A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study (NCT04215146), a randomized phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

3. Trial Design

BRACELET-1 (NCT04215146) is registered as a phase 2, randomized, open-label, parallel-group study sponsored by Oncolytics Biotech. The registry lists enrollment of 48 and the condition Breast Cancer Metastatic. The study started on 2020-06-10, had a primary completion date of 2022-08-01, and is listed as active, not recruiting.

The brief summary describes an investigation in HR-positive/HER2-negative breast cancer that is locally advanced or has metastasized. Its stated treatment question is whether pelareorep with paclitaxel and avelumab is more effective than paclitaxel alone or pelareorep with paclitaxel. The registry arm descriptions identify Cohort 1 as paclitaxel alone, Cohort 2 as pelareorep plus paclitaxel, and Cohort 3 as pelareorep plus paclitaxel plus avelumab.

There is a labeling issue to keep in mind when interpreting the outcome results: the posted primary outcome groups are titled Pelareorep, Pelareorep + Paclitaxel, and Pelareorep + Paclitaxel + Avelumab. The first outcome label does not match the Cohort 1 description of paclitaxel alone. The record does not explain this discrepancy, so the outcome group names are retained when describing the numerical results rather than assuming how the labels correspond.

The primary outcome is overall response rate at week 16 according to RECIST V1.1. The registry reports a percentage of participants and an 80% confidence interval for each group. No analysis records are posted, and no secondary outcomes are posted in the record described. Details of allocation procedures, masking beyond the registry's NONE designation, and the study's original statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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: This is an open-label randomized Phase 2, 3-cohort study for patients with hormone receptor (HR)-positive (HR+)/ Human Epidermal Growth Factor Receptor 2 (HER2)-negative (HER2-), endocrine-refractory metastatic breast cancer.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate, measured over at week 16.

Overall response rate (ORR) is the primary endpoint, measured at week 16 according to RECIST V1.1. The registry expresses it as a percentage of participants. In general, ORR summarizes the proportion of an assessed group that meets a prespecified definition of tumor response. It is used in oncology studies because it provides a direct, time-specific measure of observed response rather than a measure of how long participants live or how long a response lasts. The detailed response categories and assessment procedures used in this trial are not reported in the registry record.

The posted group estimates are 20.0% for Pelareorep, with an 80% confidence interval of 7.6% to 39.3%; 31.3% for Pelareorep + Paclitaxel, with an 80% confidence interval of 16.1% to 50.4%; and 14.3% for Pelareorep + Paclitaxel + Avelumab, with an 80% confidence interval of 3.9% to 33.7%. These are estimates of response at the specified time point, not measures of response duration or overall survival. The endpoint is clinically interpretable as a response proportion, but its meaning depends on who was assessed and how response was determined. The analysis population and missing-outcome handling are not reported in the registry record.

7. Results Posted in the Registry

• Pelareorep + Paclitaxel: 31.2% (5/16) versus 20.0% (3/15) on control; risk difference 11.2 percentage points (95% CI -19.2 to 41.7), risk ratio 1.56 (0.45–5.43); unadjusted two-proportion z-test p = 0.474.
• Pelareorep + Paclitaxel + Avelumab: 11.8% (2/17) versus 20.0% (3/15) on control; risk difference -8.2 percentage points (95% CI -33.6 to 17.1), risk ratio 0.59 (0.11–3.06); unadjusted two-proportion z-test p = 0.522.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant is classified according to whether an overall response was recorded at week 16. The registry reports the percentage in each group and an 80% confidence interval. In general, a confidence interval represents uncertainty around an estimated quantity under the statistical method used. It is not a range containing a fixed proportion of individual responses, and it does not guarantee that the true value lies within its limits. The interval's width conveys precision: wider intervals indicate less precision.

What do the group percentages describe?

Each percentage is a group-level response estimate. The registry reports 20.0% for Pelareorep, 31.3% for Pelareorep + Paclitaxel, and 14.3% for Pelareorep + Paclitaxel + Avelumab. These values describe the posted response outcome for each named group at week 16, according to RECIST V1.1. They are not adjusted comparisons, and they do not account for other participant or disease characteristics. The adjustment plan, if any, is not reported in the registry record.

