Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer (NCT03023722), a na phase 2 study. The primary outcome is Response Rate as Measured Per RECIST 1.1 Criteria.

2. Clinical Question

The primary objective was to assess tumor response. Secondary objectives were time to progression and drug toxicity. The registry defines time to progression as the time from study treatment to RECIST 1.1 progression or death, with people going off study for other reasons censored. The record describes the primary efficacy assessment as radiological tumor evaluation using contrast-enhanced CT or MRI of the chest, abdomen, and pelvis. The clinical question is limited by the single-group design: without a concurrent control arm, the record cannot directly compare outcomes under treatment with outcomes under another treatment or no treatment.

3. Trial Design

This was an open-label, phase II, single-group study of intravenous anetumab ravtansine. The registry lists Yale University as sponsor, pancreatic cancer as the condition, and 18 as the enrollment. The study is marked completed. Start is recorded as 2017-05-11, and primary completion as 2019-08-06. The record does not specify a randomized allocation or masking; masking is listed as none and allocation as NA.

The intended population was pretreated patients with advanced pancreatic cancer who expressed mesothelin. The arm description also specifies advanced metastatic disease and measurable disease. The primary efficacy outcome was response rate according to RECIST 1.1. Its stated timeframe was from treatment start until disease progression or death, up to 3 years. The assessment description says that baseline was the prescreen scan and specifies scheduled repeat imaging at six-week intervals for the first six months, then nine-week intervals until the end of year 2, and twelve-week intervals thereafter until progression or the end of the study, whichever came first. More frequent scans could be performed if clinically indicated.

The registry says that 14 of the 18 originally enrolled subjects completed the study and were included in the primary-outcome analysis population. It also says the original intention was to follow subjects for up to 3 years, but all subjects died before that mark. The study was concluded on Dec. 11.202, after 2 years and 7 mo. These statements describe enrollment and follow-up; they do not provide the primary response count or rate. A protocol-level explanation for the analysis population, including why the other enrolled subjects were not included, is not reported in the registry record.

Because this was a single-group, open-label study, its design does not support a randomized, concurrent comparison. The registry record does not report a sample-size justification, an interim-analysis plan, or a detailed statistical analysis plan.

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: Of the 18 subjects originally enrolled, the analysis population includes the 14 subjects who completed the study. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.

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 Response Rate as Measured Per RECIST 1.1 Criteria, measured over From start of treatment until disease progression or death (up to 3 years)..

The primary endpoint is the count of participants with a response according to RECIST 1.1 criteria. The stated assessment uses radiological tumor evaluation by contrast-enhanced CT or MRI of the chest, abdomen, and pelvis. A prescreen scan is identified as the baseline measure, with repeat scans scheduled during follow-up. The registry gives the primary-outcome timeframe as from treatment start until disease progression or death, up to 3 years.

In general, a response endpoint turns imaging assessments into a prespecified clinical-trial outcome. A response rate expresses how many participants meet the response definition among the analysis population; interpretation depends on the response criteria, assessment schedule, and population used. Those details matter because response is not simply a change in symptoms or an unstructured impression: it is assessed against defined imaging criteria. The registry describes the criteria and imaging plan, but does not report the number of participants who responded, the resulting response rate, or an uncertainty interval. Thus, the endpoint definition is available, while its primary numerical result is not reported in the registry record.

The registry also lists time to progression and drug toxicity as secondary outcomes. The stated time-to-progression definition includes progression or death as an event and says that other reasons for leaving the study are censored. No time-to-progression estimate or corresponding analysis is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record is limited. It identifies a single-group, open-label phase II study and defines the primary outcome as a count of participants with a RECIST 1.1 response. It also describes the imaging assessment schedule and names time to progression and drug toxicity as secondary objectives. It does not report the analysis method used for the primary endpoint, any effect estimate, an uncertainty interval, or a significance test. The concepts below explain how such methods are generally interpreted; they should not be read as a claim that a particular analysis was conducted in this study.

What does a response count represent?

In general, a participant-count endpoint records how many people meet a prespecified outcome definition. A response rate expresses that count relative to a defined analysis population. The denominator matters: a rate calculated among all enrolled participants need not equal a rate calculated among participants who completed the study. Here, the primary-outcome population is described as the 14 subjects who completed the study, out of 18 originally enrolled, but the actual response count and rate are not reported in the registry record. The record also does not explain the handling of participants outside the stated analysis population.

