Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2 (NCT04935359), a randomized phase 3 study. The primary outcome is Randomized Part: Overall Survival (OS).

2. Clinical Question

The study was intended to evaluate the efficacy and safety of adding NIS793 to standard-of-care chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma. The registry summary describes the biological rationale as exploring whether blockade of Transforming Growth Factor β could reduce fibrosis and restore chemo-sensitivity, with the longer-term aim of improving overall survival and other clinically relevant outcomes. That rationale is a study objective, not evidence that those effects occurred.

The primary outcome was overall survival, measured from randomization or start of treatment until death from any cause. The registry reports arm-specific median survival estimates and confidence intervals. It does not report a hazard ratio or a sponsor-reported statistical comparison of survival between randomized arms. The posted results therefore allow a descriptive comparison of the median estimates, but do not establish the result of a formal treatment-effect test.

3. Trial Design

daNIS-2 was a randomized, quadruple-masked, parallel-group Phase III study sponsored by Novartis Pharmaceuticals. Its total enrollment was 511, and the registry marks the study as completed. The recorded study start was 2021-09-30, and primary completion was 2024-08-13.

The study included a safety run-in and a randomized part. In the randomized part, Arm A received NIS793 with gemcitabine and nab-paclitaxel; Arm B received placebo with gemcitabine and nab-paclitaxel. The primary outcome population was the randomized-part Full Analysis Set. The posted primary outcome includes 245 participants in each arm. The registry describes analysis according to randomized assignment, a principle that preserves the original randomized comparison even if participants do not follow their assigned treatment exactly.

The safety run-in included 21 participants in its dose-intensity outcome. The run-in and randomized groups serve different purposes and should not be treated as interchangeable comparisons. The randomized comparison is the relevant basis for interpreting the trial’s primary question; the run-in group was not randomized against the placebo arm.

The registry describes NIS793 and placebo treatment as stopped on 7-Jul-2023. It does not give further context for that change in the available record. Although the masking level is described as quadruple, which individuals or roles were masked is not reported in the registry record. Details of the randomization procedure, allocation concealment, and the protocol’s rationale for the planned enrollment are also 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dose-Determining Set (DDS) - The DDS consisted of all participants in the safety run-in part who met the minimum exposure criterion and had sufficient safety evaluations after 4 weeks of treatment or experienced a DLT during the first 4 weeks of treatment.

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 Randomized Part: Overall Survival (OS), measured over From randomization up to death, assessed up to approximately 34 months.

Overall survival measures the time from randomization or start of treatment to death from any cause. It is a time-to-event outcome: participants can have different lengths of follow-up, and some may still be alive at the end of their observed follow-up. For participants not known to have died, the registry says survival was censored at the last date they were known to be alive. Censoring retains information up to that last known date without treating the participant as having died then.

The registry reports the median, the time by which half of the relevant survival experience has elapsed under the endpoint’s estimation approach, along with a 95% confidence interval. Overall survival is used as a direct measure of time to death from any cause and does not depend on a judgment that a particular cause of death is related to the study treatment.

The recorded timeframe was from randomization up to death, assessed up to approximately 34 months. The arm-specific medians describe each randomized group; they are not themselves a complete estimate of the relative effect between groups. A comparison such as a hazard ratio, its confidence interval, and a corresponding inferential result would be needed to characterize the relative time-to-event effect in the sponsor’s analysis. Those results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall survival is a time-to-event endpoint. Unlike a simple outcome recorded once for every participant, time-to-event analysis accounts for when an event occurs and for participants whose event has not been observed by the end of their follow-up. The registry defines the event as death from any cause and says participants not known to have died were censored at their last known date alive. General explanation: censoring indicates that an event time is not observed after a particular point; it does not mean that the event occurred at that point.

What does the median describe?

The posted statistic is the median overall survival for each randomized group. It describes the midpoint of the estimated survival-time distribution, rather than the survival time of a typical individual in every other respect. The median is useful because it gives an interpretable time summary for a time-to-event outcome. It does not describe the entire survival curve, and two groups’ medians alone do not capture all possible differences across follow-up.

The registry reports a 95% confidence interval for each median. General explanation: a confidence interval expresses the uncertainty associated with an estimate under the statistical method used. A narrower interval generally indicates greater precision than a wider one, though precision depends on the analysis and data. The intervals should be read alongside the estimates, not as a substitute for a direct comparison between treatment groups. The registry does not state the method used to estimate the medians or their confidence intervals.

Why is a direct comparison important?