The listed group sizes are 15, 16, and 17, respectively. For a binary outcome, the estimate can be sensitive to the classification of individual participants when groups are small. General statistical principle: the amount of information in a percentage depends not just on its numerical value but also on the number of observations behind it. That is one reason to read each estimate alongside its confidence interval.

How should the comparisons be understood?

The posted comparisons are risk differences, comparing each combination group with the outcome group labelled Pelareorep. A risk difference is an absolute comparison between two event proportions. In general, a value of no difference is the reference point for interpreting this measure: values in one direction indicate a higher observed proportion in one group, and values in the other direction indicate a lower observed proportion. The reported comparison intervals include both directions for each contrast, so the data do not tightly determine the direction or size of a group difference.

The unadjusted p-values are 0.474 for Pelareorep + Paclitaxel and 0.522 for Pelareorep + Paclitaxel + Avelumab. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. These p-values do not provide a clear distinction between the groups. No multiplicity adjustment is reported, and the registry record does not provide the detailed testing plan, so the comparison results should be treated as unadjusted.

Other common comparative measures include relative risks and odds ratios. In general, these express a comparison on a relative rather than absolute scale. The registry contains values for those measures, but the risk-difference results and group response estimates provide the main interpretation. Relative measures can be especially unstable when event counts are small, and their confidence intervals in this record are broad. They should not be mistaken for evidence of a precise treatment effect.

What does the confidence level mean?

The registry reports 80% confidence intervals for the primary outcome estimates. In general, a confidence level describes the long-run coverage of an interval procedure under repeated use and the method's assumptions. An 80% interval is less conservative, and typically narrower, than a 95% interval constructed from the same data and method. It therefore communicates uncertainty, but it should not be interpreted as having the same coverage as the more commonly encountered 95% interval. The registry's rationale for selecting this confidence level is not reported in the registry record.

For the comparisons, the reported risk-difference intervals are also broad and cross the no-difference value. A confidence interval gives more information about plausible effect sizes than a p-value alone because it displays the range of estimates compatible with the data and method. In this study, that range is not narrow enough to support a precise conclusion about the direction of the response difference.

What is not available about the analysis?

The registry record lists no analyses and no posted secondary outcomes. It does not report an analysis population, handling of participants without an evaluable week-16 response, or whether any adjustment for covariates was planned. The original sample-size justification, interim analyses, and detailed statistical plan are also not reported in the registry record. These omissions prevent a full assessment of whether the posted outcome analysis followed a prespecified plan or how missing data may affect the estimates.

General statistical principle: randomization can support fair group comparisons when allocation is implemented as intended and outcomes are analyzed appropriately, but it does not remove uncertainty from small groups or resolve reporting gaps. The registry marks the study as randomized and unmasked; further detail about the randomization process is not reported in the registry record. The mismatch between the first cohort description and the first outcome label also needs to be borne in mind when interpreting the comparator. These issues do not change the reported percentages, but they limit the conclusions that can be drawn from them.

10. Confidence Intervals and Precision

Precision is limited for the week-16 response estimates. The 80% confidence intervals are 7.6% to 39.3% for Pelareorep, 16.1% to 50.4% for Pelareorep + Paclitaxel, and 3.9% to 33.7% for Pelareorep + Paclitaxel + Avelumab. Each interval spans a substantial range of possible response proportions. The intervals overlap, and the small group sizes contribute to uncertainty around the estimates.

The comparison intervals reinforce this uncertainty: the risk-difference interval for each combination group includes values indicating either direction of difference relative to the Pelareorep-labelled group. Thus, the point estimates alone should not be treated as precise estimates of how much the groups differ. The unadjusted p-values, 0.474 and 0.522, are also consistent with substantial uncertainty rather than a sharply resolved contrast.

In general, confidence intervals quantify sampling uncertainty under a specified method; they do not account automatically for every source of uncertainty. For example, the registry record does not report how missing week-16 outcomes were handled, so the intervals cannot resolve potential uncertainty from that issue. The 80% confidence level is another interpretive consideration: it has a different long-run coverage target from a 95% interval. The registry's reason for using 80% intervals is not reported in the registry record.