The response definition is based on RECIST 1.1, and the record describes imaging by contrast-enhanced CT or MRI. In general, consistent criteria and a planned assessment schedule help make outcome assessment reproducible. This study's description specifies a baseline prescreen scan, scheduled follow-up scans, and the possibility of more frequent imaging when clinically indicated. The record does not report further details about blinded image review or other procedures intended to reduce assessment variability; such details are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical method and its assumptions. For a response proportion, an interval communicates uncertainty around the estimated proportion; it is not a guarantee that the underlying value lies within that range. The registry record does not report a response proportion or confidence interval, so there is no reported precision estimate to interpret. A p-value, if reported, would address compatibility with a specified null hypothesis under a statistical model; it would not by itself describe the size, clinical importance, or certainty of an effect. No primary-outcome p-value or null hypothesis is reported in the registry record.

The single-group design also limits what inferential methods can establish. In general, an estimate from a single group describes that group, while a comparative treatment effect requires a defined contrast. Without a concurrent comparator arm, any comparison with outcomes from elsewhere would depend on additional assumptions about comparability. The registry record does not report an external-control analysis or a comparative efficacy analysis.

What do the secondary outcomes add?

The stated time-to-progression outcome is defined from study treatment to RECIST 1.1 progression or death, with participants going off study for other reasons censored. In general, censoring indicates that the event time is not observed after a participant leaves follow-up; survival methods use the observed follow-up while relying on assumptions about censoring. The registry gives a definition but does not report a time-to-progression estimate, a survival curve, or an analysis method. It is therefore not possible to assess the observed timing of progression or death from the reported outcome information.

The secondary toxicity objective is described at a 6.5 mg/kg dose. The record includes counts for participants affected by serious and other adverse events, along with a list of serious-event terms and their reported percentages. Those counts are descriptive safety information. They do not provide a statistical comparison, and no method for comparing event rates is reported. General concepts such as confidence intervals or tests could be relevant to safety analyses, but the registry record does not report such analyses for these events.

What are the planning calculations?

In general, a sample-size calculation estimates the enrollment needed to meet a design objective under specified assumptions. It is a planning exercise, not an observed outcome and not a measure of the probability that a completed trial detected an effect. The described planning illustration uses 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. Time-to-event illustrations use a total number of events, while other illustrations express participants per arm. These assumptions describe planning calculations, not this trial's single-group design or a reported protocol justification. The trial's own sample-size justification is not reported in the registry record. Any planning values should not be interpreted as observed power or as evidence that the study demonstrated an effect.

More broadly, the registry record does not report the statistical analysis plan, the method used for the primary response analysis, an interim-analysis plan, or multiplicity procedures. Without those details and the missing efficacy results, statistical significance, precision, and robustness of the primary outcome cannot be evaluated from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary response-rate objective and secondary objectives for time to progression and toxicity. When a study evaluates multiple outcomes or multiple statistical hypotheses, multiplicity can arise: in general, the chance of at least one apparently positive finding may increase if many tests are conducted without an appropriate strategy. A prespecified hierarchy, adjustment, or other approach can help define how such results should be interpreted. The registry record does not report a multiplicity strategy, the number of hypotheses tested, or a detailed statistical analysis plan. It also reports zero analyses, so no inferential outcome analyses are available in the registry record to assess.

The primary-outcome population is described as the 14 subjects who completed the study, among the 18 originally enrolled. The registry does not report why the other subjects were not included in that analysis population, how missing response assessments were handled, or whether any additional analysis populations were used. In general, excluding participants who do not complete follow-up can change the population represented by an estimate, especially if completion is related to outcome. That is a general methodological concern, not a claim about why participants were excluded in this study.

The record states that all subjects died before the planned maximum follow-up of 3 years and that the study concluded on Dec. 11.202, after 2 years and 7 mo. It does not provide individual follow-up times, details of missing endpoint assessments, or an account of how death affected the response analysis. The handling of these issues is not reported in the registry record. As a result, readers cannot determine whether the reported completer population captures all available response information or how sensitivity to missing data was assessed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (5.6%), cognitive disturbance (5.6%), stroke (5.6%), acute kidney injury (5.6%), hypotension (5.6%).

The registry reports safety counts for the All Subjects group. Serious adverse events affected 11 of 18 subjects, and other adverse events affected 18 of 18 subjects. The record lists 18 deaths. These are participant counts, not event totals: a person may have experienced more than one event, and the record does not describe overlap among event categories. The listed serious adverse-event terms are Fever, Cognitive Disturbance, Stroke, Acute Kidney Injury, Hypotension, and Obstruction Gastric; each is reported as 5.6%.

These figures describe the categories and frequencies recorded in the registry, but they do not show when events occurred, how long they lasted, or whether the events were judged related to treatment. The record does not report causes of death or provide participant-level information, so the death count cannot be interpreted as evidence of a treatment relationship. The counts also do not establish a comparison with another treatment, because the study had no comparator arm. They should be read as descriptive safety information within this study, not as comparative estimates or proof of causation.

