This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM) (NCT03175172), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03175172 |
| Phase | Phase 2 |
| Condition | Malignant Pleural Mesothelioma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Aduro Biotech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with previously treated malignant pleural mesothelioma who had failed prior anti-cancer therapy. The evaluable analysis set was defined more narrowly: participants had to receive at least one dose and have at least one evaluable post-baseline modified RECIST assessment, or discontinue because of toxicity.
Intervention
CRS-207 with pembrolizumab. The registry describes administration in 3-week cycles. For Cycle 1, pembrolizumab was given at 200 mg by intravenous infusion on Day 1, and CRS-207 was given by intravenous infusion on Day 2 at a starting dose of 1 × 10e9 colony-forming units.
Comparator
There was no concurrent control group. The study is recorded as single-group, with allocation listed as not applicable and masking listed as none. Its results therefore cannot provide a randomized, like-for-like comparison with another treatment or with a control group.
Primary question
The primary endpoint was overall response rate, based on each participant’s best overall response by modified RECIST for malignant pleural mesothelioma. The protocol-defined response rate concerned the percentage of evaluable participants whose best response was complete or partial response. The registry says that percentage was not calculated under the final statistical analysis plan. Response-category counts and an overall response-rate estimate are not reported in the registry record.
The study’s stated purpose was to evaluate safety and efficacy in adults with previously treated malignant pleural mesothelioma. It also listed disease control rate, progression-free survival, improvement in pulmonary function, and overall survival as secondary outcomes. The registry record does not report results for those outcomes in the information available for this analysis. The study enrolled 10 participants and is listed as terminated. These details describe the scope of the research question, but they do not establish how the combination compared with another option or what response rate was observed.
3. Trial Design
This was a Phase 2, single-group study of CRS-207 with pembrolizumab in adults with previously treated malignant pleural mesothelioma. The registry lists 10 participants enrolled. Allocation is recorded as not applicable, masking as none, and the model as single group. There was no randomized control arm, so the study design was suited to observing outcomes among participants receiving the combination, not to estimating a treatment contrast against a concurrent comparator.
The registry describes treatment in 3-week cycles. For Cycle 1, pembrolizumab was administered at 200 mg by intravenous infusion over 30 minutes on Day 1. CRS-207 was administered by intravenous infusion over 1 hour on Day 2, with a starting dose of 1 × 10e9 colony-forming units. Details of dosing beyond the Cycle 1 description are not reported in the registry record.
The listed study start date is 2017-05-31, and the primary completion date is 2018-01-09. The study status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or what conclusions the sponsor drew.
The primary outcome was overall response rate, assessed using best overall response by modified RECIST for malignant pleural mesothelioma. The assessment timeframe ran from the first dose until documented progression, new cancer treatment, death, or study termination, whichever came first, and was assessed up to 15 weeks. The registry also names disease control rate, progression-free survival, pulmonary function improvement, and overall survival as secondary outcomes. The detailed analysis methods for these outcomes 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.
Overall Study
| Stage | Experimental |
|---|---|
| STARTED | 10 |
| COMPLETED | 0 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Experimental |
|---|---|
| Death | 3 |
| Withdrawal by Subject | 3 |
| Lost to Follow-up | 1 |
| Study Terminated by Sponsor | 3 |
Analysis population for the primary outcome, as defined in the registry: Analysis based on subjects who received ≥1 dose of study treatment and had ≥1 evaluable post-baseline modified RECIST for MPM tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set \[EAS\]). 1 subject did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.
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.
Population: Baseline analysis provided for all subjects who were administered at least 1 dose of protocol-specified drug (the Safety Analysis Set \[SAF\]).
| Characteristic | Unit | Experimental |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 |
| Age, Categorical: >=65 years | Participants | 6 |
| Age, Continuous | years | 64.7 (SD 13.08) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 |
| Race/Ethnicity, Customized: Black or African American | Participants | 1 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race/Ethnicity, Customized: White | Participants | 7 |
| Race/Ethnicity, Customized: Other | Participants | 1 |
| Race/Ethnicity, Customized: Not Reported | Participants | 1 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 2 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 8 |
| Race/Ethnicity, Customized: Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (ORR), measured over BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Overall response rate is intended to describe the share of evaluable participants whose tumor response meets a prespecified response definition. In this study, the protocol defined a response as complete response or partial response, with best overall response determined from post-baseline modified RECIST assessments for malignant pleural mesothelioma. The registry describes a hierarchy in which complete response ranks above partial response, followed by stable disease, progressive disease, and not evaluable.
