A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC (NCT03547999), a randomized phase 2 study. The primary outcome is 3-year Overall Survival (OS) Rate From Metastasectomy.

2. Clinical Question

The clinical question concerns adding a vaccination sequence to a perioperative regimen that includes nivolumab and systemic chemotherapy. The registry describes a randomized, parallel-arm Phase II study in people whose metastatic colorectal cancer was limited to the liver and considered resectable. Both treatment plans included reassessment for surgical resection after treatment; the experimental plan added MVA-BN-CV301 and FPV-CV301 at different stages.

The primary endpoint focuses on survival at a specified follow-up point after metastasectomy. This is distinct from the registry’s secondary overall survival endpoint, which is listed as measured from registration. The primary result therefore has a defined time origin and a restricted analysis population: participants who received one dose of protocol therapy and were completely resected. It should be interpreted in that context rather than as an outcome for every randomized participant.

The registry record reports 100.0% for both arms, with 7 participants in the control analysis and 9 in the experimental analysis. It does not report a confidence interval, a p-value, or a comparative estimate for this endpoint. The result can therefore be described as the posted percentage in each analysis group, but it does not by itself establish whether the regimens differ.

3. Trial Design

This was a randomized, parallel-arm Phase II trial with no masking. The registry lists metastatic colorectal cancer as the condition and describes the target population as people with resectable, hepatic-limited disease. The brief summary states that the study planned to enroll 78 patients. Actual enrollment is listed as 17. The registry status is terminated; the reason for termination is not reported in the registry record.

The control arm was assigned mFOLFOX6 and nivolumab every 2 weeks for 4 cycles. The experimental arm began with 2 MVA-BN-CV301 vaccinations, given 2 weeks apart with nivolumab, followed by 4 FPV-CV301 vaccinations given 2 weeks apart alongside mFOLFOX6 and nivolumab. After Cycle 4, the summary describes reassessment for resection. People considered resectable were to undergo surgery with the goal of complete resection. The summary also describes continued follow-up when complete resection was not possible, with an additional candidate randomized to the corresponding arm. Details of later post-operative treatment are incomplete in the registry summary.

The registry lists the study start as 2018-06-26 and primary completion as 2024-03-13. The primary endpoint is 3-year overall survival from metastasectomy. The results list 7 participants in the control analysis and 9 in the experimental analysis, each with a posted value of 100.0%. These analysis counts should not be conflated with overall enrollment: the endpoint’s stated population includes only participants who received one dose of protocol therapy and were completely resected.

Further design details, including the allocation ratio, are not reported in the registry record. The record identifies randomization but does not provide enough information to reconstruct how the sequence was generated or concealed. No masking was used. The stated study plan and the posted results should be kept distinct: the former describes intended treatment and enrollment, while the latter gives the reported endpoint values for the registry-defined analysis groups.

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

Analysis population for the primary outcome, as defined in the registry: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Overall survival was defined as all patients receive one dose of protocol therapy and are completely resected.

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 3-year Overall Survival (OS) Rate From Metastasectomy, measured over 3 years.

The primary endpoint is the 3-year overall survival rate from metastasectomy. The registry defines it as the percentage of patients who are still alive at 3 years. Overall survival is a time-to-event outcome: it concerns whether a participant has died by a specified point in follow-up, rather than whether a tumor meets a response criterion or whether surgery was feasible.

The endpoint is measured from metastasectomy, so its time origin is the surgical procedure. The registry separately lists a secondary 3-year overall survival outcome measured from registration. Those endpoints do not use the same starting point and should not be treated as interchangeable.

The stated primary analysis population consists of patients who received one dose of protocol therapy and were completely resected. This restriction matters: the posted result is not a rate for all randomized participants. In the registry results, the control group has 7 participants and a value of 100.0%; the experimental group has 9 participants and a value of 100.0%. No confidence interval or comparative test is reported for this endpoint.

