Sintilimab in Cancer of Unknown Primary: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sintilimab in Cancer of Unknown Primary (NCT05024968), a na phase 2 study. The primary outcome is Confirmed Objective Response Rate (cORR) by RECISTv1.1.

2. Clinical Question

3. Trial Design

This is a Phase 2, single-group clinical trial of sintilimab in advanced rare cancers, with a CUP-specific study component identified as SiARa-CUP. The record names M.D. Anderson Cancer Center as sponsor and lists the trial status as completed. The recorded start date is 2021-08-26, and the primary completion date is 2025-04-03. These record dates do not, by themselves, establish how long each participant was followed or when all outcome data were collected.

The brief summary describes a planned regimen of sintilimab 200 mg by intravenous administration, beginning on Cycle 1 Day 1 and repeating every 3 weeks. It lists stopping conditions including progressive disease, intolerable toxicity, starting new anti-tumor therapy, withdrawal of consent, loss to follow-up, death, completion of therapy, or investigator-determined reasons. Treatment was described as having a maximum duration of 24 months from the first dose. The extent to which participants followed this planned schedule is not reported in the registry record.

Tumor imaging was planned initially once every 9 weeks (± 7 days), using RECIST 1.1. The summary also describes safety and survival follow-up after treatment completion or discontinuation. It gives an expected accrual rate of approximately 2 patients per month and an expected total study duration of between 24-27 months with 6-month follow up. These are planning statements, not reported observations about actual accrual or follow-up.

Because the design has no randomized comparator and no masking, the primary endpoint is an outcome observed within a treated group rather than a comparative treatment effect. The registry record lists enrollment of 10, while the brief summary says up to 45 subjects would be enrolled. The reason for the difference between those entries is not reported in the registry record. The number included in each endpoint analysis is also not reported.

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: Participants were eligible if they were refractory or intolerant to one line of systemic therapy or had a contraindication for cytotoxic chemotherapy.

Overall Study

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 Confirmed Objective Response Rate (cORR) by RECISTv1.1, measured over 1 year.

The primary endpoint is confirmed objective response rate (cORR) by RECIST 1.1, expressed as a percentage of participants, with a stated timeframe of 1 year. In general, an objective response endpoint classifies whether a participant’s tumor measurements meet prespecified criteria for response. RECIST 1.1 is the named measurement framework in this record. Confirmation is intended to distinguish a response that is maintained on assessment from a change that is not confirmed; the record does not describe the specific confirmation procedure used in this trial.

A response rate is a proportion: the count meeting the response definition relative to the population assessed. To interpret such a result, readers need both the response count and the relevant denominator, as well as the endpoint estimate and its uncertainty. None of those primary endpoint results is reported in the registry record. The listed enrollment of 10 is not necessarily the endpoint denominator, and the record does not identify the analysis population or explain how unevaluable participants would be handled.

Response rate is used as an endpoint because it summarizes the frequency of a defined tumor response during a specified assessment period. It does not by itself describe how long a response lasts, whether survival changes, or how outcomes compare with another treatment. The registry record lists progression-free survival and overall survival as secondary outcomes, but does not report their estimates. Thus the endpoint designation is available, while the clinical result and its precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical procedure. For a response proportion, it gives a range of values compatible with the observed data and the method used to calculate the interval. It is not a guarantee that the true value lies in that particular interval, nor does it account automatically for every source of bias or uncertainty.

The primary endpoint specifies a 95% confidence interval as its dispersion measure. But the registry record does not report an endpoint estimate or interval limits. Consequently, there is no interval width to interpret and no basis for describing the precision of cORR. The listed enrollment does not allow the interval to be reconstructed, because the response count and analysis denominator are also absent.

What does a single-group result estimate?

In general, a single-group study can estimate the frequency of an outcome among participants evaluated under its study conditions. Such an estimate is descriptive of the observed group. Without a concurrent comparator, it does not directly estimate a contrast between treatments. This distinction matters because an observed response may reflect more than the treatment alone, including characteristics of the enrolled participants, outcome assessment, and follow-up.

Here, the trial is recorded as single-group, with no masking and allocation not applicable. The primary outcome is a response proportion rather than a comparison between allocated arms. No adjusted or unadjusted analyses are listed in the registry record, and no estimate is reported. Therefore, neither a within-study response estimate nor a comparative effect can be interpreted from the endpoint record.

Why do the endpoint definition and assessment schedule matter?

In general, response outcomes depend on how the event is defined, when it is assessed, and how missing assessments are handled. RECIST 1.1 is the named tumor-response framework, and imaging was planned initially once every 9 weeks (± 7 days). The primary timeframe is 1 year. These details indicate the intended assessment framework, but the registry record does not describe the trial’s exact confirmation rule, the number of assessments completed, or the analysis rules for participants without a qualifying assessment.