Best overall response selects the highest response category recorded for an assessed participant during the stated assessment period. This can provide a concise summary of observed tumor shrinkage under the chosen criteria. It does not, by itself, describe how long a response lasts, whether disease progression is delayed, or whether survival differs. Those questions relate to other outcomes named in the registry, including progression-free survival and overall survival.
The registry states that the protocol-specified endpoint was a percentage among evaluable participants with complete or partial response. It also states that this percentage was not calculated under the final statistical analysis plan. Instead, it says response-category counts were to be provided. The response-category counts and a calculated overall response-rate estimate are not reported in the registry record available for this analysis. As a result, the endpoint’s definition can be described, but its observed value and precision cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record does not report the primary endpoint’s response-category counts or an overall response-rate estimate. The endpoint definition is available, but a response rate cannot be read from a definition alone. Without the counts of complete responses, partial responses, stable disease, progressive disease, and participants who were not evaluable, the posted results do not establish the observed response distribution or the precision of an estimated response rate.
The study enrolled 10 participants and used a single-group design. The number enrolled sets the scale of the study, but it does not tell how many participants belonged to the evaluable analysis set or how many met the response definition. The analysis set required receipt of at least one dose and at least one evaluable post-baseline assessment, or discontinuation because of toxicity. The registry notes that one participant did not have post-baseline tumor response assessments, but does not provide the remainder of that statement in the information available for this analysis. The enrolled count should therefore not be treated as the endpoint denominator.
The absence of a concurrent comparator is also important. Any outcomes observed in a single group would describe that group during the study; they would not isolate the effect of CRS-207 with pembrolizumab from other explanations. Differences in patient characteristics, the course of disease, or care outside the study cannot be addressed through a randomized contrast in this design. The record does not report a comparison with another treatment.
The safety figures are descriptive. The registry lists 10 participants at risk for other adverse events and 10 with other adverse events, 10 at risk for serious adverse events and 4 with serious adverse events, and 3 deaths. These counts convey what was recorded for the group, but the information available does not establish the causes of the deaths or attribute them to study treatment. The listed serious-event terms and percentages likewise do not establish causality.
The study is listed as terminated, but a reason for termination is not reported in the registry record. Nor are analysis results reported for the named secondary outcomes in the information available for this analysis. Consequently, the record supports a description of design, endpoint definitions, and safety counts, but not a full assessment of efficacy, comparative effect, or the reasons the study ended.
9. Statistical Methods Explained
Statistical methods determine how observations are turned into estimates and how uncertainty is described. For this study, the registry provides the primary endpoint definition and analysis-population criteria, but does not report the response-category counts or a calculated response-rate estimate. The following concepts explain what the planned endpoint and design can support without treating unreported results as known.
What does best overall response measure?
Best overall response assigns each assessed participant the highest qualifying post-baseline response category recorded during the assessment period. The registry lists the categories in this order: complete response, partial response, stable disease, progressive disease, and not evaluable. This classification is based on modified RECIST for malignant pleural mesothelioma. The order matters because the endpoint definition uses complete and partial responses to identify participants counted as responders.
Overall response rate is a proportion: the number of evaluable participants meeting the response definition relative to the evaluable population. A proportion is informative only when its numerator and denominator are known and the population is clearly defined. Here, the registry states that the protocol specified this percentage but that it was not calculated under the final statistical analysis plan. It says response-category counts were provided for the outcome, but the actual counts are not reported in the registry record available for this analysis. No response-rate estimate can therefore be interpreted from the information available.
Why does the analysis population matter?
The registry defines the evaluable analysis set as participants who received at least one dose and had at least one evaluable post-baseline modified RECIST assessment, or who discontinued because of toxicity. This definition specifies who was intended to contribute to the endpoint assessment; it is not necessarily the same as the enrolled population. A participant who does not have an evaluable response assessment may not contribute in the same way as a participant with a measured response. Because the evaluable count and response-category counts are not reported in the registry record available for this analysis, the endpoint denominator cannot be verified.
In general, an analysis-population definition helps readers understand which participants contributed to an estimate and how events such as early discontinuation were handled. Different population rules can lead to different estimates, particularly if missing assessments are related to participants’ health or treatment experience. The registry record does not report a full missing-data procedure, an imputation method, or additional sensitivity analyses for the primary endpoint.
What can a single-group study estimate?
A single-group study can describe outcomes and adverse events observed among its participants. Without a concurrent control group, it cannot provide a randomized estimate of the difference between the combination and another treatment. This is not repaired by statistical adjustment unless a suitable design and data support such an analysis; no adjusted comparative analysis is reported in the registry record.
In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while neither alone establishes that a finding is clinically important. No confidence interval for the primary endpoint is reported in the registry record available for this analysis. Since the response estimate itself is also absent, its statistical precision cannot be evaluated.