Randomization establishes the comparison between assigned groups, but an inferential analysis is still needed to quantify the relative treatment effect and its uncertainty. Time-to-event comparisons commonly use information from the event times and censoring patterns. General explanation: a hazard ratio is one possible relative-effect summary; it compares event rates over time under the assumptions of the selected model. No sponsor-reported hazard ratio or primary-comparison p-value appears in the registry record. The method used for the sponsor’s primary comparison is not reported in the registry record, so a particular model or assumption should not be inferred.

The record identifies the primary analysis population as the Full Analysis Set in the randomized part. It includes participants assigned study treatment by randomization and analyzed according to that assignment. This description is consistent with retaining randomized group assignment for the primary comparison. The registry does not give a detailed participant flow or explain any exclusions, if applicable.

How should recalculated comparisons be treated?

For selected secondary outcomes, the posted results include unadjusted recalculations from summary statistics. Such recalculations are not the sponsor’s reported analyses. They use only the available summaries and do not necessarily reflect the trial’s prespecified model, covariate adjustments, estimand, or handling of missing data. The registry lists no reported analyses for those comparisons. These calculations can help describe the posted summaries, but they should not be treated as a replacement for the sponsor’s analysis.

The sample-size illustrations are also distinct from the study’s design justification. They use observed effects, equal allocation, a two-sided significance level of 0.05, and a normal approximation, and consider stated fractions of the observed effect. They are planning illustrations, not observed power and not evidence that the trial was designed around those effects. For time-to-event outcomes, the illustration concerns a total number of events; for other outcomes it expresses participants per arm. The trial’s own sample-size justification and assumptions are not reported in the registry record.

General explanation: over-dispersion occurs when outcome variability is greater than a model assumes, which can make uncertainty estimates too small if it is ignored. The registry record does not identify an over-dispersion issue or a model for the primary endpoint, so no such adjustment can be attributed to this trial. More broadly, details of analysis populations beyond the primary Full Analysis Set, the handling of protocol deviations, and the statistical procedures for censoring and missing data are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies overall survival in the randomized part as the primary outcome and lists multiple secondary outcomes. It does not report how the statistical testing plan addressed multiplicity across the primary and secondary endpoints, whether any endpoint hierarchy was used, or whether secondary tests were adjusted. Without that information, unadjusted secondary p-values should not be interpreted as if they controlled the chance of false-positive findings across the full set of outcomes.

The available registry record does not include a complete statistical analysis plan, the primary comparison model, or sponsor-reported inferential results for overall survival. Interim analyses, any associated stopping rules, and the protocol’s sample-size justification are not reported in the registry record. The sample-size illustrations based on observed effects do not establish the design assumptions used by the sponsor.

The primary analysis population is described as the randomized-part Full Analysis Set, analyzed according to randomized assignment. For survival, participants not known to have died were censored at their last known date alive. This is the only explicit missing-follow-up rule in the primary outcome description. Other missing-data procedures, sensitivity analyses, and the handling of missing secondary outcome measurements are not reported in the registry record.

The total enrollment is 511, while the posted primary outcome reports 245 participants in each randomized arm. Safety outcomes use their own at-risk counts and distinguish on-treatment from post-treatment periods. The record does not provide enough participant-flow detail to reconcile all analysis populations or explain changes in denominators. These omissions limit assessment of completeness and of whether the analysis matched every planned procedure; they do not, on their own, establish that the analysis was biased.

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: vomiting (9.5%), blood loss anaemia (5.6%), escherichia urinary tract infection (5.6%), embolism (5.6%), anaemia (5.4%).

The registry reports serious adverse events and other adverse events in separate on-treatment and post-treatment groups. In the randomized on-treatment groups, serious adverse events were reported for 144 of 239 participants in Arm A and 110 of 241 participants in Arm B. Other adverse events were reported for 228 of 239 participants in Arm A and 236 of 241 participants in Arm B. The post-treatment groups have different at-risk counts and should be read as separate observation periods, not as direct extensions of the on-treatment denominators.

The safety run-in has its own group counts. The registry also lists serious adverse-event terms with percentages, including vomiting, blood loss anaemia, Escherichia urinary tract infection, embolism, anaemia, and acute myocardial infarction. The population and denominator used for that list are not reported in the registry record, so those percentages should not be assigned to a randomized arm without further information.

These counts describe events recorded in the registry; they do not by themselves establish that study treatment caused an event. The deaths listed by treatment period are not identified as adverse-event-related deaths in the available record. Differences in follow-up periods and at-risk counts also matter when comparing safety summaries. Further detail about event definitions, attribution, severity grading, and exposure-adjusted comparisons is not reported in the registry record.

