APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma (NCT03502330), a non-randomized phase 1 study. The primary outcome is Safety and Tolerability Measured by Assessing Serious Adverse Events (SAEs)and Adverse Events (AEs).

2. Clinical Question

The study is a phase I/Ib investigation of a three-drug combination in advanced cancers. Its dose-escalation component enrolled participants with advanced solid tumors in cohorts using different APX005M dose levels and combinations. The stated aim of that component was to determine the recommended phase II dose of APX005M. The expansion component was to study the combination separately in melanoma, non-small cell lung cancer and renal cell carcinoma.

The central statistical question is descriptive: what safety events were recorded in each reported cohort? Without random allocation to a control treatment, the results cannot establish how event counts compare with an otherwise similar group receiving a different treatment or no study combination. Differences among cohorts also cannot be read as treatment effects because cohort composition and regimen differ, and the registry does not report a randomized comparison.

The registry lists objective response rate as a secondary outcome, but the posted record contains no analyses. Therefore, it does not provide a reported response estimate or a statistical comparison of response. The study’s title and objectives describe the clinical setting and purpose; they do not by themselves establish an efficacy result.

3. Trial Design

The record describes a phase I/Ib study with non-randomized allocation, no masking and a single-group model. It lists enrollment of 42 and status as completed. The study began on 2018-06-09, and primary completion is recorded as 2022-01-05. These registry entries describe the study’s administrative record; they do not supply an analysis plan or explain how the enrollment target was chosen.

The phase 1 dose-escalation portion was planned across six cohorts of patients with advanced solid tumors. The cohort regimens varied by whether nivolumab was included and by the APX005M dose. Cabiralizumab was part of the described regimens. The stated purpose was to identify the recommended phase II dose of APX005M. The record then describes phase 1b expansion cohorts for advanced melanoma, non-small cell lung cancer and renal cell carcinoma, using the estimated recommended dose with nivolumab and cabiralizumab.

The listed regimens specify treatment on 14-day cycles during dose escalation, and day 1 of each 14-day cycle for the expansion cohorts. These descriptions identify planned treatment schedules; the registry does not report participant-level adherence, dose modifications or duration of treatment.

Although the record labels the study single-group, it presents adverse-event summaries by cohort. Those cohorts are not randomized arms. Their different regimens and potentially different participants mean that observed differences in event counts cannot be treated as controlled comparisons. The registry record does not report a statistical plan for comparing cohorts, a sample-size justification, interim analyses or a detailed analysis population.

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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability Measured by Assessing Serious Adverse Events (SAEs)and Adverse Events (AEs), measured over From study enrollment up to 12 months..

The primary outcome is safety and tolerability assessed by counting participants with serious adverse events and adverse events. The registry gives the unit as participants and states that the assessment period runs from study enrollment up to 12 months. It says adverse events and serious adverse events will be examined using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

Participant counts are useful in an early-phase study because they describe how many people in a cohort experienced events during the stated observation period. They give a direct summary of event occurrence, but they do not describe the full timing, duration, recurrence or severity distribution of events. Those details are not reported in the registry record.

In general, safety monitoring is important in early-phase research because it helps characterize events observed while a regimen is being studied. A count does not by itself determine whether an event was caused by a study drug. Nor does it show how the count would compare with another treatment, since this study has no randomized control group.

The record separately lists objective response rate as a secondary outcome. It does not post an analysis of that outcome. Accordingly, the primary endpoint information available is the registry’s safety-event count data, not an estimate of antitumor response or a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information available in the registry is limited. It identifies the study as phase I, non-randomized, unmasked and single-group, and describes a dose-escalation stage followed by disease-specific expansion. It does not report a detailed statistical analysis plan. The explanations below distinguish general statistical principles from methods stated in the record.

What does a participant count describe?

For the primary safety outcome, the unit is participants. A count indicates how many participants in a cohort were recorded as having an event during the stated follow-up period. It is not a measure of the number of separate event episodes: one participant can experience more than one event, and a participant-level count does not reveal recurrence. The record’s adverse-event fields also distinguish serious adverse events from other adverse events.

As a general statistical principle, event counts are easiest to interpret when the population at risk and observation period are clearly defined. The registry gives the safety timeframe as enrollment up to 12 months and reports cohort-specific numbers at risk for the posted summaries. It does not give participant-level follow-up, censoring details or an explanation of missing safety observations. Those omissions limit assessment of how complete and comparable the observation periods were.