Generally, a fixed-time survival rate offers an interpretable summary of survival status at a clinically defined follow-up point. Its precision depends on the amount of outcome information and the analysis method. The registry record does not report enough detail to assess the precision of these percentages or how censoring and missing follow-up were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary percentage at a fixed follow-up time: each person in the stated analysis population either was alive at 3 years from metastasectomy or was not. The registry reports the outcome as a percentage of participants. The posted values are 100.0% for the control group and 100.0% for the experimental group. The corresponding analysis counts are 7 and 9.

What does a percentage summarize?

Generally, a percentage summarizes the proportion of an analysis group meeting a defined outcome. It is easy to interpret, but it does not communicate how much uncertainty surrounds the estimate. That uncertainty is especially relevant when an analysis group is small. A confidence interval is a general statistical tool for expressing uncertainty around an estimated proportion or treatment effect. No confidence interval is reported for this primary endpoint in the registry record.

The observed percentages are not, by themselves, a comparative effect measure. A comparison would generally be accompanied by an estimate of the difference or another suitable contrast and an uncertainty measure. Neither a comparative estimate nor a p-value is reported for this endpoint. The record therefore supports describing each group’s posted result, but not quantifying the precision of an arm-to-arm contrast.

Why does the analysis population matter?

The registry states that the overall-survival analysis population includes all patients who received one dose of protocol therapy and were completely resected. This is narrower than the full group enrolled or randomized. Generally, restricting analysis to a post-randomization subgroup can change the question being answered, because entry into that subgroup depends on events after assignment. The result describes survival in the registry-defined subgroup, not an estimate that automatically applies to all randomized participants.

The record does not report a separate primary-endpoint analysis for all randomized participants. It also does not provide a flow of participants through treatment, surgery, and follow-up. Although it describes re-evaluation for surgery and continued follow-up when complete resection was not possible, the posted primary endpoint’s stated population is limited to completely resected participants who received protocol therapy. The exact handling of participants outside that population is not reported in the registry record.

How should missing follow-up be considered?

Generally, survival analyses can account for participants whose outcome is not observed through the full follow-up period by using censoring methods. The registry record does not report the analysis method, censoring rules, amount of missing follow-up, or whether vital status was available for all members of the stated analysis population. It is therefore not possible to assess how incomplete follow-up may have affected the posted percentages. The registry definition gives a 3-year time point but does not describe the operational details used to derive the rates.

The outcome is measured from metastasectomy, which makes the timing of surgery part of the endpoint definition. The record also lists a secondary 3-year overall survival outcome from registration. In general, changing the time origin can change the population’s follow-up window and the interpretation of the rate; the two registry outcomes should therefore be kept distinct. The analysis method for either time-to-event outcome is not reported in the registry record.

What do the planning illustrations represent?

General sample-size calculations are planning exercises, not summaries of what happened in a trial. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the illustration is described in terms of total events; other outcome types are described in terms of participants per arm. These planning outputs are not observed power and are not evidence that the study was adequately powered.

The record does not report the trial’s own sample-size justification or enough information to reproduce a trial-specific calculation. It lists planned enrollment of 78 in the brief summary and actual enrollment of 17, but that alone does not establish why the target was chosen or whether the trial’s design assumptions were met. A planned sample size and an observed analysis count answer different questions.

How do randomization and masking affect interpretation?

Randomization is intended, in general, to make treatment groups comparable at assignment. The registry identifies the study as randomized and parallel, but details of sequence generation, allocation concealment, and allocation ratio are not reported in the registry record. The record states that there was no masking. Lack of masking can matter for outcomes influenced by assessment or care decisions; the primary endpoint is survival status, but the record does not describe how outcome ascertainment was conducted.