Overall, these estimates are informative as observed group summaries, but their precision is limited. A reader should give the interval ranges and reporting gaps at least as much attention as the ordering of the point estimates.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrative calculations based on the observed comparison effects, not the trial's original design assumptions. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial's own sample-size justification and original design assumptions are not reported in the registry record.

For the comparison of Pelareorep + Paclitaxel with Pelareorep, planning for 100% of the observed effect gives 236 participants per arm for 80% power and 315 participants per arm for 90% power. Planning for 75% of the observed effect gives 404 participants per arm for 80% power and 540 participants per arm for 90% power. Planning for 50% of the observed effect gives 873 participants per arm for 80% power and 1,168 participants per arm for 90% power.

For the comparison of Pelareorep + Paclitaxel + Avelumab with Pelareorep, planning for 100% of the observed effect gives 309 participants per arm for 80% power and 412 participants per arm for 90% power. Planning for 75% of the observed effect gives 578 participants per arm for 80% power and 772 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,362 participants per arm for 80% power and 1,823 participants per arm for 90% power.

In general, power is the probability that a study will detect an effect of the specified size under the planning assumptions if that effect is present. The 80% and 90% columns indicate different target probabilities, not observed properties of the completed study. These figures are participants per arm, not total participants or total events. Smaller effects need more participants to detect, which is why the figures increase when the assumed effect is reduced. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.200; treatment proportion p₁ = 0.312; average p̄ = 0.256.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6174 = 1.2101.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6122 = 0.5153.
4. n = (1.2101 + 0.5153)² / (0.1125)² = 235.2, rounded up to 236 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.2                          # control proportion
p1 <- 0.3125                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4215146)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 236 (80% power), 315 (90% power)
 75% of observed effect: n per arm = 404 (80% power), 540 (90% power)
 50% of observed effect: n per arm = 873 (80% power), 1,168 (90% power)
power.prop.test: 235.2 
Simulated power at n = 236 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record posts one primary endpoint, overall response rate at week 16, and no secondary outcomes. It contains two comparisons against the group labelled Pelareorep. The reported p-values are unadjusted, and no multiplicity procedure or testing hierarchy is reported in the registry record. When several comparisons are considered, the chance of at least one false-positive finding can increase if each is judged separately at the same threshold. General statistical principle: a prespecified testing strategy or adjustment can address that issue, but the record does not say whether one was planned.

The registry record lists no analysis records. It does not report whether the primary comparison was designated before results were examined, whether any subgroup analyses were planned, or whether the posted comparisons were the only comparisons made. Those details should not be inferred from the number of results currently listed.

Missing outcome data are another important issue for a response proportion. The registry does not report how participants without an evaluable response at week 16 were handled, whether all randomized participants were included in the analysis, or whether any imputation or sensitivity analysis was used. The analysis population is not reported in the registry record. Without these details, it is not possible to determine how incomplete outcome assessment might affect the posted estimates.

The record also does not report the original statistical plan, interim analyses, or the rationale for the 80% confidence intervals. These are not assumptions that can safely be reconstructed from the outcome results. The study is listed as randomized and unmasked, but allocation details and the procedures used to maintain or assess outcome measurement are not reported in the registry record. These gaps limit a complete evaluation of analysis choices and selective reporting, without altering the numerical results that are posted.

14. 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: febrile neutropenia (17.6%), infusion related reaction (17.6%), malaise (12.5%), pyrexia (12.5%), fatigue (11.8%).

The registry lists serious adverse event information by group. For Pelareorep, 0 of 12 participants at risk were reported with a serious adverse event, and 1 death is listed. For Pelareorep + Paclitaxel, 4 of 16 at risk were reported with a serious adverse event, and 0 deaths are listed. For Pelareorep + Paclitaxel + Avelumab, 13 of 17 at risk were reported with a serious adverse event, and 0 deaths are listed. These are the record's counts; they should not be interpreted as proof that a treatment caused or prevented an event.

