A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202) (NCT04225117), a non-randomized phase 2 study. The primary outcome is Cohorts 1-8: Confirmed Overall Response Rate (ORR) (Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1 Per Investigator Assessment.

2. Clinical Question

3. Trial Design

EV-202 is an open-label, multicenter, nonrandomized, parallel, phase 2 study. The registry lists enrollment of 329 and describes nine cohorts organized by cancer type and histology. Its status is active, not recruiting. The recorded study start is 2020-03-10, and the primary completion date is 2025-02-25.

Enfortumab vedotin is the study drug in cohorts 1–8. The described schedules for those cohorts use intravenous infusions on days 1, 8, and 15 of each 28-day cycle. Cohort 6 describes participants being reallocated by disease type and histology into cohorts 7 or 8; the treatment descriptions then identify gastric and esophageal adenocarcinoma, including gastroesophageal junction adenocarcinoma, in cohort 7, and esophageal squamous cell carcinoma in cohort 8. Cohort 9 studies enfortumab vedotin with pembrolizumab, on schedules using days 1 and 8 for enfortumab vedotin and day 1 for pembrolizumab in each 21-day cycle.

Because allocation is nonrandomized and the cohorts represent different tumor groups, the design does not provide a randomized comparison between treatments. Open-label conduct means treatment assignment is not masked. The primary endpoint is specified for cohorts 1–8; cohort 9 has its own secondary outcome measures. The registry describes 12 outcome measures, but records zero analyses. A protocol-level statistical analysis plan, including any rationale for the enrollment target or interim analysis procedures, is 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.

Before assignment: Participants who met all inclusion criteria and none of the exclusion criteria were enrolled in the study. Participants initially enrolled into Cohort 6 were reallocated based on disease type and histology into Cohorts 7 or 8. Data for all participants who had been enrolled into Cohort 6 is presented in either Cohort 7 or 8 based on the histology of the participant's tumor.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Response Evaluable Set (RES) in Cohorts 1-8: all FAS participants who had measurable disease at baseline per investigator assessment and either had at least 2 postbaseline response assessments or were no longer in the follow-up of response at the time of analysis.

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: Full Analysis Set (FAS): All enrolled participants who received any amount of study intervention.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Cohorts 1-8: Confirmed Overall Response Rate (ORR) (Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1 Per Investigator Assessment, measured over Up to 20.04 months.

The primary endpoint is confirmed overall response rate (ORR) for cohorts 1–8. It is the percentage of participants in the Response Evaluable Set whose tumor response was confirmed as a complete response or partial response under RECIST v1.1, based on investigator assessment. The stated timeframe is up to 20.04 months.

ORR is a binary-outcome summary: each eligible participant either meets the confirmed response definition or does not. Expressing the result as a percentage gives a direct description of the proportion with a documented tumor response in the defined analysis population. Requiring confirmation distinguishes the endpoint from a single assessment that has not been confirmed. RECIST v1.1 supplies standardized response categories, while investigator assessment identifies who determines the response in this endpoint.

The registry specifies an exact binomial confidence interval using the Clopper–Pearson method. A confidence interval communicates the uncertainty around an estimated response percentage; it is not a range of outcomes expected for individual participants. However, the record does not report the observed ORR, the number of confirmed responders, or the confidence interval. The endpoint definition is available, but its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response endpoint count?

Confirmed ORR is a binary percentage. For each participant in the specified response-evaluable population, the endpoint records whether a complete response or partial response was confirmed under RECIST v1.1. The percentage represents the proportion meeting that definition. The registry names investigator assessment as the assessment source and says the response must be confirmed. It does not report the actual numerator or denominator for the endpoint analysis.

Binary endpoints reduce each participant’s response history to whether the defined event occurred. That makes the result comparatively straightforward to communicate, but it does not convey how long a response lasted or the full pattern of tumor change. Duration of response is listed separately among the secondary outcomes, as are disease control rate and progression-free survival.

What does the exact binomial interval mean?

The registry specifies a Clopper–Pearson confidence interval based on the binomial distribution. In general, a confidence interval describes uncertainty around an estimated event percentage, given the observed number of events and the size of the analysis population. The exact binomial method is one approach to calculating such an interval, particularly suited to a binary response outcome. An interval is not a guarantee that the true value lies within its limits, nor does it describe the range of individual responses.

The method cannot be interpreted numerically without the underlying response count and analysis denominator. Neither an ORR estimate nor its interval is reported in the registry record, so precision cannot be evaluated. The record also does not report whether any additional adjusted or sensitivity analyses were conducted.

Why is the analysis population important?

The endpoint population is the Response Evaluable Set in cohorts 1–8. The registry defines it as FAS participants with measurable disease at baseline per investigator assessment who either had at least two postbaseline response assessments or were no longer in response follow-up at the time of analysis. This rule makes evaluability dependent on baseline measurement and follow-up assessment conditions. It is not interchangeable with the overall enrollment count.

