A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF) (NCT03472560), a na phase 2 study. The primary outcome is Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, single-group study of avelumab combined with axitinib. The record lists an enrollment of 61 and identifies two cancer populations: participants with advanced or metastatic NSCLC after at least one prior platinum-containing therapy, and treatment-naïve participants with advanced or metastatic urothelial cancer who were ineligible for cisplatin-containing chemotherapy for their advanced disease.

The regimen was avelumab 800 mg intravenously every two weeks with axitinib 5 mg orally twice daily. Because the design was single-group and allocation is listed as not applicable, the study does not provide a randomized comparison against another treatment or a control group. The two cancer groups differ in disease type and treatment history, so their results should not be treated as a direct comparison of therapies or as interchangeable populations.

The study began on 2018-05-02, had a primary completion date of 2023-02-09, and is listed as terminated. The reason for termination is not reported in the registry record. The record identifies safety and clinical activity as the study aims, but does not report a detailed statistical analysis plan, the reason for the enrollment target, or whether interim analyses were planned.

Open-label means that treatment assignment was not masked. Response was assessed by investigators, so the record does not describe a blinded response assessment. The registry record does not report additional procedures that would establish whether assessment was independently reviewed.

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: A total of 104 participants were screened, out of which 43 participants failed screening and 61 participants were enrolled into the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included all participants who received at least one dose of avelumab and axitinib. Participants were classified according to the study treatment received.

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 included all participants who received at least one dose of avelumab and axitinib.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR), measured over Baseline up to 56 months.

The primary endpoint was the percentage of participants with a confirmed objective response: a complete response or partial response assessed by the investigator according to RECIST version 1.1. The timeframe was baseline up to 56 months. A response had to be confirmed by a repeat assessment performed no less than 4 weeks after the response criteria were first met.

Under the recorded criteria, a complete response required disappearance of target lesions and non-target disease, with the stated exception for nodal disease; all nodes had to decrease to normal size, and there could be no new lesions. A partial response required at least a 30% decrease from baseline in the sum of diameters of target lesions, with no unequivocal progression of non-target disease and no new lesions. Stable disease meant that the criteria for complete response, partial response, or progressive disease were not met.

As a general statistical concept, objective response rate is a binary outcome at the participant level: each participant either meets the confirmed-response definition or does not. It offers a defined way to describe tumor shrinkage meeting prespecified criteria, but it does not by itself describe how long a response lasts, time to progression, or survival. The registry lists those as separate secondary outcomes. A numerical primary endpoint result and its confidence interval are not reported in the registry record, so the response rate and its precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow?

As a general statistical concept, a single-group study describes outcomes among participants who receive the study regimen. It does not include a randomized control group against which to estimate a comparative treatment effect. In this study, the record lists avelumab plus axitinib as the regimen and identifies separate NSCLC and urothelial cancer populations. Those populations are not interchangeable controls: their cancer types and eligibility histories differ.

The open-label design means treatment was not masked. The primary endpoint was based on investigator assessment, and the registry record does not report whether an independent blinded review was also conducted. In general, knowledge of treatment can be relevant when outcomes require judgment, which is one reason the assessment process is important to understand. The record specifies RECIST version 1.1 and confirmation by repeat assessment, but does not provide further details of response review.

What does the response endpoint count?

As a general statistical concept, a binary endpoint classifies each participant into one of two outcome categories. Here, confirmed complete response or partial response counted as an objective response; the endpoint was the percentage of participants meeting that definition. The criteria set out what tumor changes qualified and required a repeat assessment no less than 4 weeks after response criteria were first met. This confirmation requirement distinguishes a confirmed response from a single assessment meeting response criteria.

A percentage is informative only when its denominator and outcome count are clear. The registry defines the Full Analysis Set as participants who received at least one dose of both drugs and were classified according to treatment received. However, the numerical primary result and the disease-specific analysis denominators are not reported in the registry record. No response percentage should therefore be inferred from the enrollment count or from safety counts.

How should a confidence interval be understood?

As a general statistical concept, a confidence interval expresses the uncertainty associated with an estimated quantity. For a response percentage, it would indicate a range of values compatible with the data under the method used. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry identifies a 95% confidence interval for the primary outcome, but does not report its numerical limits or the response estimate. Consequently, neither the size of the estimated response nor its precision can be assessed from the record.

A confidence interval is not a guarantee that the true value lies within a particular range, and it does not address every source of uncertainty. In a single-group study, an interval around a response percentage would describe uncertainty in that group’s estimate; it would not create a randomized comparison or resolve differences between the study population and other populations.

Why do analysis populations matter?