The registry gives no primary-endpoint inferential analysis, and it lists no analyses in the posted analysis count. The absent details limit evaluation of the statistical approach. The posted percentages remain descriptive results for the defined groups; they should not be supplemented with an assumed test, confidence interval, or model.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Arm A - Control", "Arm B - Experimental")
n      <- c(7, 9)
events <- c(7, 9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm A - Control  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Arm B - Experimental  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 secondary outcomes: 3-Year Recurrence Free Survival (RFS) Rate, Overall Response Rate (ORR), Patients Amenable to Complete Resection/Ablation, Perioperative Surgical Outcomes, 3-Year Overall Survival (OS) Rate From Registration, and Pathologic Response Rate. These are in addition to the primary 3-year overall survival endpoint measured from metastasectomy. The two overall-survival outcomes have different stated time origins.

When a study evaluates multiple outcomes, the chance of finding an apparently notable result across the set can differ from the chance attached to a single prespecified comparison. This is a general multiplicity issue. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting secondary outcomes, or a statistical analysis plan describing how multiple endpoints were to be handled. It is therefore not possible to determine from the record whether or how multiplicity was addressed.

The registry defines the primary endpoint analysis population as patients who received one dose of protocol therapy and were completely resected. It does not report a separate primary result for all randomized participants. The record also does not provide participant flow or detailed counts for exclusion from this analysis population. Because the endpoint population is defined using post-randomization events, the result pertains to that selected population and should not be generalized automatically to all enrolled or randomized participants.

Missing-data handling is not reported in the registry record. The amount of missing survival follow-up, the method for handling censoring, and the status of participants without complete follow-up are also not reported. The record does not describe imputation or sensitivity analyses. These omissions limit assessment of whether missing outcome information could have affected the endpoint estimate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal infection (12.5%), acute kidney injury (12.5%), colonic obstruction (12.5%), dehydration (12.5%), hypoxia (12.5%).

The registry reports serious adverse events separately by arm. In the control group, 6 participants were affected among 8 at risk; in the experimental group, 5 were affected among 9 at risk. For other adverse events, the record reports 8 affected among 8 at risk in the control group and 9 among 9 at risk in the experimental group. It reports 0 deaths in the control group and 1 in the experimental group. These are the registry’s counts; they are not the same denominators as the primary endpoint analysis groups.

The listed serious-event terms are ABDOMINAL INFECTION, ACUTE KIDNEY INJURY, COLONIC OBSTRUCTION, DEHYDRATION, HYPOXIA, and PNEUMONITIS, each reported at 12.5%. The registry record does not provide additional context in the registry record about event timing, recurrence, severity grading, or attribution to treatment. The death count does not establish whether the death was related to treatment.

Safety counts should be read as descriptive reports for the listed groups, not as a randomized safety comparison or a complete account of every possible adverse event. Differences in the number at risk and the absence of further analysis details limit direct comparisons between arms.

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

The posted primary result is a 3-year overall survival percentage of 100.0% in each arm, measured from metastasectomy among participants who received one dose of protocol therapy and were completely resected. The registry lists 7 participants in the control analysis and 9 in the experimental analysis. This is the result for the specified endpoint population, not a summary of all 17 enrolled participants.

The result does not show that the regimens are equivalent. Equal percentages in the posted analysis groups are not a formal equivalence finding, and the registry reports no confidence interval, p-value, or comparative treatment-effect estimate for the primary endpoint. The precision of the percentages and the range of plausible arm differences are therefore not available from the record.

Nor does the result establish what would have occurred for people who did not receive protocol therapy, were not completely resected, or did not have observed follow-up. The primary analysis population excludes people who do not meet its stated criteria. The registry does not report a separate all-randomized result for this endpoint or describe missing follow-up handling.

The trial is randomized, but the available primary result is an endpoint percentage for each defined analysis group rather than a reported randomized comparison with uncertainty. The record also states that the study was terminated and gives actual enrollment of 17, compared with planned enrollment of 78 in the summary. The reason for termination is not reported in the registry record, and the posted information does not establish the effect of termination on follow-up or analysis.