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

The registry result establishes that the randomized study recorded different median overall survival estimates in its two treatment groups, with confidence intervals indicating uncertainty around each estimate. It does not establish the result of a formal between-group survival test because a sponsor-reported comparison estimate and its inferential results are not reported in the registry record. A descriptive difference between medians should not be recast as proof of a treatment effect.

Nor does a confidence interval answer every question about clinical importance. It describes uncertainty in an estimate under a statistical method; it does not determine whether a difference matters to patients, account for every potential source of bias, or describe all treatment outcomes. The registry’s stated biological rationale and study objective explain why the comparison was undertaken, but they do not determine the outcome.

The study was randomized and the primary population was analyzed according to assigned treatment, which provides the basis for a controlled comparison. The posted result still needs to be interpreted in light of missing analysis details, including the primary comparison method, the multiplicity approach, and the extent of follow-up. Those details are not reported in the registry record. The completed status means the study is recorded as completed, not that every statistical detail or result is available.

The secondary summaries provide context about response, disease control, treatment exposure, and adverse events. They address related but distinct questions and carry additional uncertainty, particularly because the registry does not report sponsor analyses or multiplicity adjustments for those outcomes. A careful reading separates the descriptive estimates from inferential claims and distinguishes registry reporting from conclusions that would require additional analysis or documentation.

13. Why This Trial Matters Statistically

This trial illustrates why a primary endpoint must be interpreted together with the form of its reported estimate. Overall survival is a time-to-event outcome, and the registry provides a median and confidence interval for each randomized group. Those summaries are useful and directly interpretable, but they are not equivalent to a relative-effect estimate or a formal test of the randomized comparison.

It also illustrates the difference between a trial’s intended question and the information available in a registry record. The study was designed to compare NIS793 plus chemotherapy with placebo plus the same chemotherapy, and its primary outcome was overall survival. Yet the registry record does not report the sponsor’s survival comparison statistic, the primary analysis method, or the multiplicity plan. Those omissions constrain the statistical conclusions that can be drawn from the posted numbers, even though arm-specific estimates are available.

Finally, the record separates a safety run-in from the randomized part and reports safety by treatment period. Keeping these groups and periods distinct avoids treating unlike populations or follow-up windows as if they were a single randomized comparison. The secondary summaries and planning illustrations can offer context, but they do not replace the primary randomized analysis. This makes daNIS-2 a useful example of how to distinguish descriptive results, exploratory recalculations, and confirmatory evidence.

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.

Several limitations are specific to the available record. The randomized primary outcome gives arm-specific median overall survival and confidence intervals, but does not report the sponsor’s hazard ratio, confidence interval for a between-arm effect, p-value, or primary model. The comparison is therefore less fully characterized than it would be with a reported relative-effect estimate and analysis details.

The record identifies the Full Analysis Set and describes censoring for participants not known to have died, but does not provide a detailed participant flow, death counts for the primary analysis, follow-up completeness, or sensitivity analyses. It also does not describe how missing data were handled for secondary outcomes. These gaps make it difficult to assess the completeness and robustness of the outcome analyses from the registry record alone.

Although multiple secondary outcomes are listed, detailed results are available only for selected measures, and sponsor-reported analyses are not listed. The multiplicity strategy is not reported. Recalculated secondary comparisons based on summary statistics are unadjusted and cannot replace the study’s prespecified analyses. Likewise, planning illustrations based on observed effects are not the trial’s sample-size rationale.

The overall enrollment and outcome denominators differ, and the record does not explain participant flow across the safety run-in, randomized analysis, and safety periods. Serious adverse-event terms are listed with percentages, but the associated population and denominator are not stated. The record also does not identify which roles were masked, describe the allocation procedure, or give details of treatment exposure after the recorded treatment stop. These are reporting limitations; they should not be mistaken for proof of a flaw in trial conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2 — NCT04935359.
• Registry record last updated 2026-05-19; status last verified 2026-04.
• Results first posted 2026-05-19.
• 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

daNIS-2 was a completed, randomized, quadruple-masked, parallel-group Phase III study in first-line metastatic pancreatic ductal adenocarcinoma. It compared NIS793 plus gemcitabine and nab-paclitaxel with placebo plus the same chemotherapy. Total enrollment was 511.

The primary endpoint was overall survival in the randomized-part Full Analysis Set. The registry reports median overall survival of 9.2 months in Arm A and 11.2 months in Arm B, with arm-specific 95% confidence intervals. A sponsor-reported between-arm survival estimate and statistical comparison are not reported in the registry record.

Selected secondary results include dose intensity, overall response rate, and disease control rate. The record also reports adverse-event counts by treatment period. The statistical analysis plan, multiplicity handling, sample-size justification, and detailed missing-data procedures are not reported in the registry record.