assessment says so; no such assessment is reported in the registry record. The serious-event terms are accompanied by percentages, but their denominator and calculation context are not reported. Nor does the record explain whether a participant could contribute to multiple event categories. These counts and terms describe the posted safety record, but do not establish causation or comparative safety.

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

The record establishes that the study evaluated BMS-986315 alone and in combinations in participants with advanced solid tumors and that it recorded adverse-event and death counts for seven listed groups. It gives the outcome timeframe, describes how adverse and serious adverse events are defined, and lists secondary efficacy and pharmacokinetic measures. These registry entries support a description of what the registry records as the study’s purpose, design, and posted safety outcomes.

The record does not establish whether BMS-986315, nivolumab, or cetuximab produced a particular clinical benefit. Although objective response rate, duration of response, and progression-free survival rate are listed, their results are not reported in the registry record. The count data do not provide a randomized comparison, and there is no reported analysis that estimates a treatment effect. This absence should not be interpreted as evidence of no effect or as evidence that two regimens are equivalent.

The safety counts also do not establish that an event was caused by a study intervention. The adverse-event definition includes occurrences whether or not they were considered related, and the record does not provide causal assessments for the posted counts. Differences among the non-randomized groups cannot be attributed to dose or combination treatment from these data alone. The record also does not provide enough information to determine how representative the groups are of other participants with advanced solid tumors.

Precision is limited by the small group counts and by the absence of reported confidence intervals or inferential analyses. Counts describe what was recorded in the groups; they do not alone quantify the uncertainty around a broader risk or comparative effect. The secondary pharmacokinetic measures are named, but their numerical results are not reported in the registry record. Overall, the posted information is useful for understanding the study structure and the recorded safety experience, while leaving efficacy, causation, and comparative conclusions unresolved.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between an early-phase, non-randomized evaluation and a randomized comparison designed to estimate a treatment contrast. The study includes monotherapy and combination groups, but the registry does not record random assignment. Consequently, group-level counts can describe observed experiences but cannot by themselves isolate the effect of a particular dose or combination. Recognizing that distinction prevents descriptive safety summaries from being mistaken for controlled comparative evidence.

The registry also makes the outcome structure important to interpretation. The primary outcome is a count of participants with adverse events and deaths over a defined follow-up window, whereas the listed secondary outcomes include response, progression-free survival, and pharmacokinetic measures. Those outcomes answer different questions and require outcome-specific methods. The registry record lists no analysis entries, so the presence of outcome definitions should not be confused with published estimates or completed statistical tests.

The small sizes of the listed safety groups show why raw counts require context. A count is directly interpretable for the participants observed, but precision and generalizability are different questions. Confidence intervals, analysis methods, missing-data handling, and a clear denominator for the listed serious-event percentages would help readers assess uncertainty; these are not reported in the registry record. The record’s absence of a detailed analysis plan also means readers cannot evaluate any prespecified multiplicity strategy or inferential priorities.

Finally, the planning illustrations distinguish hypothetical design calculations from what the trial actually did. Their stated assumptions do not constitute a sample-size justification for this study, and they are not observed power. This distinction matters whenever planning calculations are based on an observed effect. The registry supports a careful statistical description of the trial’s structure and recorded counts, but not a broader claim about efficacy or comparative safety.

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 recorded design is non-randomized and unmasked, limiting interpretation of between-group differences. The registry does not report how participants entered dose or combination groups, what characteristics guided allocation, or whether groups were comparable at baseline. No adjustment strategy for potential differences between groups is reported. As a result, group contrasts should remain descriptive rather than causal.

The posted adverse-event breakdown includes monotherapy and nivolumab combination groups but no cetuximab group. Although cetuximab is named as an intervention, corresponding group outcomes are not reported in this breakdown. The registry record does not clarify whether participants received that combination or explain the scope of the posted groups relative to the full study.

The group sizes at risk are limited, and the record does not report confidence intervals for the safety counts. Small groups provide limited precision and may not represent broader populations. The record also does not explain whether the event categories overlap, how recurrent events were handled, or how the death counts relate to adverse-event classifications. Serious-event term percentages are listed without a reported denominator or calculation context.

For efficacy, the registry lists response and progression-related outcomes but reports no analysis entries or outcome results. It also does not report detailed eligibility criteria, treatment schedules, the allocation process, a statistical analysis plan, sample-size justification, interim analyses, missing-data procedures, or multiplicity handling. These limitations prevent reconstruction of the full protocol and constrain independent assessment of the study’s efficacy and inferential claims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of BMS-986315 Alone and in Combination With Nivolumab or Cetuximab in Participants With Advanced Solid Tumors — NCT04349267.
• Registry record last updated 2025-12-17; status last verified 2025-12.
• Results first posted 2025-12-17.
• 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.

18. Record Summary

NCT04349267 is a completed Phase 1/2, non-randomized, unmasked, parallel study sponsored by Bristol-Myers Squibb. It evaluated BMS-986315 alone and with nivolumab or cetuximab in participants with advanced solid tumors. The registry records enrollment of 44, a start date of 2020-07-14, and primary completion on 2024-08-22.

The primary outcome counts participants with adverse events and deaths among all treated participants, from first dose through 100 days after the last dose, up to approximately 25 months. The posted adverse-event breakdown covers four BMS-986315 monotherapy groups and three BMS-986315-plus-nivolumab groups. Cetuximab is listed as an intervention, but corresponding group-level safety outcomes are not reported in that breakdown.

Eleven outcome measures are listed, including safety, response, progression-free survival, and pharmacokinetic outcomes. The registry lists 0 analysis entries. Efficacy results and detailed statistical methods are not reported in the registry record, so the available information supports descriptive interpretation of the posted safety counts, not causal or comparative conclusions.