How should planning illustrations be read?
Sample-size planning calculations are hypothetical design exercises, not evidence about what was observed in a trial. The planning illustration associated with the study uses the observed effect as its basis, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns a total number of events; for other outcomes, it concerns participants per arm.
Those assumptions describe a planning scenario rather than this study’s actual design. This trial is single-group, so an equal-allocation, two-arm illustration is not a description of the enrolled study. The registry record does not report that the trial used those assumptions to justify its enrollment, and the illustration should not be read as observed power. Sample-size planning cannot replace a reported estimate and its uncertainty.
Why do distributional assumptions matter?
General statistical methods rely on assumptions about how outcome data vary. For count data, over-dispersion means that observations vary more than a chosen model expects. If over-dispersion is present and ignored, uncertainty estimates can be too optimistic. This is a general consideration; the registry record does not report an over-dispersion assessment or a model for the primary response endpoint. The endpoint is described as a participant count by response category, rather than as a reported fitted model.
10. Multiplicity, Missing Data and Analysis Populations
The registry names one primary outcome, overall response rate, and several secondary outcomes: disease control rate, progression-free survival, improvement in pulmonary function, and overall survival. Testing or estimating several outcomes can raise multiplicity concerns. In general, when multiple statistical hypotheses are assessed, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry record does not report a multiplicity adjustment or a strategy for controlling the interpretation of multiple outcomes.
The primary endpoint has an additional reporting limitation. The registry describes the protocol-defined overall response rate as the percentage of evaluable participants with complete or partial response, but says that percentage was not calculated under the final statistical analysis plan. It states that response-category counts were provided instead; those counts are not reported in the registry record available for this analysis. Thus neither the response-rate estimate nor its precision can be assessed.
The evaluable analysis set was defined using treatment receipt, post-baseline assessment, and discontinuation due to toxicity. The record also notes that one participant did not have post-baseline tumor response assessments. The information available does not report how that participant was classified in the final analysis, nor does it give a complete account of missing assessments or the handling of not-evaluable observations. The response hierarchy includes not evaluable as a category, but its count is not reported.
More broadly, the registry record does not report imputation, sensitivity analyses, or analysis-population results for the named secondary outcomes. The number of outcome measures is listed as 5, while the number of analyses is listed as 0. These registry entries do not supply the missing outcome estimates or explain the analysis choices. No multiplicity or missing-data method should be inferred from the endpoint definitions alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Experimental | 4 | 10 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Experimental | 3 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Experimental | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Experimental |
|---|---|---|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| HYPOXIA | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| PNEUMONITIS | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| HYPOTENSION | Vascular disorders | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Experimental |
|---|---|---|
| CHILLS | General disorders | 10 of 10 |
| PYREXIA | General disorders | 9 of 10 |
| ANAEMIA | Blood and lymphatic system disorders | 5 of 10 |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | 4 of 10 |
| NAUSEA | Gastrointestinal disorders | 4 of 10 |
| HYPOTENSION | Vascular disorders | 4 of 10 |
| OEDEMA PERIPHERAL | General disorders | 3 of 10 |
| HYPOXIA | Respiratory, thoracic and mediastinal disorders | 3 of 10 |
| DECREASED APPETITE | Metabolism and nutrition disorders | 3 of 10 |
| BACK PAIN | Musculoskeletal and connective tissue disorders | 3 of 10 |
Serious events with the highest arm-level rate: dyspnoea (10.0%), hypoxia (10.0%), pneumonitis (10.0%), hypotension (10.0%).
The registry lists 10 participants at risk for serious adverse events and 4 participants with serious adverse events. For other adverse events, it lists 10 at risk and 10 affected. It also records 3 deaths. These are counts for the study group, not a comparison between treatment groups. Because the study has no concurrent control arm, the figures do not estimate an excess risk relative to another treatment.
The listed serious adverse-event terms are dyspnoea, hypoxia, pneumonitis, and hypotension, each reported as 10.0%. These are registry-listed terms and percentages; they should not be read as proof that study treatment caused the events. The information available for this analysis does not report the cause of the deaths, whether they were considered treatment-related, or the timing of each event.
Serious adverse events are not interchangeable with all adverse events: the registry reports separate affected counts for those categories. Counts also do not describe event duration, severity beyond the serious classification, or recurrence. Since the enrolled group was small and no comparator is available, these safety figures are descriptive observations rather than a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 2, single-group study evaluated CRS-207 with pembrolizumab in adults with previously treated malignant pleural mesothelioma. It defines overall response rate using best overall response by modified RECIST and gives the intended analysis-population criteria. It also reports enrollment and selected adverse-event counts. These are useful details about the study’s design and recorded observations.
