First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors (NCT02937116), a non-randomized phase 1 study. The primary outcome is Number of Participants Experiencing Dose-limiting Toxicities (DLTs).

2. Clinical Question

The registry describes a first-in-human study of IBI308, also called sintilimab in its outcome and safety descriptions. Its stated purposes include assessing safety, tolerability and efficacy, as well as pharmacokinetics, pharmacodynamics and immunogenicity. The primary endpoint focuses on dose-limiting toxicities during the first treatment cycle, a period used in early-phase research to characterize short-term tolerability at different dosing regimens.

The interventions were not a single uniform regimen. Some cohorts received IBI308 alone, while others received it alongside different chemotherapy combinations. The listed cohorts also concern different tumor types. Consequently, the central question is descriptive: what safety and other outcomes were recorded for participants receiving these regimens? It is not a randomized estimate of whether IBI308 is better than a control treatment. Numerical results for the primary endpoint and detailed efficacy results are not reported in the registry record.

3. Trial Design

This was a phase 1, open-label, multicenter, non-randomized study with a parallel model. The registry lists enrollment of 233 and describes the population as subjects with selected advanced solid tumors. The study began on 2016-10-19, reached primary completion on 2020-09-30, and is listed as completed.

The study included phase 1a dose groups and phase 1b cohorts. In phase 1a, participants received IBI308 at 1mg/kg, 3mg/kg, or 10mg/kg intravenously every 2 weeks, or 200mg intravenously every 3 weeks. In phase 1b, some cohorts received IBI308 200mg every 3 weeks as monotherapy. Other cohorts paired IBI308 with chemotherapy regimens, including combinations involving cisplatin and pemetrexed, cisplatin and gemcitabine, oxaliplatin and capecitabine, cisplatin and etoposide, or irinotecan and 5-FU. The listed regimens varied by cohort and tumor type.

Open-label means treatment assignment was not masked from participants and study personnel. Non-randomized means participants were not assigned to these regimens through random allocation. Cohort membership and treatment therefore cannot be interpreted as if they arose from a randomized comparison. Differences in tumor type, regimen, and other participant characteristics can complicate comparisons across cohorts.

The registry describes treatment continuation rules for some cohorts, including stopping for progression or unacceptable toxicity, and in some cohorts a limit of up to 24 months. Several chemotherapy cohorts included induction treatment followed by maintenance for participants who had not progressed. The complete protocol and a full statistical analysis plan are not reported in the registry record, so design details beyond the registered descriptions should not be inferred.

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 12 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants in Parts A1 to A4 who received ≥1 dose of study treatment and either 1) had a DLT in Cycle 1 or 2) received ≥90% of the prescribed dose of Sintilimab in Cycle 1 and completed all safety evaluations ≥28 days after the first administration of Sintilimab without experiencing DLT. Per protocol, cohort A to H were not analyzed.

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 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Dose-limiting Toxicities (DLTs), measured over Up to 28 days in Cycle 1.

The primary endpoint is the number of participants experiencing dose-limiting toxicities (DLTs), with the timeframe listed as up to 28 days in Cycle 1. A DLT endpoint is used in early-phase studies to identify clinically important toxicities during initial exposure to a study regimen. It helps characterize short-term tolerability and informs the evaluation of dose or regimen choices; it is not, by itself, a measure of long-term safety or treatment benefit.

The registry specifies an endpoint population for Parts A1 to A4. It includes participants who received at least one dose of study treatment and either had a DLT in Cycle 1, or received at least 90% of the prescribed sintilimab dose in Cycle 1 and completed all safety evaluations at least 28 days after the first administration without a DLT. This definition means that the endpoint denominator is not automatically all enrolled participants. The registered description does not establish how many participants met this population definition.

