MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) (NCT04495621), a na phase 1, phase 2 study. The primary outcome is Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab.

2. Clinical Question

The study asks whether the combination of MEN1611 and cetuximab has antitumor activity and what safety findings occur in participants with PIK3CA-mutated metastatic colorectal cancer. The official title describes patients whose disease had failed irinotecan, oxaliplatin, 5-FU and anti-EGFR-containing regimens. The registry describes a dose-confirmation phase followed by cohort expansion, rather than a randomized comparison.

The outcome is intended to describe tumor response under the study regimen, not to estimate a comparative treatment effect. Without a control group, differences from other treatments or from the course of disease cannot be attributed to the combination using this study alone. The registry record also does not report the response result, its uncertainty, or a statistical comparison. Consequently, the question can be framed from the study design and endpoint, but its answer cannot be quantified from the results information recorded.

3. Trial Design

This is an open-label, multicentre Phase Ib/II study with a sequential model. The record describes Phase 1b dose confirmation and Phase 2 cohort expansion. Participants and study personnel were not masked, and allocation is listed as not applicable. The listed regimen is MEN1611 with cetuximab; no randomized control regimen is described.

The registry reports enrollment of 29 and a completed status. The study start is recorded as 2020-07-20, and primary completion as 2024-01-12. The primary outcome timeframe is up to 37 months. These registry dates and enrollment describe the study record; they do not establish how many participants contributed to the efficacy analysis, because the primary population has additional assessment and treatment-cycle requirements.

The study concerns metastatic colorectal cancer with PIK3CA mutation. The official title describes patients failing irinotecan, oxaliplatin, 5-FU and anti-EGFR-containing regimens. The brief description characterizes the study as assessing antitumor activity and safety. It does not describe a randomized comparison or provide a basis for comparing outcomes with an external group.

Sequential dose confirmation and cohort expansion can serve different purposes within a study, but the registry record does not report the protocol details governing dose selection, cohort progression, or decisions between phases. It also does not report a statistical analysis plan, sample-size justification, or whether interim analyses were planned. The enrollment figure should therefore be read as a registry study characteristic, not as evidence that a prespecified statistical target was met.

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: Safety Population: all participants who received at least 1 dose of MEN1611. As pre-specified, RP2D data were collected and are reported for 'Phase 1b (Dose Confirmation)' cohort only.

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: Safety Population: all participants who received at least 1 dose of MEN1611.

6. Primary Endpoint

The registry lists the primary outcome as Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab, measured over Up to 37 Months.

The primary outcome is titled best overall response rate and is expressed as a percentage of participants. The registry says that best overall response was assessed according to Response Evaluation Criteria in Solid Tumors version 1.1, using local computed tomography scans or magnetic resonance imaging of the chest and abdomen, including pelvis and adrenal glands. The stated timeframe is up to 37 months.

The registry description lists complete response, partial response, stable disease and progressive disease as best overall response categories. There is a terminology issue: as a general convention, objective response rate refers to complete and partial responses, while stable disease and progressive disease are separate response categories. Since the registry description includes all four categories in its definition, the intended numerator for the reported ORR is not clear from the record alone. The outcome result and any clarification of that wording are not reported in the registry record.

Response outcomes are used in oncology studies to describe tumor status under treatment, based on specified imaging criteria. They can provide a structured measure of antitumor activity, but interpretation depends on a clear endpoint definition, the assessment schedule and how participants without evaluable scans are handled. The registry defines the primary efficacy population as participants who received at least 2 complete treatment cycles and had at least 1 disease assessment. It does not report the number meeting that definition or the primary outcome value. The endpoint therefore identifies what was intended to be measured, but the recorded information does not establish the observed response rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying what was measured, in whom, and under what comparison. The record names a response percentage as the primary outcome and defines an efficacy population based on treatment exposure and disease assessment. It does not report the response value or the statistical analysis used to estimate it. The concepts below are general explanations of how such analyses are usually read; they are not claims about methods used in this study unless the record explicitly says so.

What does a response percentage represent?

For a binary outcome, each participant is classified according to whether an event or specified response occurred. The percentage summarizes the proportion classified in the numerator among those included in the denominator. Interpreting it requires knowing exactly which outcomes count, which participants are eligible for analysis, and how missing or unevaluable observations are handled. Here the registry labels the measure ORR, but its definition includes complete response, partial response, stable disease and progressive disease. The intended numerator is therefore unclear from the registry description. A result value and a more detailed endpoint specification are not reported in the registry record.

A percentage is a point estimate, not a guarantee that the same value would be observed in another sample. A confidence interval describes uncertainty around an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry record does not report an interval for the primary outcome, so its precision cannot be assessed from the recorded result information.

Why does the analysis population matter?