Assessment schedules can affect when a response is detected. If participants do not have assessments at comparable times, the opportunity to observe an event may differ. In general, transparent reporting of assessment timing and analysis rules helps readers judge whether the endpoint was applied consistently. Actual assessment completion and any deviations from the planned schedule are not reported in the registry record.

What can be learned from the posted analysis information?

The registry record lists no analyses. It names the primary and secondary outcomes, but does not provide outcome estimates, test statistics, or model results. This means there is no reported inferential analysis to interpret, such as a test of a prespecified hypothesis or a model that accounts for other factors. The statistical analysis plan, including any analysis populations and missing-data procedures, is not reported in the registry record.

In general, an analysis population defines which participants contribute to a particular outcome estimate. A safety population, for example, may be defined differently from an efficacy population; the exact definitions must come from the study record rather than inference. Here, neither the efficacy analysis population nor the safety analysis rules are described. The enrollment entry alone does not resolve those definitions.

How should planning illustrations be read?

In general, sample-size calculations describe what a hypothetical study might require under stated assumptions about an effect, significance level, allocation, and statistical method. They are planning illustrations, not observed results and not evidence that a completed study had a particular probability of detecting an effect. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with illustrations based on fractions of an observed effect. It specifies that time-to-event illustrations concern total events, while other illustrations concern participants per arm.

Those assumptions do not describe the recorded trial design, which is single-group and has no concurrent comparator. The actual study’s sample-size justification and statistical design rationale are not reported in the registry record. The observed effect used by a planning illustration is not reported as a primary endpoint estimate in the record. Any sample-size illustration should therefore be treated as a hypothetical planning exercise, not as observed power or as a description of the trial’s actual design.

In general, power is a design property under specified assumptions, not a measurement of whether a completed study “worked.” A post hoc calculation based on an observed estimate does not replace reporting the estimate and its uncertainty. Since this record does not report the cORR estimate, its denominator, or the analysis method, the primary outcome cannot be reconstructed from the available information.

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("Sintilimab 200 mg IV Every 3 Weeks")
n      <- c(10)
events <- c(4)
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  Sintilimab 200 mg IV Every 3 Weeks  10  4  40.0  12.2  73.8  16.8  68.7  16.7  69.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies confirmed objective response rate as the primary outcome and progression-free survival and overall survival as secondary outcomes. It does not report a statistical testing hierarchy, an adjustment for multiple comparisons, or any multiplicity procedure. The statistical plan is not reported in the registry record. Without this information, readers cannot determine whether multiple outcomes were intended to support separate confirmatory claims or how the risk of false-positive findings was to be managed.

In general, multiplicity arises when several outcomes or statistical tests are considered. If many tests are interpreted without an appropriate plan, the chance of at least one apparently notable result can increase. Procedures for handling multiplicity can be specified in advance, but no such procedure is described in the record. No analyses or outcome estimates are listed, so there are no reported tests to assess for multiplicity in any case.

The record also does not report missing-data rules, analysis populations, or how participants without response assessments would be classified. In general, missing outcome information can affect a response proportion if participants with unobserved outcomes are excluded or classified differently. The direction and size of any resulting effect depend on the missingness pattern and analysis approach; neither is reported.

Although the brief summary describes follow-up and imaging plans, it does not establish that all planned assessments occurred. The record gives no account of loss to follow-up, withdrawals, evaluability, or endpoint-specific denominators. Therefore, it is not possible to judge the extent or handling of missing endpoint data from the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists one group, “Sintilimab 200 mg IV Every 3 Weeks.” For serious adverse events, it reports 0 affected among 10 at risk. For other adverse events, it reports 3 affected among 10 at risk. It also lists 5 deaths. These are counts as recorded, not estimates of comparative risk.

The record does not provide the specific serious or other adverse event terms in the listed group, and it gives no information about event severity beyond the serious-event classification, timing, duration, recurrence, or relationship to treatment. It also does not state whether the deaths were considered related to treatment or give their causes or timing. The meaning of the at-risk denominators beyond the recorded group entry is not further explained.

In general, zero recorded events does not prove that an event cannot occur; it means no affected participants were recorded in that group for that category. Counts also need context about observation time and completeness of event reporting, which are not detailed. The listed deaths should not be treated as a treatment-related count without reported attribution. These safety entries do not substitute for a full safety analysis or establish how the groups would compare under another treatment, since there is no comparator group.

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

The registry record describes a completed Phase 2, single-group study of sintilimab for CUP and identifies confirmed objective response rate by RECIST 1.1 as its primary endpoint. It also describes the planned dosing and assessment schedule, lists secondary survival outcomes, and records selected adverse-event and death counts. These details clarify the question the study was intended to address and the framework in which outcomes were to be assessed.