These results are best understood as descriptive registry findings. They neither demonstrate a treatment benefit nor establish a lack of benefit. The record gives too little information to assess comparative precision, missing-data effects, or the statistical analysis used to produce the reported percentages.

14. Why This Trial Matters Statistically

This trial raises a statistical question common to perioperative oncology studies: how to interpret an outcome measured after treatment and surgery when the primary analysis includes only people who received treatment and were completely resected. That population definition is essential to the meaning of the result. It distinguishes the endpoint estimate from an outcome among all randomized participants.

The comparison is also challenging because the registry reports a fixed-time percentage in each arm without an uncertainty interval or a comparative estimate. A percentage is straightforward to communicate, but a result without precision information cannot show how much uncertainty surrounds the estimate. The posted values are 100.0% in both groups, with analysis counts of 7 and 9. The record does not report a test or interval that would support a more detailed comparison.

The study was randomized and parallel, which establishes the broad framework for comparing two treatment strategies. However, details that would help assess the comparison, such as allocation ratio, allocation concealment, and the handling of participants outside the primary analysis population, are not reported in the registry record. The trial is marked terminated, with actual enrollment of 17 and planned enrollment of 78 stated in the summary. The termination reason is not reported.

The endpoint’s timing also matters. Overall survival from metastasectomy answers a different question from the separately listed secondary overall survival outcome from registration. Clear time origins are important when interpreting follow-up and comparing outcomes across analyses.

Statistically, the record illustrates why outcome definitions, analysis populations, precision estimates, and missing-data methods all matter alongside the observed percentage. Without those elements, the posted result can be accurately described but supports only a limited assessment of comparative evidence.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint analysis is restricted to participants who received one dose of protocol therapy and were completely resected. The posted percentages therefore do not represent all enrolled participants. The registry record does not report a separate result for all randomized participants or provide detailed participant flow through treatment, resection, and follow-up.

Precision and comparative inference are limited by the absence of a confidence interval, p-value, or treatment-effect estimate for the primary endpoint. The record does not describe the statistical method used to calculate the fixed-time survival rates, how censoring was handled, or how missing follow-up was addressed. These details are not reported in the registry record.

Actual enrollment is listed as 17, while the brief summary states that the study planned to enroll 78. The registry marks the study terminated but does not report the reason. It is not possible to determine from the record whether termination altered follow-up, endpoint ascertainment, or the planned analysis.

Although the study is identified as randomized and parallel, allocation ratio, sequence-generation procedures, and allocation concealment are not reported. No masking was used. The registry also does not report a multiplicity strategy for the primary and secondary outcomes, or a trial-specific sample-size justification.

The safety results provide counts and a list of serious-event terms, but the record does not report details on event timing, repeated events, treatment attribution, or severity grading beyond the serious-event classification. As a result, both efficacy and safety interpretation is necessarily limited to the registry’s posted descriptive information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC — NCT03547999.
• Registry record last updated 2025-07-22; status last verified 2025-07.
• Results first posted 2025-07-22.
• 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.

19. Record Summary

The registry describes a randomized, unmasked, parallel-arm Phase II trial of perioperative CV301 vaccination with nivolumab and systemic chemotherapy for resectable hepatic-limited metastatic colorectal cancer. The control arm received mFOLFOX6 and nivolumab; the experimental arm added MVA-BN-CV301 and FPV-CV301 vaccinations to its regimen.

The stated primary endpoint was 3-year overall survival from metastasectomy, defined as the percentage alive at 3 years. The analysis population was participants who received one dose of protocol therapy and were completely resected. The posted values were 100.0% for the control group, with 7 participants, and 100.0% for the experimental group, with 9 participants.

The registry lists planned enrollment of 78, actual enrollment of 17, and study status as terminated. It does not report the termination reason, a confidence interval or comparative test for the primary endpoint, or detailed missing-data methods. Six secondary outcomes are listed, including recurrence-free survival, response, resection/ablation, perioperative outcomes, overall survival from registration, and pathologic response.