Why is this not a controlled comparison?

In a randomized trial, random assignment is used to make treatment groups comparable on average, supporting a causal interpretation of between-group differences under suitable assumptions. This study is explicitly non-randomized and single-group. Its cohorts differ by regimen and, in the expansion stage, by cancer type. Any difference in their observed safety counts may reflect cohort composition, dose, treatment combination or other factors; the posted record does not separate these explanations.

General statistical comparisons across such cohorts are vulnerable to confounding. A numerical contrast between cohorts would not be a randomized treatment effect. The registry record does not report an adjusted comparison or a model intended to account for differences among cohorts.

What do uncertainty measures usually add?

In general, a confidence interval expresses the range of estimates compatible with the observed data under a stated statistical model and its assumptions. It can convey precision more fully than a point estimate alone. No confidence intervals are reported for the posted safety counts, and the record gives no inferential analysis for them. The small cohort counts displayed in several groups also mean that individual observations can have substantial influence on a descriptive estimate; no additional precision estimate should be inferred without a reported method.

The record states that adverse events were assessed using NCI CTCAE version 4.03. In general, a standardized grading framework can make event classification more consistent, but the registry summary does not provide the grade distribution or detailed event-level records. It also does not state how relatedness to study treatment was assessed.

How should planning illustrations be read?

General sample-size calculations are planning tools, not summaries of what happened in a completed trial. The stated assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. The record describes these as planning calculations based on the observed effect, not as the trial’s own design. They must not be interpreted as observed power or as evidence that the study was designed to detect a particular clinical effect.

Those hypothetical assumptions do not change the actual design: the study was non-randomized and single-group, not an equal-allocation randomized comparison. The registry does not report the trial’s own sample-size justification. It also does not report an analysis that would supply an observed treatment effect for a reliable efficacy-based planning interpretation. Any planning illustration should therefore be separated from the posted cohort-level safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 17 outcome measures, including safety and tolerability as the primary outcome and objective response rate as a secondary outcome. It reports 0 analyses. No multiplicity procedure is reported in the registry record. In general, when a study examines multiple outcomes or repeated comparisons, the chance of at least one apparently unusual result can increase; methods for controlling or describing that issue depend on the prespecified analysis plan. The record does not state whether any such plan was used.

Missing-data handling is not reported in the registry record. The posted safety summaries include numbers at risk for cohorts 1 through 8, but no information about incomplete follow-up, participants excluded from a summary, or how missing event information was handled. Cohort 9 does not have a corresponding adverse-event summary in the posted results. The record also does not state whether all enrolled participants were included in each outcome analysis.

The analysis populations are not described. In general, an analysis population defines which participants contribute to a particular result, and different definitions can affect interpretation. Here, the registry gives no detailed population definition beyond the cohort summaries and the primary outcome’s participant unit. It does not report whether analyses used all enrolled participants, treated participants or another specified group.

Without a reported multiplicity strategy, missing-data approach or analysis-population definition, the posted record does not permit a full appraisal of the intended inferential framework. These absences do not alter the descriptive event counts, but they constrain claims about precision, completeness and statistical significance.

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: anemia (33.3%), abdominal pain (33.3%), skin infection (33.3%), cpk increased (33.3%), stroke (33.3%).

For serious adverse events, the registry reports both participants at risk and participants affected for each listed cohort. For example, cohort 1 records 1 affected participant among 3 at risk, while cohort 6 records 5 among 6. The other adverse-event summary records all participants at risk as affected in each of cohorts 1 through 8. These figures describe participants, not the total number of event episodes.

The reported safety groups are cohorts with different regimens, not randomized treatment arms. Their counts should not be compared as though treatment assignment were controlled. The registry also lists deaths in cohort 4 and cohort 7, but does not provide a causal relationship assessment in the posted summary. The record does not give adverse-event counts for cohort 9.

In general, a serious adverse event is a category distinct from an ordinary event count, and event classification does not by itself establish that treatment caused the event. The registry says the assessment used NCI CTCAE version 4.03, but does not post severity grades, event timing or treatment-relatedness assessments. The listed serious-event terms and percentages should be read as registry entries; their cohort-specific denominators are not reported alongside that listing.

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

The result means that the registry records serious and other adverse events among participants in the listed cohorts during the stated safety observation period. It also lists several serious-event terms and reports deaths in two cohorts. These are observations from a phase I/Ib study, not estimates from a randomized comparison. They provide a descriptive account of the posted safety information, with the caveat that cohort 9 has no adverse-event summary in the record.

