A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer (NCT03026166), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose-limiting Toxicities (DLT).

2. Clinical Question

3. Trial Design

The registry describes NCT03026166 as a Phase 1/2 study of rovalpituzumab tesirine with nivolumab, with or without ipilimumab, for adults with extensive-stage small cell lung cancer. AbbVie is listed as the sponsor. Enrollment is reported as 42. The study began on 2017-03-30, and the primary completion date is 2019-07-03. Its status is listed as terminated.

The design is non-randomized and sequential, with no masking. The registry names a cohort receiving rovalpituzumab tesirine and nivolumab, and a second cohort receiving rovalpituzumab tesirine and nivolumab plus ipilimumab. The regimen descriptions for the latter include ipilimumab at 1 mg/kg and 3 mg/kg. The first regimen description includes maintenance therapy, but its text is truncated in the registry record, so the complete maintenance schedule is not reported there.

Because assignment was not randomized, the cohorts should not be interpreted as if one were a randomized control for the other. Sequential enrollment also means the registry’s design does not establish that the groups were comparable on measured or unmeasured characteristics. No matching, adjustment strategy, or formal between-cohort analysis is reported in the registry record.

The stated purpose was to assess safety and efficacy. The primary endpoint is the number of participants with dose-limiting toxicities during the period of up to 12 weeks. Listed secondary outcomes are objective response rate, duration of response, progression-free survival, and overall survival. Although the registry lists 6 outcome measures, it reports 0 analyses in the posted record. Outcome estimates, uncertainty intervals, and inferential test results are not reported in the registry 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.

Before assignment: Three study cohorts were planned to enroll approximately 30 participants in each, including a dose-limiting toxicity (DLT) evaluation phase (the first 12 weeks of any treatment for all participants) and an expansion phase. However, Cohort 2 was limited to 12 participants and Cohort 3 was not opened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT-evaluable participants were those who completed 4 cycles treatment during the DLT period or stopped treatment earlier due to DLT.

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 Dose-limiting Toxicities (DLT), measured over Up to 12 weeks.

The primary endpoint is the number of participants with dose-limiting toxicities, assessed for up to 12 weeks. A DLT is defined by specified severe blood-count abnormalities, a clinically significant laboratory abnormality, or a serious non-laboratory adverse event during the evaluation period. The registry uses grading according to NCI CTCAE version 4.03. Examples include qualifying grade 4 thrombocytopenia, grade 4 neutropenia, grade 4 anemia unrelated to underlying disease, and grade 3 or 4 non-laboratory adverse events, subject to the stated exceptions and duration or resolution criteria.

This endpoint is used in early-phase research to characterize treatment-related safety over a defined period and to identify toxicities that meet prespecified severity criteria. Counting participants with a DLT gives a direct measure of how many people in the evaluable group crossed that definition. It does not capture every possible adverse event: events that do not meet the DLT criteria are outside this endpoint, even if they matter clinically or appear in broader safety reporting.

The registry defines DLT-evaluable participants as those who completed 4 cycles of treatment during the DLT period or stopped earlier because of a DLT. This makes the endpoint’s interpretation dependent on the evaluable population, not simply enrollment. The number meeting the definition and the number of DLTs observed are not reported in the registry record, so the primary endpoint cannot be quantified from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a non-randomized sequential design imply?

In a randomized trial, chance assignment is used to make groups comparable, on average, with respect to measured and unmeasured characteristics. This study is listed as non-randomized and sequential, so that protection against systematic group differences is absent. The registry does not report a random allocation procedure or masking. A comparison between the listed regimens would consequently be observational in character, even though the interventions were studied within one trial record.

General statistical principle: a difference in observed outcomes between non-randomized cohorts may reflect both treatment and differences in who entered each cohort or when they were treated. Adjustment can address measured factors when suitable data and a prespecified method are available, but cannot guarantee removal of unmeasured confounding. No adjusted comparative analysis is reported in the registry record. The design therefore supports descriptive reading of each cohort, rather than a causal interpretation of differences between them.

What does the primary endpoint count?

The primary endpoint is a participant count: people meeting the registry’s DLT definition within the period of up to 12 weeks. The DLT criteria combine laboratory and clinical events with severity, duration, or resolution requirements. They are not a count of all adverse events or a measure of all possible treatment risks. The endpoint population is specifically defined as participants completing 4 cycles in the evaluation period or stopping earlier because of a DLT.

General statistical principle: a count is easiest to interpret alongside its relevant denominator and population definition. A count alone does not tell the reader how common the outcome was. The registry record does not report the primary endpoint count or the number of DLT-evaluable participants, so neither a rate nor its precision can be assessed from the posted primary results.

How should estimates and confidence intervals be understood?