The endpoint is a count of participants, rather than a time-to-event measure or a continuous measurement. Its interpretation depends on knowing both the number who experienced a DLT and the number evaluated under the endpoint definition. Neither numerical primary endpoint results nor the endpoint denominator are reported in the registry record. The registry record therefore identifies what was intended to be measured, but does not permit an estimate of the observed DLT frequency.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is a count of participants with dose-limiting toxicities during Cycle 1, up to 28 days. This is a binary event at the participant level: a participant either meets the DLT outcome definition or does not. The endpoint is then expressed as a number of participants. For a frequency or proportion to be interpretable, the number evaluated under the endpoint definition is also needed. The registry describes that population for Parts A1 to A4 but does not report its size or the numerical endpoint result.

What does a DLT endpoint capture?

General explanation: an early-cycle DLT endpoint is intended to capture specific toxicities during an initial treatment period, as defined by the study protocol. It is useful in early-phase research because it focuses attention on short-term tolerability when a treatment regimen is first evaluated. The endpoint does not capture every aspect of safety. Adverse events occurring later, events not meeting the protocol’s DLT criteria, and longer-term outcomes require separate description. The detailed DLT criteria are not reported in the registry record.

The registry’s population definition includes participants in Parts A1 to A4 who received at least one dose and either experienced a DLT in Cycle 1 or received at least 90% of the prescribed sintilimab dose in Cycle 1 and completed all safety evaluations at least 28 days after the first administration without a DLT. This definition conditions inclusion on treatment exposure and completion of safety evaluations for participants without a DLT. The number included and the handling of participants who did not meet these conditions are not reported in the registry record.

How should cohort comparisons be understood?

The study is non-randomized, open-label, and organized into parallel groups that received different dose schedules or combinations. General explanation: randomization is used to make treatment groups more comparable on average, including for factors that may not be measured. Without random allocation, observed differences between groups may reflect participant characteristics, tumor type, treatment combinations, or other differences rather than the effect of IBI308. An open-label design can also affect treatment delivery, reporting, and assessment, particularly for outcomes that involve judgment.

Here, the group descriptions include different tumor populations and chemotherapy regimens, as well as IBI308 monotherapy. This means the cohorts do not form a like-for-like control comparison. The registry record explicitly notes that this is not a randomized comparison. Cohort-specific counts can describe what was recorded in those groups, but they do not establish comparative treatment effects.

What can significance tests and confidence intervals tell readers?

General explanation: a significance test evaluates how compatible observed data are with a specified statistical model and null hypothesis. A p-value does not measure the size or clinical importance of an effect, and it does not by itself establish causation. A confidence interval describes uncertainty around an estimate under the analysis assumptions. Neither method removes bias caused by non-random treatment allocation or incomplete outcome reporting.

The registry record lists zero analyses. It does not report a primary endpoint estimate, p-value, confidence interval, or detailed statistical analysis plan. Those methods therefore cannot be used to assess the primary endpoint from the registry information. The analysis population for secondary outcomes, missing-data approach, and any adjustment or modeling choices are also not reported in the registry record.

What do the planning calculations mean?

General explanation: a sample-size calculation is a planning exercise that asks how much information a future study might need under chosen assumptions. It is not an observed treatment effect or a measure of the probability that a completed study has detected a true effect. The registry’s planning illustration is described as a recalculation from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration is based on a total number of events; for other outcomes, it is expressed as participants per arm for 80% power or participants per arm for 90% power.

Those assumptions are not the study’s stated design rationale. The registry record does not report that the trial was designed with those planning assumptions, nor does it report a sample-size justification. Because the trial is non-randomized and does not provide a like-for-like control comparison, planning calculations based on an observed effect should not be read as evidence from a randomized comparison. Sample-size illustrations are planning quantities, not observed power.

Why does over-dispersion matter in general?

General explanation: over-dispersion occurs when variation in data is greater than a statistical model assumes. If a model ignores that extra variation, uncertainty estimates can be too small and statistical conclusions can appear more precise than the data warrant. The registered primary endpoint is a participant count, and the registry does not report a model for that endpoint or an analysis that addresses over-dispersion. It would therefore be inappropriate to claim that this issue was assessed in this study.