As a general statistical concept, the analysis population determines which participants contribute to an endpoint estimate. The record’s primary population includes participants who received at least one dose of both study drugs. That definition helps specify who is eligible for the endpoint analysis, but the registry record does not provide the population count used for the primary result or explain how missing response assessments were handled. Enrollment and the safety groups’ at-risk counts should not be assumed to equal the primary analysis denominator.

The study has two disease-specific groups. Reporting an overall result across both groups, if one were available, would require care because the participants differ by cancer type and eligibility history. The registry record does not give a primary response estimate for either group or a combined estimate, so neither can be reconstructed from the reported information.

What can the planning illustrations tell readers?

As a general statistical concept, sample-size calculations depend on assumptions about the effect to detect, the significance level, allocation, and statistical method. The planning illustrations associated with this analysis use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the assumed effect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the stated method uses a total event count based on Schoenfeld; other calculations are expressed as participants per arm.

These are planning illustrations, not the study’s observed power and not a report of the trial’s own design justification. The record does not report the protocol’s sample-size justification, and the study itself is listed as single-group rather than as a two-arm randomized comparison. Any two-arm illustration should therefore be read as a hypothetical planning exercise, not as a description of the trial’s allocation. No planning count can supply a missing primary outcome or establish how much information the study actually obtained.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a method assumes less variability than the data contain, uncertainty can be understated and statistical conclusions can appear more precise than warranted. The primary endpoint in this study is a participant-level response percentage, and the registry record does not report an over-dispersion analysis or a model for the primary endpoint. This general issue should not be mistaken for a documented feature of this study’s analysis.

More broadly, statistical methods cannot compensate for missing outcome reporting. The registry record gives the endpoint definition and a confidence-interval specification, but does not report the estimate, interval limits, or a detailed analysis plan. Interpretation must therefore remain limited to the design and definitions that are recorded.

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("NSCLC Avelumab + Axitinib", "UC Avelumab + Axitinib")
n      <- c(41, 20)
events <- c(13, 2)
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  NSCLC Avelumab + Axitinib  41  13  31.7  18.1  48.1  19.6  47.0  19.6  47.1
ARM  UC Avelumab + Axitinib  20  2  10.0  1.2  31.7  2.8  30.1  3.0  30.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including the primary response endpoint and secondary measures such as adverse events, laboratory results, time to tumor response, duration of response, progression-free survival, overall survival, and maximum observed serum concentration of avelumab. Considering multiple outcomes can raise a general statistical issue: when many questions are tested, the chance of at least one apparently noteworthy finding can increase. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a detailed statistical plan. It is therefore not possible to determine how multiplicity was addressed.

The record lists zero analyses. This means no analyses are listed in the registry record; it does not provide a numerical primary result. The reason for study termination and whether any interim analyses were planned or conducted are not reported in the registry record.

The primary analysis population is defined as participants who received at least one dose of avelumab and axitinib. The record does not report the number included in the primary endpoint analysis, the number with missing response assessments, or the method used to handle missing data. As a general statistical principle, missing outcome information can affect both the denominator and interpretation of a percentage, depending on how it is handled. No particular missing-data method should be assumed.

The safety summaries identify participants at risk for the adverse-event categories, but these counts do not establish the primary endpoint denominator. The registry record also does not report whether all planned outcome data were collected or why the study was terminated. These omissions restrict assessment of completeness and analysis 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: disease progression (15.0%), haematuria (10.0%), pyrexia (7.3%), fatigue (5.0%), colitis (5.0%).

The safety record separates participants with NSCLC from those with urothelial cancer. In the NSCLC group, 41 participants were listed as at risk for serious adverse events and 21 as affected; 41 were listed as at risk for other adverse events and 41 as affected. In the urothelial cancer group, 20 participants were listed as at risk for serious adverse events and 11 as affected; 20 were listed as at risk for other adverse events and 17 as affected. The record lists 27 deaths in the NSCLC group and 11 in the urothelial cancer group.

The listed serious adverse-event terms and percentages are disease progression, 15.0%; haematuria, 10.0%; pyrexia, 7.3%; fatigue, 5.0%; colitis, 5.0%; and dysphagia, 5.0%. These are the terms identified among the top serious adverse events; the registry record does not provide further context about each term’s timing, relationship to treatment, or severity distribution.

As a general statistical principle, counts and percentages describe different aspects of safety reporting. A count indicates how many participants were recorded, while interpretation of a percentage depends on its denominator and the event definition. The listed figures do not by themselves establish causation, comparative risk, or a treatment effect. The study has no randomized control group, and the reason for termination is not reported in the registry record.

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

The record establishes the study question and the way the primary endpoint was defined: the percentage of participants with a confirmed complete or partial response by investigator assessment under RECIST version 1.1. It also records the treatment regimen, the two disease populations, the study’s single-group open-label design, and selected safety counts. It does not report a numerical primary response result or its 95% confidence interval.