The record does not report the primary endpoint result. No response count, denominator, percentage, or confidence interval is available. It also gives no estimates for progression-free survival or overall survival. As a result, the record does not establish the observed response frequency, how precise an estimate might be, or what the survival outcomes were. The enrollment entry does not provide those missing results and should not be substituted for the analysis population.

Even if a single-group response estimate were available, it would describe the outcome among participants in that study rather than a randomized comparison. Without a concurrent comparator, it cannot by itself show how outcomes would differ under another treatment or under a different care condition. The study design does not support a like-for-like controlled comparison.

The safety counts are also limited: the record lists 0 serious adverse events among 10 at risk, 3 other adverse events among 10 at risk, and 5 deaths, without event details or attribution. These entries do not establish causation or comparative safety. Overall, the registry record supports a description of the planned and recorded study features, but does not provide enough outcome information to quantify the primary result or make a comparative statistical interpretation.

14. Why This Trial Matters Statistically

This trial is statistically notable as a single-group Phase 2 study in a population described as having a rare cancer. Its primary endpoint is a defined response proportion, and the record names RECIST 1.1 and a 1-year timeframe. These features make the intended outcome measurable in principle, while the absence of a concurrent comparator sets a clear limit on the kinds of conclusions a response proportion could support.

The distinction between planned enrollment and recorded enrollment is also important for interpreting evidence. The brief summary describes an aim to enroll up to 45 subjects, while the registry record lists enrollment of 10. The reason for that difference is not reported. Nor does the record state which participants contributed to the primary endpoint analysis. This illustrates why an enrollment figure alone is not enough to understand an endpoint estimate: readers also need the outcome count, denominator, and handling of participants without an assessment.

Statistical interpretation depends not only on naming an endpoint but on reporting its result and uncertainty. A confidence interval is specified for cORR, yet the interval and its estimate are absent from the record. The completed status does not remove that reporting gap. Likewise, the listed secondary outcomes do not yield interpretable findings in the absence of analyses or estimates.

The record therefore highlights a practical principle in clinical-trial reporting: design information and outcome information answer different questions. Design details explain what investigators planned to measure; estimates and uncertainty describe what the study observed and how precisely. Both are needed for a reader to evaluate the statistical evidence. In this case, the recorded design and limited safety counts can be described, but the primary efficacy result cannot be evaluated quantitatively.

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.

The most direct limitation is that the registry record does not report the primary endpoint estimate, response count, denominator, or confidence interval. It names cORR by RECIST 1.1 and a 1-year timeframe, but without the result there is no basis for assessing the observed response frequency or its precision. The record also lists no analyses, so there are no statistical results to interpret.

The single-group design has no concurrent comparator, allocation is listed as not applicable, and masking is listed as none. Therefore, the design cannot provide a randomized comparison. Any descriptive outcome, if reported, would need to be interpreted as an observation in the treated group rather than a direct estimate of a difference between treatment strategies.

The record lists enrollment of 10, while the brief summary describes plans to enroll up to 45 subjects. The reason for the difference is not reported in the registry record. The endpoint analysis population and endpoint-specific denominator are also not reported, so it is not possible to determine how enrollment relates to the primary analysis.

Important analysis details are absent, including the statistical plan, analysis populations, missing-data rules, endpoint confirmation procedure, and multiplicity approach. The record does not report actual treatment exposure, completed imaging assessments, or the extent of follow-up. These gaps limit assessment of how closely observed study conduct matched the planned schedule.

Safety reporting is also limited to group counts and does not provide adverse-event terms, event timing, or attribution for the listed deaths. Finally, the registry record does not provide estimates for the named secondary outcomes. These limitations constrain interpretation of both efficacy and safety and should not be resolved by assumptions about unreported methods or results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sintilimab in Cancer of Unknown Primary — NCT05024968.
• Registry record last updated 2026-02-25; status last verified 2026-02.
• Results first posted 2026-02-25.
• 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

The registry record describes a completed Phase 2, single-group study of sintilimab for cancer of unknown primary. M.D. Anderson Cancer Center is listed as sponsor. The recorded start date is 2021-08-26, primary completion date is 2025-04-03, and enrollment is listed as 10. The brief summary describes a plan to enroll up to 45 subjects.

The primary endpoint is confirmed objective response rate by RECIST 1.1, with a stated 1-year timeframe and a 95% confidence interval. The record lists progression-free survival and overall survival as secondary outcomes, but provides no outcome estimates or analyses. It also lists 0 serious adverse events among 10 at risk, 3 other adverse events among 10 at risk, and 5 deaths, without event details or attribution.

The design has no concurrent comparator, and the primary endpoint result, analysis denominator, and statistical analysis plan are not reported in the registry record. The available information supports describing the trial design and recorded safety counts, but not quantifying or comparing the primary outcome.