In short, the registry record makes the endpoint and broad study structure understandable, but does not report the inferential methods or numerical results needed to evaluate an estimated treatment effect. The general statistical concepts above explain how such methods work; they are not claims that those analyses were performed in this trial.

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("Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1)", "Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2)", "Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3)", "Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4)")
n      <- c(3, 3, 3, 3)
events <- c(0, 0, 0, 0)
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  Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan describing how multiple outcomes or comparisons were handled. It lists the primary DLT endpoint and secondary outcomes that include PFS, DOR, TTR, OS, and pharmacokinetic measures. Testing or estimating many outcomes can increase the chance of apparently notable findings arising by chance when formal significance testing is used. General methods to address this include prespecifying a limited set of confirmatory comparisons or adjusting for multiple testing. Whether any such approach was used is not reported in the registry record.

The registry record lists zero analyses. Numerical results, p-values, confidence intervals, and analysis populations for the efficacy and pharmacokinetic outcomes are not reported in the registry record. Without those details, the extent of outcome reporting and the role of exploratory analyses cannot be assessed.

Missing-data methods are also not reported in the registry record. The record gives a specific endpoint population for Parts A1 to A4, requiring either a DLT or a high level of prescribed-dose receipt and completion of safety evaluations for participants without a DLT. It does not report how many participants met that definition, how participants with incomplete assessments were handled, or how missing measurements for secondary outcomes were treated. General explanation: missingness can affect an estimate when the availability of data is related to participants’ health, treatment exposure, or outcomes. The direction and extent of any such effect cannot be determined without information on missing data and the analysis approach.

The registry enrollment is 233, but that figure does not establish the denominator for every endpoint or cohort. The outcome-specific populations and the treatment of missing observations are not reported in 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lung infection (66.7%), pancreatitis acute (33.3%), pneumonitis (33.3%), respiratory failure (33.3%), biliary tract infection (33.3%).

The registry lists serious adverse events, other adverse events, and deaths separately for each treatment group. For serious adverse events, the group descriptions include the number at risk and the number affected. These are group-level descriptive counts, not randomized comparisons. The denominators differ by group, and the tumor populations and regimens differ as well.

The record identifies lung infection as a serious adverse event term with 66.7% beside it. Pancreatitis acute, pneumonitis, respiratory failure, biliary tract infection, and blood bilirubin increased are each listed with 33.3%. The registry does not report the denominator or calculation details for these percentages alongside the terms, so they should not be interpreted as percentages of all enrolled participants or compared as if they arose from a common population.

Serious adverse events are distinct from the broader other-adverse-event counts listed for each group. The registry also lists deaths by group, but does not identify those counts as deaths caused by study treatment. These figures do not, on their own, establish a causal relationship or comparative safety. The registry record does not provide a complete narrative explaining event timing, severity grading, attribution, or the handling of overlapping events.

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

The record documents a completed phase 1 study evaluating IBI308 as monotherapy and with chemotherapy in subjects with selected advanced solid tumors. It names short-term dose-limiting toxicities as the primary endpoint and gives a specific Cycle 1 timeframe. It also registers secondary efficacy and pharmacokinetic outcomes and lists adverse events by treatment group. These details establish what the study set out to evaluate and what kinds of safety information were recorded.

The record does not report the numerical result for the primary DLT endpoint. It therefore does not support a statement about the observed number or frequency of DLTs in the endpoint population. Numerical secondary outcome findings are also not reported in the registry record. The listed adverse event counts and terms are descriptive and cannot establish that IBI308 caused an event, or that one regimen was safer or more effective than another.

The non-randomized, open-label design is important to interpretation. The groups were not assigned through randomization, and their tumor types and regimens varied. Any differences among cohort outcomes could reflect those differences or other factors. In the absence of a randomized control group and reported comparative analyses, the study record does not establish a causal treatment effect relative to a control.

General explanation: early-phase studies can characterize treatment exposure and generate information for further study, but a DLT count alone does not answer questions about longer-term safety or efficacy. Assessing precision also requires estimates and uncertainty measures, such as confidence intervals, which are not reported for the primary endpoint in this record.