Accordingly, the posted information does not show the observed response percentage, how precisely it was estimated, or how the result differed between the NSCLC and urothelial cancer groups. It also does not provide numerical results for the listed secondary outcomes. The absence of these values should not be interpreted as a zero response, a negative finding, or evidence that an outcome was not measured; the registry record simply does not report those results.

Even if a response estimate were available, a single-group study would describe outcomes in the treated participants rather than provide a randomized estimate of benefit relative to a control. The two disease groups differ in cancer type and treatment history, so they cannot serve as each other’s control. The open-label design and investigator-assessed response are relevant features to consider when interpreting any reported result.

The safety counts provide descriptive information for the groups at risk, but they do not establish that the study drugs caused each event or death. The record does not report a comparative safety analysis. The listed status is terminated, but the reason for termination is not reported in the registry record, so that status cannot be used to infer the study’s clinical findings or the reason for its ending.

Overall, the registry record supports a description of the trial’s design, endpoint definitions, and selected safety reporting. It does not support a conclusion about the magnitude, precision, or comparative effect of the regimen on objective response.

14. Why This Trial Matters Statistically

This study raises several important statistical interpretation issues. First, it evaluates two clinically distinct populations within one study record: previously treated NSCLC and treatment-naïve, cisplatin-ineligible urothelial cancer. Their eligibility histories and disease types differ, so combining or comparing their outcomes would require clear justification and disease-specific reporting. The registry record does not report numerical primary response results for either group.

Second, the single-group, open-label design frames the kind of inference available. A response rate could describe the observed outcome in the treated population, but without random allocation to a comparator it would not provide a randomized estimate of comparative treatment effect. Investigator assessment also makes the stated assessment process relevant to interpretation; the registry identifies RECIST version 1.1 and response confirmation, but does not report whether a separate blinded review was used.

Third, the registry record illustrates the difference between defining an endpoint and reporting its result. It provides a detailed objective-response definition and a confidence-interval specification, but no response estimate or interval limits. Without those results, readers cannot judge the observed response frequency or its precision. The listed secondary outcomes and safety terms likewise should not be mistaken for complete outcome reporting.

Finally, study status and enrollment do not resolve these statistical questions. The record lists enrollment of 61 and a terminated status, but does not report the reason for termination, the primary analysis denominator, or the handling of missing response assessments. These details matter because they affect how complete and representative an endpoint estimate may be. The available information therefore supports careful description of design and reporting, not a comparative efficacy conclusion.

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 registry record contains no numerical result for the primary objective response endpoint, despite specifying its definition, assessment method, timeframe, and 95% confidence interval. It also does not report numerical results for the secondary outcomes listed, including progression-free survival, overall survival, duration of response, and time to tumor response. As a result, the clinical activity outcomes cannot be evaluated from the posted information.

The primary analysis population is defined, but its size and the number of participants with evaluable response assessments are not reported. The handling of missing response data is also not reported in the registry record. Although the record lists enrollment of 61, that figure cannot be assumed to equal the primary analysis denominator or the number with complete endpoint data.

The single-group, open-label design has no randomized control comparison. The registry record does not report whether response assessments received independent review. It also does not report a detailed statistical analysis plan, multiplicity procedures, interim analyses, or the protocol’s sample-size justification. The reason for termination is not reported in the registry record.

The two disease groups have different cancer types and treatment histories; findings from one group would not automatically apply to the other. The serious adverse-event summaries are descriptive and do not provide a randomized safety comparison or establish causation. The record does not report additional context needed to assess the timing and treatment relationship of each listed event. These limitations are specific to the recorded design and reporting and should be kept separate from any conclusions drawn from data not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF) — NCT03472560.
• Registry record last updated 2024-04-09; status last verified 2024-03.
• Results first posted 2024-04-09.
• 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 record describes NCT03472560, a Phase 2, open-label, single-group study sponsored by Pfizer. It evaluated avelumab with axitinib in advanced or metastatic NSCLC after at least one prior platinum-containing therapy, and in treatment-naïve advanced or metastatic urothelial cancer when participants were ineligible for cisplatin-containing chemotherapy. The recorded regimen was avelumab 800 mg intravenously every two weeks with axitinib 5 mg orally twice daily.

The primary endpoint was the percentage with confirmed objective response by investigator assessment under RECIST version 1.1, from baseline up to 56 months. The record lists enrollment of 61, a start date of 2018-05-02, a primary completion date of 2023-02-09, and terminated status. The reason for termination is not reported in the registry record. A numerical primary response result, its confidence interval, and the listed secondary outcome results are not reported in the registry record.