General statistical principle: an estimate summarizes the observed data, while a confidence interval describes sampling uncertainty under a statistical model and analysis procedure. Wider intervals indicate less precision; narrower intervals indicate greater precision, assuming the model is appropriate. An interval does not account automatically for design limitations such as non-random allocation, missing outcome data, or selective reporting. No primary endpoint estimate or confidence interval is reported in the registry record.

For binary outcomes, a proportion can describe the share of an analysis population experiencing an event. Its interpretation depends on the event definition, the denominator, and how participants with unavailable information are handled. For time-to-event outcomes such as progression-free survival or overall survival, estimates also depend on event definitions, follow-up, censoring rules, and analysis populations. The registry lists these secondary outcomes but does not report their estimates or analysis details.

What do the planning illustrations mean?

The record describes sample-size calculations as planning illustrations based on the observed effect, rather than the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is the planning quantity; other illustrations are expressed as participants per arm. These assumptions describe hypothetical future-study planning, not the conduct or observed power of this trial.

General statistical principle: planning calculations depend on the assumed effect, variability or event rate, significance level, allocation, and chosen power. If an assumed effect is smaller, more information is generally needed to detect it under otherwise fixed assumptions. Such calculations do not show that a completed study had a particular probability of finding a result, and they do not substitute for an observed estimate with uncertainty. Any planning rows should be read as hypothetical designs tied to their stated assumptions, not as a reinterpretation of outcomes that are absent from the registry record.

Why do multiplicity and missingness matter?

The registry lists a primary outcome and several secondary outcomes. General statistical principle: testing multiple outcomes or multiple comparisons can increase the chance of at least one apparently positive result by chance unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, hierarchy of tests, or adjusted inferential results. It is therefore not possible to determine whether any multiplicity control was planned or applied.

Missing outcome information can also affect interpretation. General statistical principle: if participants with missing outcomes differ systematically from those observed, a complete-case result may not represent the full enrolled group. The record does not report missing-data amounts, reasons, imputation methods, or sensitivity analyses for the listed outcomes. Those details are needed to evaluate how incomplete follow-up may have affected estimates.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Rovalpituzumab Tesirine and Nivolumab", "Rovalpituzumab Tesirine and Nivolumab + Ipilimumab")
n      <- c(6, 6)
events <- c(1, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Rovalpituzumab Tesirine and Nivolumab  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Rovalpituzumab Tesirine and Nivolumab + Ipilimumab  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and secondary outcomes of objective response rate, duration of response, progression-free survival, and overall survival. It also lists 6 outcome measures. The posted record reports 0 analyses. A multiplicity plan—such as a hierarchy for interpreting multiple endpoints or an adjustment to statistical testing—is not reported in the registry record. As a result, there is no basis to determine how any potential findings across outcomes would have been interpreted together.

The registry record does not report missing-data counts, reasons for missingness, methods for handling missing outcomes, or sensitivity analyses. Those omissions matter because the set of participants with observed outcomes may differ from the people enrolled or eligible for analysis. General statistical principle: assumptions about missing data can change the interpretation of estimates, particularly when missingness is related to health status, treatment discontinuation, or the outcome itself. No particular missingness pattern or method should be inferred from the record.

The primary endpoint specifies a DLT-evaluable population, defined by treatment completion or earlier discontinuation due to DLT. The number in that analysis population and the number with qualifying events are not reported in the registry record. Analysis populations for the secondary outcomes are also not reported. Without those details, readers cannot assess whether outcome analyses included all enrolled participants, only evaluable participants, or another defined group.

Likewise, no statistical analysis plan, interim analysis approach, or sample-size justification is reported in the registry record. The sample-size calculations described for planning are illustrations based on observed effects and stated assumptions, not evidence of the trial’s original design rationale or of observed power. These reporting gaps limit assessment of selective analysis, missingness, and the degree to which the posted results answer the registered questions.

12. 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 (26.7%), pleural effusion (26.7%), fatigue (16.7%), dehydration (16.7%), dyspnoea (10.0%).

The safety entries list participants at risk and participants affected by serious adverse events for each cohort. For rovalpituzumab tesirine and nivolumab, the record reports 30 at risk and 23 affected. For the cohort with ipilimumab, it reports 12 at risk and 9 affected. The listed death counts are 26 and 8, respectively. These entries describe the registry’s reported counts; they do not establish that an event or death was caused by a study drug.

The record also lists serious-event terms and percentages: malignant neoplasm progression, 26.7%; pleural effusion, 26.7%; fatigue, 16.7%; dehydration, 16.7%; dyspnoea, 10.0%; and pneumonitis, 10.0%. These entries should be read as descriptive safety information, not as a complete clinical narrative or a comparison adjusted for differences between cohorts. The record does not report event timing, individual-level overlap among terms, attribution, duration, or a statistical comparison for these figures.

Serious adverse events and deaths are separate safety concepts in the record. The listed death counts should not be interpreted as the number of deaths caused by treatment, nor should the affected counts be treated as a count of distinct events. Because allocation was non-randomized, the cohort figures do not provide a like-for-like causal comparison.