The stated efficacy population includes participants who received at least 2 complete treatment cycles and had at least 1 disease assessment. This is not simply a count of everyone enrolled. A population defined by treatment exposure and assessment availability can differ from the enrolled group. If participants are left out because they discontinue early, become too unwell for assessment, or lack evaluable imaging, the resulting estimate may reflect a selected subset. Those examples are general possibilities, not explanations reported for this study. The registry does not report the number meeting the efficacy definition, exclusions from it, or the handling of missing assessments.

Analysis populations should be specified before results are interpreted. A clearly described population helps readers understand who contributes to the denominator and whether the estimate addresses the intended question. The registry record does not report whether additional populations, such as all treated participants, were used for efficacy analyses, nor does it describe sensitivity analyses for missing data.

What can a nonrandomized design estimate?

A study without randomized allocation can describe outcomes among participants receiving the study regimen. It does not, by itself, estimate the contrast that would have been observed had the same participants received a different regimen. In general, randomization helps balance measured and unmeasured prognostic factors between treatment groups. This study is open-label, lists allocation as not applicable, and does not list a randomized comparator. A comparison with outcomes from a different study or historical population would introduce additional assumptions and would not be a randomized comparison.

The sequential model and the named dose-confirmation and cohort-expansion phases describe the broad structure, but not the statistical procedures used to move between phases or choose a dose. The registry record does not report those rules. It also does not report adjustment for prognostic factors or any comparative model.

What do significance tests and multiplicity address?

A significance test assesses how compatible observed data are with a specified null hypothesis under a statistical model. A p-value does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. The record does not report a p-value for the primary outcome or a hypothesis test. With no randomized comparator listed, a treatment-versus-control test is not described.

Multiplicity arises when several outcomes, groups, time points or analyses are examined. Repeated testing can increase the chance of at least one apparently notable result under a null setting. Statistical plans may address this through prespecification or adjustment, but the registry record does not report a multiplicity strategy. It lists 8 outcome measures and 0 analyses in the record. Those listing counts do not establish which outcomes were analyzed or how their results were handled.

How should planning calculations be read?

General sample-size planning asks how many observations might be required to detect a specified effect under stated assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. It also distinguishes planning quantities for participants per arm from total events for time-to-event outcomes.

These are planning illustrations based on an observed effect, not observed power and not evidence of the study’s original design. The record does not report a trial-specific sample-size justification. Further, the listed study regimen is not part of a randomized two-arm comparison, so hypothetical equal allocation should not be mistaken for the actual design. No planning output values are reported in the registry entries.

For time-to-event outcomes, general analyses often consider how long participants remain under observation and when events occur. The registry lists progression-free survival, overall survival and duration of response as secondary outcomes, but does not report their result estimates or analysis details. No assumptions about censoring, event definitions, follow-up completeness, or modeling can be inferred from the outcome names alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and secondary outcomes covering MEN1611 plasma concentration, disease control rate, duration of response, progression-free survival and overall survival. It reports 8 outcome measures and 0 analyses. The record does not provide an analysis plan explaining which outcomes were confirmatory, how multiple outcomes or repeated assessments were handled, or whether any multiplicity adjustment was intended. A statistical plan is not reported in the registry record.

Missing-data handling is also not reported. The efficacy population is defined as participants who received at least 2 complete treatment cycles and had at least 1 disease assessment, but the record does not state how many participants met that definition or how participants without evaluable assessments were treated. It does not describe imputation, censoring rules, sensitivity analyses, or reasons for missing assessments. These details matter because the observed response percentage depends on who is included and how unavailable outcome information is addressed.

The record does not report the primary endpoint estimate, confidence interval, or p-value, and it does not provide analysis-population counts. It is therefore not possible to assess statistical precision, judge whether the analysis followed a prespecified plan, or compare the enrolled population with the analyzed population. These omissions should not be filled by assumptions about standard practice; the relevant methods are not reported in the registry record.

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: enterovesical fistula (14.3%), acute kidney injury (14.3%), gastroenteritis (14.3%), hyperglycaemia (14.3%), hypomagnesaemia (14.3%).

The safety entries are separated by study phase. For Phase 1b (Dose Confirmation), the registry lists 7 participants at risk for serious adverse events and 5 affected; for other adverse events it lists 7 at risk and 7 affected, with 7 deaths recorded. For Phase 2 (Cohort Expansion), it lists 22 at risk for serious adverse events and 11 affected; for other adverse events it lists 22 at risk and 22 affected, with 11 deaths recorded. These are registry counts and should be read as descriptive entries, not as evidence that the treatment caused an event or death.

The listed serious adverse event terms include Enterovesical fistula, Acute kidney injury, Gastroenteritis, Hyperglycaemia and Hypomagnesaemia, each reported as 14.3%, and Abdominal pain, reported as 9.1%. The record does not state the denominator or event-counting rule attached to these term percentages. It also does not report event timing, severity grades, treatment attribution, duration of exposure, or whether events overlapped within participants. The figures therefore cannot be used to infer comparative risk or causality, and phase-to-phase comparisons require caution.