The record consequently supports a description of the trial’s design, endpoint, treatment groups, and registered safety listings. It does not support a conclusion that the treatment works or does not work, nor a reliable estimate of comparative benefit or harm.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way it combines early dose evaluation with multiple tumor-specific cohorts and chemotherapy combinations. The primary endpoint focuses on dose-limiting toxicities during Cycle 1, an outcome suited to describing short-term tolerability in an early-phase study. The registered study then includes a broader set of secondary outcomes, from response and survival measures to pharmacokinetic measures.

That breadth makes clear why the study design and analysis population matter. Results from different cohorts would not automatically be comparable: participants had different tumor types and could receive different chemotherapy combinations. Because allocation was non-randomized, cohort contrasts are vulnerable to differences beyond the treatment regimen. A descriptive count can be useful for documenting observed events, but it does not isolate a causal effect.

The registry record also illustrates the distinction between a registered endpoint and a reported result. It describes the DLT outcome and the population definition, but does not report the numerical primary result or its denominator. Without those quantities, the central safety endpoint cannot be interpreted quantitatively. Similarly, listed secondary outcomes do not establish efficacy in the absence of numerical findings and analysis details.

For statistical readers, the central lesson is to separate design information, observed safety listings, and treatment-effect evidence. The design and adverse event listings offer context, while the lack of reported endpoint results and inferential methods limits conclusions about frequency, precision, and comparison. The record is useful for understanding the study’s scope, but incomplete for evaluating its primary outcome.

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 principal limitation for interpreting this trial record is the absence of numerical primary endpoint results. Although DLTs are identified as the primary outcome and the Cycle 1 timeframe is specified, neither the count of participants with DLTs nor the number evaluated under the stated endpoint definition is reported in the registry record. Without both, the primary safety outcome cannot be quantified.

The registry record also does not report numerical results for the listed secondary efficacy and pharmacokinetic outcomes. It gives no confidence intervals, p-values, or detailed analysis methods. Statistical plan details, including any approach to multiplicity, missing data, or outcome-specific analysis populations, are not reported in the registry record.

The design imposes additional interpretive limits. Allocation was non-randomized and masking was absent. Treatment groups differed in tumor type and in whether IBI308 was given alone or with chemotherapy. The groups therefore cannot serve as like-for-like randomized comparators. Factors associated with cohort selection or disease characteristics could contribute to observed differences.

The serious adverse event listings are descriptive, and the registry does not report denominator details for the percentages accompanying the top serious event terms. The listed deaths are not identified as treatment-caused. Detailed event timing, attribution, and the relationship of adverse events to treatment are not reported in the registry record.

Finally, enrollment does not establish the number analyzed for each outcome. The record’s endpoint-specific eligibility definition is narrower than enrollment, and the endpoint population size is not reported. The registry record thus supports careful description of design and registered outcomes, but not a complete evaluation of observed efficacy, safety rates, or treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors — NCT02937116.
• Registry record last updated 2022-10-14; status last verified 2022-09.
• Results first posted 2021-02-21.
• 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

This completed phase 1, open-label, multicenter study evaluated IBI308 alone and with chemotherapy in subjects with selected advanced solid tumors. It was non-randomized, with parallel treatment groups and enrollment of 233. The study began on 2016-10-19 and reached primary completion on 2020-09-30.

The primary endpoint was the number of participants experiencing DLTs up to 28 days in Cycle 1. The registry record defines an endpoint population for Parts A1 to A4 but does not report the numerical primary result or the number evaluated. Secondary outcomes include PFS, DOR, TTR, OS, and pharmacokinetic measures; their numerical results are not reported in the registry record.

Serious adverse event counts and terms, other adverse event counts, and deaths are listed by group. These data are descriptive and do not establish causal or randomized comparisons. The registry record does not report the statistical analysis plan, missing-data methods, or detailed analysis results.