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

The registry record documents a Phase 1/2 investigation of rovalpituzumab tesirine with nivolumab, with or without ipilimumab, in adults with extensive-stage small cell lung cancer. It defines a primary safety endpoint based on dose-limiting toxicities during up to 12 weeks and names several secondary efficacy outcomes. It also gives selected serious adverse-event counts and terms. These are the elements that can be described from the posted record.

The record does not report the primary endpoint result, secondary outcome estimates, confidence intervals, or statistical analyses. Therefore, it does not allow a reader to quantify DLT frequency, assess the precision of efficacy estimates, or determine a treatment effect from the posted results. The stated study purpose and registered outcomes describe what the study sought to assess; they are not themselves evidence of an observed result.

The safety information should also be kept in its proper scope. The counts and listed terms are descriptive registry entries. They do not identify which events were attributed to a particular treatment, and the death counts do not by themselves establish treatment causality. Cohort comparisons are additionally limited by the non-randomized, sequential design. The groups are not a randomized treatment-versus-control comparison.

In general, a study result needs an estimate, a clearly defined population and outcome, and an account of uncertainty to support statistical interpretation. A registry entry that omits those results cannot establish whether an intervention is beneficial or ineffective. The appropriate conclusion is limited: the registry describes the study’s design and measures, but the posted information does not report the outcomes needed to assess efficacy or quantify the primary safety endpoint.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why study design and outcome reporting shape interpretation. The registry identifies a non-randomized, sequential design, so the listed cohorts should not be treated as equivalent groups created by random allocation. This is important when readers encounter safety counts or consider whether outcomes differed between regimens: descriptive contrasts cannot, on their own, separate treatment effects from cohort differences.

The endpoint definition also matters. A DLT count is tied to specified criteria, a defined evaluation period, and an evaluable population. Those details clarify what the outcome is intended to capture, while also making the missing endpoint count and denominator consequential. Without them, the endpoint cannot be translated into an observed frequency or an assessment of precision.

The record names response and survival outcomes as secondary measures, but does not report analyses. This distinction between registered questions and reported findings is central to evidence appraisal. Listing an outcome does not communicate its result, and a study purpose does not substitute for an estimate with uncertainty.

Finally, the planning illustrations are not trial results. They use stated assumptions to describe hypothetical future-study requirements, rather than observed power or proof that the study was designed around a particular effect. Keeping planning calculations separate from results, and descriptive safety entries separate from causal conclusions, helps prevent overinterpretation. The record’s omissions are therefore not a minor detail: they limit what can be learned from its statistical evidence.

15. 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 trial-specific limitations constrain interpretation of the registry record. First, the study is listed as non-randomized and sequential, and the registry explicitly notes that the arms are not a like-for-like control comparison. Any direct comparison between the cohorts would be vulnerable to differences beyond the regimens themselves. No adjusted comparison is reported in the registry record.

Second, the primary endpoint results are absent. The registry defines DLT and the evaluable population, but does not report the DLT count or the size of that analysis population. The secondary outcomes are listed without estimates or analysis results. The record reports 0 analyses, so the posted information does not provide inferential estimates or measures of uncertainty.

Third, the available safety information is limited. Counts of participants affected, deaths, and selected serious-event terms do not give event timing, attribution, duration, or the extent of overlap among terms. The record does not provide a statistical comparison of these safety entries. They should not be interpreted as causal treatment effects.

Fourth, the registry record does not report a multiplicity strategy, missing-data methods, analysis populations for the secondary outcomes, a sample-size justification, or interim-analysis details. The sample-size calculations described as planning illustrations are not the study’s own design rationale. Finally, the first cohort’s regimen description is truncated, so its complete maintenance schedule is not reported in the registry record. Together, these omissions limit reproducibility and prevent a full appraisal of outcome estimation and analysis choices.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer — NCT03026166.
• Registry record last updated 2020-07-17; status last verified 2020-07.
• Results first posted 2020-07-01.
• 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.

19. Record Summary

NCT03026166 is listed as a Phase 1/2, non-randomized, sequential study sponsored by AbbVie. It enrolled 42 adults with extensive-stage small cell lung cancer and is marked terminated. The record lists a cohort receiving rovalpituzumab tesirine with nivolumab and a cohort receiving those drugs with ipilimumab, including regimen descriptions for ipilimumab at 1 mg/kg and 3 mg/kg.

The primary endpoint is the number of participants with DLTs during up to 12 weeks. Secondary outcomes include objective response rate, duration of response, progression-free survival, and overall survival. The registry record does not report the primary or secondary outcome results and lists 0 analyses.

Selected serious-event counts and terms are reported descriptively. Because treatment allocation was not randomized, the cohorts are not like-for-like control groups. The posted information supports a description of the design, endpoint definitions, and selected safety entries, but not a conclusion about comparative efficacy or treatment causation.