In general, excluding people without sufficient response assessments can make an endpoint easier to calculate, but it also means that the reported percentage would apply to the defined evaluable group rather than automatically to everyone who entered a study. The registry’s eligibility definition is available; detailed handling of missing or unevaluable response assessments beyond that definition is not reported in the registry record.

How should the cohort structure affect interpretation?

This is a nonrandomized, open-label study with disease-specific cohorts. Random allocation is not used to make groups comparable, and masking is absent. Thus, differences among cohort results would be descriptive unless supported by an appropriate analysis and assumptions; they should not be treated as randomized comparisons. Cohort 9 includes pembrolizumab in addition to enfortumab vedotin, unlike the treatment description for cohorts 1–8. Differences between those cohorts could not isolate the contribution of either drug from the information in the registry record.

Investigator assessment is the stated basis for the primary response endpoint. In general, open-label assessment can be susceptible to expectations or judgment, although RECIST criteria provide a defined framework for classifying response. The registry record does not report whether independent central review was also performed.

What do the planning illustrations represent?

Planning illustrations based on an observed effect are not observed power and are not evidence that the trial achieved a particular power. The stated illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is total events; for other outcomes, it is participants per arm. These are general planning calculations, not a substitute for the trial’s own design rationale. The rationale for the enrollment target and any trial-specific sample-size justification are not reported in the registry record.

Over-dispersion is a general concern when outcome variability exceeds what a chosen statistical model assumes. It can make standard errors and confidence intervals too optimistic if the model does not accommodate the extra variability. The primary endpoint is described using an exact binomial method, but the registry record does not report a model-based analysis or an over-dispersion assessment. No conclusion about such an assessment can be drawn from the listed endpoint method.

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("Cohort 1: HR+/HER2- Breast Cancer", "Cohort 2: TNBC Cancer", "Cohort 3: Squamous NSCLC", "Cohort 4: Non-squamous NSCLC", "Cohort 5: Head and Neck Cancer", "Cohort 7: EAC")
n      <- c(45, 42, 23, 43, 46, 42)
events <- c(7, 8, 1, 7, 11, 4)
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  Cohort 1: HR+/HER2- Breast Cancer  45  7  15.6  6.5  29.5  7.7  28.8  7.8  28.9
ARM  Cohort 2: TNBC Cancer  42  8  19.0  8.6  34.1  10.0  33.3  10.0  33.4
ARM  Cohort 3: Squamous NSCLC  23  1  4.3  0.1  21.9  0.8  21.0  1.0  21.1
ARM  Cohort 4: Non-squamous NSCLC  43  7  16.3  6.8  30.7  8.1  30.0  8.2  30.1
ARM  Cohort 5: Head and Neck Cancer  46  11  23.9  12.6  38.8  13.9  37.9  13.9  38.0
ARM  Cohort 7: EAC  42  4  9.5  2.7  22.6  3.8  22.1  3.9  22.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: the primary confirmed ORR for cohorts 1–8 and secondary measures that include duration of response, disease control rate, progression-free survival, overall survival, and treatment-emergent adverse events, with some outcomes also specified for cohort 9. When many outcomes or cohorts are examined, the chance of at least one apparently unusual result can increase. Statistical plans sometimes address this through a prespecified hierarchy or multiplicity adjustment. Such a plan, including whether any adjustment was used, is not reported in the registry record.

The record lists zero analyses. It therefore does not report the estimates, confidence intervals, or statistical tests for the primary or secondary endpoints. It also does not state whether interim analyses took place, or how any such analyses would affect interpretation; those details are not reported in the registry record.

Missing response data require particular care because the primary endpoint is defined in a response-evaluable population with baseline and follow-up assessment conditions. The record gives those inclusion criteria, but does not report further rules for missing assessments, unevaluable participants, or sensitivity analyses addressing missingness. The available definition should not be expanded into an assumed missing-data method.

The registry does not report a full analysis plan describing analysis populations for every secondary outcome, covariate adjustment, subgroup analyses, or multiplicity procedures. FAS appears within the stated definition of the response-evaluable population, but further details about that population and how it was used for other outcomes are not reported in the registry record. These omissions limit assessment of whether the analyses followed a prespecified plan and how robust any results would be to alternative analytic choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (8.7%), tumour haemorrhage (7.3%), syncope (7.3%), acute respiratory failure (7.3%), abdominal pain (4.9%).

The registry lists safety counts for cohorts 1–5 and 7–9. For each listed group, it reports the number at risk and the number affected by serious adverse events, the number at risk and number affected by other adverse events, and deaths. For example, cohort 1 lists 45 at risk for serious events and 12 affected; it lists 45 at risk for other events and 44 affected, with 36 deaths. These are reported counts, not calculated rates or comparisons.

The listed serious-event counts vary across disease-specific cohorts, whose group sizes also differ. They should therefore be read within their own cohort context rather than as a head-to-head comparison. The registry does not report a randomized control group, exposure-adjusted event rates, or a causal attribution for each event. A recorded death count should not be assumed to mean that every death was caused by treatment.