The record does not report the response-category counts or a calculated overall response-rate estimate in the information available for this analysis. It therefore does not support a statement about the observed proportion of participants with complete or partial response, nor about the statistical precision of such a proportion. The primary endpoint definition should not be mistaken for an outcome result.
The single-group design also limits what can be concluded. Even if outcome estimates were available, they would describe participants treated in this study and would not constitute a randomized comparison with another treatment. The study’s enrolled count and terminated status do not establish the effectiveness of the combination, explain why the study ended, or provide a reason for an individual participant’s outcome.
The safety counts show that adverse events, serious adverse events, and deaths were recorded. They do not, on their own, establish that treatment caused an event or death. The registry information does not report cause-of-death details or the attribution of these events to treatment.
Accordingly, the most defensible interpretation is limited to the design, definitions, and descriptive safety counts that the registry reports. Efficacy estimates, comparative effects, uncertainty intervals, and detailed secondary-outcome results are not reported in the registry record available for this analysis. No claim that the treatment works or does not work follows from these registry entries.
13. Why This Trial Matters Statistically
This study is statistically instructive because its primary endpoint is clearly defined while the calculated endpoint value is not reported in the registry record available for this analysis. That distinction matters: a prespecified outcome definition tells readers what investigators intended to measure, but it is not a substitute for the observed counts, denominator, estimate, or uncertainty. Without those results, readers cannot assess the response distribution or the precision of an overall response rate.
The analysis population also illustrates why denominators deserve attention. The registry defines an evaluable set using treatment receipt, response assessment, and discontinuation due to toxicity, while noting that one participant lacked post-baseline response assessments. The enrolled count alone cannot establish the endpoint denominator. A transparent account of who was evaluable and how missing assessments were handled is important for interpreting a response proportion.
The single-group structure is another key statistical feature. It can support descriptive reporting of outcomes in the treated group, but it does not create a randomized treatment contrast. The record’s safety counts can be read as observations in that group, not as comparative estimates of harm. Likewise, sample-size planning assumptions based on a two-arm design are planning illustrations, not a description of the actual single-group trial and not evidence of observed power.
Finally, the terminated status and the absence of response estimates place limits on interpretation. The registry record does not report a termination reason or a multiplicity strategy for the listed outcomes. These gaps matter because a sound statistical reading depends not only on outcome definitions, but also on complete results, clear analysis populations, and a transparent account of the analyses performed.
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 study enrolled 10 participants and had a single-group design, with no randomized comparator. This restricts the interpretation to outcomes recorded among participants in the study and prevents a like-for-like estimate of differences against a control group. The registry lists masking as none, so the record does not describe a masked study.
The primary endpoint result is not available in the registry record for this analysis. Although the endpoint definition and analysis population are described, the response-category counts, evaluable denominator, and calculated overall response-rate estimate are not reported. The registry explicitly says that the protocol-specified percentage was not calculated under the final statistical analysis plan. The available information therefore does not permit an assessment of response frequency or precision.
The analysis-set description identifies criteria for evaluability, and the record notes that one participant had no post-baseline tumor response assessment. Further details about that participant, missing-data handling, or sensitivity analyses are not reported in the registry record. The endpoint assessment timeframe is described as up to 15 weeks, but results for that endpoint are not available in the information used for this analysis.
The registry lists secondary outcomes, but their result estimates and detailed analysis methods are not reported in the record available for this analysis. A multiplicity strategy is also not reported. The study is marked terminated, while the reason for termination is not reported in the registry record. Safety counts are available, but the cause of deaths and event attribution to treatment are not reported. These gaps limit interpretation of efficacy, safety comparisons, missing data, and the context for termination.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM) — NCT03175172.
- Registry record last updated 2019-04-04; status last verified 2019-03.
- Results first posted 2019-02-19.
- 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.
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18. Record Summary
The registry record describes NCT03175172, a Phase 2, single-group study of CRS-207 with pembrolizumab in adults with previously treated malignant pleural mesothelioma. It lists 10 participants enrolled, allocation as not applicable, masking as none, and study status as terminated. The listed study start date is 2017-05-31, with primary completion on 2018-01-09.
The primary outcome was overall response rate based on best overall response by modified RECIST. The registry states that the protocol-defined percentage of evaluable participants with complete or partial response was not calculated under the final statistical analysis plan. Response-category counts and a response-rate estimate are not reported in the registry record available for this analysis.
The registry lists disease control rate, progression-free survival, pulmonary function improvement, and overall survival as secondary outcomes. It reports 4 participants with serious adverse events, 10 with other adverse events, and 3 deaths. The reason for termination, cause of deaths, and attribution of events to treatment are not reported in the registry record.