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

The registry record documents a phase II study intended to assess RECIST 1.1 response to anetumab ravtansine in pretreated, mesothelin-expressing advanced pancreatic cancer. It gives the study design, enrollment, stated analysis population, imaging schedule, secondary objectives, and selected safety counts. It does not report the primary response count or rate, so the central efficacy outcome cannot be quantified from the posted results.

That absence matters for statistical interpretation. A response endpoint can describe the proportion of an analysis population meeting a defined imaging criterion, but the criterion alone is not an outcome result. Without a reported numerator, rate, and uncertainty measure, readers cannot assess the magnitude or precision of response in the stated population. The record also does not report an inferential analysis that would test a prespecified hypothesis about response.

The single-group design means the study does not make a direct, concurrent comparison against a control group. Even if an outcome estimate were available, it would describe the participants studied rather than isolate a treatment effect through randomization. The registry record does not provide a comparative analysis that addresses this limitation.

The safety counts show that adverse events were recorded among participants, including serious adverse events and deaths. They do not identify the cause of death or establish that an event was caused by the intervention. The reported information is insufficient to describe event timing, individual patterns, or a comparative safety profile.

Accordingly, the record supports a factual account of the trial's conduct and the reported safety categories, while leaving the primary response result and its statistical precision unreported. It should not be read as evidence for or against treatment efficacy. The absence of a reported efficacy estimate is not the same as a finding of no response; it means that the registry record does not provide the result needed to evaluate that question.

13. Why This Trial Matters Statistically

This trial illustrates why outcome definitions and outcome results must be distinguished. The registry specifies a primary response endpoint, a RECIST 1.1 assessment framework, an imaging schedule, and a stated analysis population. Those details describe what the study set out to measure. They do not substitute for the response count, rate, or precision estimate, none of which is reported in the registry record.

It also highlights the importance of the analysis population. The record distinguishes 18 enrolled subjects from 14 subjects who completed the study and were included in the primary-outcome population. Without the response data and an explanation of how other participants were handled, readers cannot evaluate the effect of that choice on the endpoint estimate. Clear reporting of participant flow and missing-outcome handling is essential for interpreting a clinical-trial result.

The single-group, open-label design makes the limits of causal interpretation particularly relevant. Descriptive outcomes can characterize what was recorded in the study group, but a concurrent comparator is needed for a direct treatment contrast. This is a general design principle, not a conclusion about the intervention's efficacy.

Finally, the registry includes safety counts and reports that all subjects died before the intended maximum follow-up. Those details underline the need to report timing, causes, event relationships, and analysis methods alongside aggregate counts. In their absence, safety figures should remain descriptive. The record is a useful example of how a trial registration can document important design and follow-up details while leaving key statistical results unavailable.

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 principal limitation for interpreting efficacy is that the primary response count and rate are not reported in the registry record. No confidence interval, p-value, or other inferential result for the primary endpoint is reported. The stated endpoint and imaging schedule therefore cannot be used to determine the observed response experience or its precision.

The study had a single-group design and no comparator arm. This prevents a direct, concurrent comparison and limits causal interpretation. The open-label design is recorded, but the registry does not describe further procedures for response assessment, such as blinded image review; such procedures are not reported in the registry record.

The primary-outcome population comprises 14 subjects who completed the study out of 18 originally enrolled. The registry does not explain why the other enrolled subjects were not included, how missing response assessments were handled, or whether analyses using other populations were conducted. The record reports that all subjects died before the 3-year mark, but does not provide causes or timing of death. These limitations prevent assessment of how follow-up and population selection affected the primary endpoint.

Although serious adverse-event and other adverse-event counts are listed, the record does not provide event timing, participant-level overlap, or judgments about treatment relationship. It lists 18 deaths without causes. The statistical analysis plan, sample-size justification, multiplicity approach, and interim-analysis plan are not reported in the registry record. No time-to-progression estimate is reported, despite its listing as a secondary outcome. Together, these omissions constrain both efficacy and safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer — NCT03023722.
• Registry record last updated 2021-10-28; status last verified 2021-10.
• Results first posted 2021-01-22.
• 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

NCT03023722 is a completed, open-label, single-group phase II study sponsored by Yale University. It enrolled 18 subjects with pretreated, mesothelin-expressing advanced pancreatic cancer and evaluated intravenous anetumab ravtansine. The primary endpoint was response according to RECIST 1.1; time to progression and drug toxicity were secondary objectives. The stated primary-outcome population includes 14 subjects who completed the study. The registry reports serious adverse events in 11 of 18 subjects, other adverse events in 18 of 18, and 18 deaths. All subjects died before the intended 3-year follow-up mark, and the study concluded on Dec. 11.202, after 2 years and 7 mo. The primary response count and rate, inferential analyses, and detailed statistical plan are not reported in the registry record.