The registry also names COVID-19 at 8.7%, tumour haemorrhage at 7.3%, syncope at 7.3%, acute respiratory failure at 7.3%, abdominal pain at 4.9%, and sepsis at 4.9% among the top serious adverse event terms. These percentages describe the listed terms as recorded; the record does not provide enough information to infer comparative risks or causality from them.

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

The posted information describes a phase 2, nonrandomized study organized into cohorts by cancer type, the primary response endpoint for cohorts 1–8, and safety counts for listed cohorts. The endpoint definition is specific: confirmed complete or partial response by RECIST v1.1, assessed by investigators, in a response-evaluable population. That information clarifies what an eventual ORR estimate would represent.

The record does not report the primary endpoint result. It therefore does not establish the observed response percentage, how many participants met the response definition, or the precision of an estimate. Nor does it report analyses of the secondary outcomes. The absence of reported analyses in the registry record should not be interpreted as evidence for or against an effect; it means those results are not reported there.

The study’s nonrandomized structure also limits what comparisons could mean. Cohorts comprise different tumor types, and cohort 9 includes pembrolizumab with enfortumab vedotin. Outcomes across those groups would not constitute a like-for-like comparison of treatments. Without randomized allocation or a reported comparative analysis, differences cannot be attributed to a treatment contrast on the basis of this record.

Safety figures provide counts of participants affected by events in each listed cohort and selected serious-event terms. They are useful for understanding what was recorded, but they do not by themselves establish that treatment caused an event or quantify risk relative to a control group. Overall, the registry record supports a description of the study’s design and planned measures, plus the posted safety counts; it does not provide a basis for judging the efficacy estimate or its uncertainty.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and analysis populations are central to interpreting clinical research. ORR may sound like a simple percentage, but its meaning depends on which responses count, whether they require confirmation, the response criteria used, who assesses them, and which participants enter the denominator. EV-202 specifies each of these elements for its primary endpoint: confirmed complete or partial response, RECIST v1.1, investigator assessment, and the Response Evaluable Set in cohorts 1–8.

The cohort structure also matters statistically. Participants are grouped by cancer type rather than randomized between treatment options. This can be appropriate for describing activity across distinct disease settings, but it does not create a controlled comparison. A result from one tumor cohort cannot automatically be compared with a result from another as though the participants had been assigned to alternative treatments under comparable conditions.

Finally, a registry record can provide detailed definitions without reporting analyzed outcomes. Here, the endpoint method and safety counts are stated, while the record lists zero analyses. This distinction is important: knowing how a result was meant to be measured is not the same as having an estimate, and an estimate without its uncertainty would not establish its precision. Reading the design, analysis population, and reporting status together helps keep descriptive information separate from conclusions that require reported results and appropriate comparisons.

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.

Several limitations are specific to the information recorded for this study. The primary ORR analysis is defined, but the registry record does not report its estimate, response count, denominator, or confidence interval. It also lists zero analyses, so there are no reported results for the secondary efficacy outcomes named in the record. The safety counts do not fill that gap: they describe recorded events but do not provide an efficacy comparison.

The nonrandomized, open-label design limits comparative interpretation. The cohorts represent different tumor types, and cohort 9 uses a combination regimen while cohorts 1–8 describe enfortumab vedotin. No like-for-like randomized control comparison is reported. The registry does not report whether independent central review was used alongside investigator assessment.

The primary analysis population requires measurable baseline disease and specified response follow-up conditions. The record does not report additional missing-data rules or sensitivity analyses, so the potential effect of missing or unevaluable assessments cannot be assessed. It also does not report a statistical analysis plan detailing multiplicity control, interim analyses, or the rationale for the enrollment target. These details should not be inferred from the endpoint description or planning illustrations.

Safety interpretation is also limited by the absence of a randomized comparator and by the presentation of counts within disease-specific cohorts. The registry record does not provide exposure-adjusted rates or establish causation for individual events. Thus, the reported counts and listed serious-event terms should be read as descriptive registry information rather than comparative estimates of treatment-related risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202) — NCT04225117.
• Registry record last updated 2026-09-23; status last verified 2026-08.
• Results first posted 2026-04-13.
• 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

EV-202 is an open-label, nonrandomized, multicenter phase 2 study with nine disease-specific cohorts and recorded enrollment of 329. Cohorts 1–8 study enfortumab vedotin; cohort 9 studies enfortumab vedotin with pembrolizumab. The primary endpoint is confirmed ORR by RECIST v1.1 investigator assessment in the Response Evaluable Set for cohorts 1–8, using an exact binomial confidence interval.

The registry record lists 12 outcome measures and zero analyses. It does not report the primary ORR estimate or its confidence interval, or analyses of the listed secondary outcomes. Safety counts and selected serious adverse event terms are reported for specified cohorts. Because the study is nonrandomized and cohort populations differ, these figures do not provide a randomized treatment comparison.