The result does not establish that any listed event was caused by APX005M, nivolumab or cabiralizumab. The posted summary does not provide event-level causal assessments, timing or severity distributions. Nor does it show how these counts compare with a control group. The absence of randomization is especially important because the cohorts use different regimens and include different disease groups.

The record also does not report an objective response rate analysis, despite listing objective response rate as a secondary outcome. The safety counts therefore cannot be used as evidence of tumor response or comparative efficacy. The study’s purpose and title describe what it set out to evaluate, but they are not a substitute for posted outcome estimates.

In general, a completed study status does not ensure that every planned result or analysis is present in the registry. Readers can interpret the cohort-level counts as recorded, while recognizing that the record does not provide a complete statistical account of safety, missing data, analysis populations or efficacy. No treatment recommendation or conclusion about benefit follows from these descriptive data alone.

13. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the role and limits of early-phase, non-randomized evidence. Dose escalation can organize study regimens around a safety-focused objective, and the record states that the escalation stage aimed to determine a recommended phase II dose of APX005M. The later expansion stage was organized by cancer type. Such a design can describe events observed during development, but it does not provide the same comparative evidence as randomized allocation.

The record’s cohort structure also makes interpretation more demanding. Regimens vary in APX005M dose and in whether nivolumab is included; expansion cohorts represent distinct diseases. Safety counts from these groups are therefore not interchangeable measures of a single treatment condition. Their differences may have multiple explanations, and the registry does not report an analysis that separates them.

Another statistical lesson is the distinction between observed data and inferential evidence. Participant counts are concrete descriptions of recorded events, while confidence intervals, adjusted estimates and hypothesis tests would address uncertainty or comparisons under specified methods. The registry reports no analyses, so readers should not infer statistical significance or precision beyond the counts themselves.

Finally, the posted record demonstrates why outcome reporting matters. It lists objective response rate as a secondary outcome, but no analysis is posted; it also lacks an adverse-event summary for cohort 9 and does not describe missing-data or analysis-population methods. These gaps do not erase the available safety observations, but they narrow what can be concluded. Clear separation of descriptive safety findings from unsupported comparative or efficacy claims is central to sound statistical interpretation.

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 detailed statistical analysis plan, sample-size justification, interim analyses, missing-data method or analysis-population definitions. It lists 17 outcome measures and 0 analyses. Objective response rate is named as a secondary outcome, but no response estimate or inferential result is posted. These omissions prevent a full assessment of the planned and completed statistical analyses.

The design is non-randomized and single-group, with cohorts that vary in treatment regimen and disease setting. Consequently, the posted cohort counts cannot be interpreted as controlled comparisons or used to isolate the effect of an individual drug or dose. The registry does not provide adjusted comparisons that might address cohort differences.

The adverse-event summaries are incomplete across the planned cohorts: results are listed for cohorts 1 through 8, but no adverse-event figures are reported for cohort 9. The record also does not provide event timing, severity distributions, treatment-relatedness assessments or detailed causes for the deaths listed in cohort 4 and cohort 7. The serious-event term listing does not state cohort-specific denominators.

Finally, the stated safety period extends from enrollment up to 12 months, but the registry does not describe completeness of follow-up or handling of missing event data. These limitations mean that the posted counts should be treated as descriptive registry results, not as a complete basis for causal, comparative or efficacy conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma — NCT03502330.
• Registry record last updated 2024-07-03; status last verified 2024-06.
• Results first posted 2023-08-18.
• 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

The registry identifies NCT03502330 as a completed phase I/Ib, non-randomized, unmasked, single-group study sponsored by Yale University. Enrollment is listed as 42. The recorded study start is 2018-06-09, and primary completion is 2022-01-05.

The study evaluates APX005M with cabiralizumab and nivolumab in advanced melanoma, non-small cell lung cancer or renal cell carcinoma. Its primary outcome is safety and tolerability assessed through serious adverse events and adverse events from enrollment up to 12 months, using NCI CTCAE version 4.03. Objective response rate is listed as a secondary outcome.

The registry posts adverse-event counts for cohorts 1 through 8, but not cohort 9. It reports 17 outcome measures and 0 analyses. No randomized comparison, efficacy analysis or detailed statistical plan is posted in the registry record.