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

The registry record establishes that a completed, open-label, sequential Phase Ib/II study of MEN1611 with cetuximab was registered for metastatic colorectal cancer with PIK3CA mutation. It identifies best overall response rate as the primary outcome and lists safety and additional efficacy outcomes. The record also describes the primary efficacy population and provides phase-specific safety counts.

Those details do not establish the magnitude of antitumor activity. The primary outcome result is not reported in the registry record, nor are its confidence interval or p-value. The definition itself needs clarification because the title uses ORR while the description includes stable disease and progressive disease alongside complete and partial response. Without a result and an unambiguous numerator, the response outcome cannot be quantified or interpreted as a conventional objective response rate.

The study design also limits the conclusions that can be drawn. It is open-label, allocation is listed as not applicable, and no randomized comparator is described. Observed outcomes in such a study can characterize participants receiving the combination, but they do not show how outcomes would compare under another treatment. The record does not report details that would support an adjusted comparative analysis.

The safety entries identify reported counts and event terms, but do not establish treatment causation. Attribution, severity, timing and exposure details are not reported in the registry record. Nor does the record describe missing-data methods or how the efficacy analysis population relates to all enrolled participants.

Accordingly, the posted information supports a description of the trial’s design, endpoint and recorded safety summaries. It does not support a conclusion about comparative benefit, a causal safety claim, or a precise estimate of response. Those questions require outcome and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why study design, endpoint definitions and analysis populations matter alongside an outcome label. The registry identifies a response percentage as its primary outcome, but the endpoint description includes categories that do not ordinarily all count as objective response. That discrepancy makes the operational definition important: a percentage cannot be meaningfully interpreted without knowing which categories form its numerator.

The sequential Phase Ib/II structure also illustrates the distinction between dose confirmation and cohort expansion. The registry names these phases, but does not report the rules for dose selection or phase progression. Statistical interpretation should therefore avoid assuming that the phases used the same methods or populations. The study is not randomized and no comparator is listed, so its design supports descriptive assessment rather than a direct randomized treatment contrast.

The efficacy population has a treatment-exposure and assessment requirement. This highlights how eligibility for an analysis can differ from enrollment and why missing assessments and early discontinuation need explicit handling. The registry does not report the resulting analysis-population count or those handling rules, limiting assessment of possible selection and precision.

Finally, the safety summaries are separated by phase and include both counts and selected event terms. Their interpretation depends on attribution, follow-up and denominator definitions, which are not reported for the term percentages. The record’s missing efficacy estimates and statistical methods prevent a full quantitative interpretation. These limitations make clear that a registered endpoint and descriptive safety entries are not substitutes for a transparent analysis with defined populations, estimates and uncertainty.

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 trial-specific details needed to interpret the results are not reported in the registry record. The primary response value, its uncertainty and the number of participants included in its analysis are absent. The efficacy population is defined by receipt of at least 2 complete treatment cycles and at least 1 disease assessment, but the record does not report how many participants fulfilled those criteria or how others were handled.

The primary endpoint wording is not fully clear. The measure is titled ORR, yet its description includes complete response, partial response, stable disease and progressive disease. The record does not clarify which categories counted in the numerator. Local imaging assessment is described, but details of review procedures, assessment timing and handling of unevaluable scans are not reported.

The design is open-label and does not list a randomized comparator. The record does not report the dose-selection procedures, phase transition criteria, or whether efficacy analyses differed between Phase 1b and Phase 2. It also does not report a statistical analysis plan, sample-size justification, interim-analysis approach, multiplicity method, or missing-data strategy.

For safety, event attribution, timing, severity grading and exposure information are not reported. The denominator and event-counting rules for the selected serious adverse event term percentages are also not stated. These omissions limit interpretation of the safety summaries and make comparisons across phases uncertain. The limitations are specific to what the registry record reports; unreported methods or results cannot be inferred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) — NCT04495621.
• Registry record last updated 2025-05-01; status last verified 2025-04.
• Results first posted 2025-05-01.
• 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

The registry record for NCT04495621 concerns MEN1611 with cetuximab in PIK3CA-mutated metastatic colorectal cancer. The study is described as open-label, multicentre, sequential Phase Ib/II, with Phase 1b dose confirmation and Phase 2 cohort expansion. The sponsor is Menarini Group, and the status is completed. Registry enrollment is 29; the recorded start is 2020-07-20 and primary completion is 2024-01-12.

The primary outcome is best overall response rate, with a stated timeframe of up to 37 months. The record defines an efficacy population based on treatment cycles and disease assessment, but does not report the primary result or its precision. It lists additional outcomes including disease control rate, duration of response, progression-free survival and overall survival. Phase-specific safety counts and selected serious event terms are recorded, without the attribution and analysis details needed for causal interpretation.