The record separately lists other adverse events affecting 12 of 12, 16 of 16, and 17 of 17 participants at risk in the respective groups. The listed serious-event terms and percentages include Febrile neutropenia (17.6%), Infusion related reaction (17.6%), Malaise (12.5%), Pyrexia (12.5%), Fatigue (11.8%), and Acute respiratory distress syndrome (11.8%). The record does not identify these terms by treatment group in the information summarized, so they should not be assigned to a particular group.

In general, adverse-event counts depend on the reporting period, definitions, and participants assessed. Those details, along with causal attribution, are not reported in the registry record. Counts across groups should therefore be read descriptively, not as a complete comparative safety analysis.

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

The posted data establish the observed week-16 response proportions for the named outcome groups and show how uncertain those estimates are. The point estimate is 31.3% for Pelareorep + Paclitaxel, compared with 20.0% for Pelareorep and 14.3% for Pelareorep + Paclitaxel + Avelumab. The confidence intervals are wide, and the comparison intervals include both directions of difference. The data therefore do not precisely determine whether either combination group had a higher or lower response proportion than the group labelled Pelareorep.

The comparisons are unadjusted, with p-values of 0.474 and 0.522. These results do not establish equivalence, and they do not show that any regimen works or does not work. A non-significant comparison is not proof of no difference; it can also reflect limited information or imprecise estimates. The record does not provide a prespecified margin for equivalence or non-inferiority, so those interpretations are not supported.

The outcome is response at a single specified time point, not response duration, progression-free survival, overall survival, or quality of life. No secondary outcomes are posted in the registry record. The available primary outcome cannot answer questions about those other outcomes.

Interpretation also depends on the group labels. The arm descriptions identify Cohort 1 as paclitaxel alone, while the primary outcome uses Pelareorep as the comparator label. The record does not explain the discrepancy. Accordingly, the comparisons can be described against the outcome group called Pelareorep, but should not be confidently reframed as comparisons against paclitaxel alone without clarification.

Finally, the registry does not report the analysis population, missing-data methods, detailed statistical plan, or allocation procedures. These gaps do not erase the posted observations, but they make it harder to assess how the estimates were generated and how broadly they apply. The appropriate reading is a set of small-group response estimates with substantial uncertainty, not a definitive ranking of treatments.

16. Why This Trial Matters Statistically

This study raises several statistical issues that are common in early comparative trials. A phase 2 randomized design can produce useful estimates for planning and for deciding what questions merit further study, but its findings still require careful interpretation. Here, the group sizes are small and the response confidence intervals are broad. That combination makes point estimates particularly sensitive to a small number of outcomes and limits the precision of between-group comparisons.

The comparison scale also matters. Absolute risk differences communicate how group response proportions differ in percentage-point terms, while relative measures describe changes on a proportional scale. In this record, the comparisons are uncertain on either interpretation. The confidence intervals for the risk differences span both directions, and the unadjusted p-values do not provide a clear separation between groups. Statistical significance should not be substituted for effect size, precision, or clinical relevance.

Multiplicity and reporting transparency matter because there are multiple treatment comparisons, while no adjustment or analysis hierarchy is reported. Missing-outcome procedures and the analysis population are also not reported. Those omissions make it difficult to evaluate the full inferential process from the registry record alone.

A further issue is the mismatch between the first cohort description and the first outcome group label. The stated study question includes paclitaxel alone as a comparator, but the outcome group is labelled Pelareorep. Clarifying the correspondence would be important for readers interpreting the comparisons. Together, these features show why statistical interpretation requires attention to both numerical uncertainty and the way outcomes and groups are defined and reported.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record gives limited detail for assessing the primary outcome. It reports overall response rate at week 16 according to RECIST V1.1, but does not provide the response-category rules, assessment schedule, assessor procedures, or analysis population. Handling of missing or unevaluable week-16 assessments is also not reported. These omissions prevent a full assessment of how the percentages were derived.

The outcome groups have small listed sizes, and their 80% confidence intervals are broad. The comparison intervals include both positive and negative risk differences. The posted p-values are unadjusted; no multiplicity plan is reported. No secondary outcomes or analysis records are posted, and the original sample-size justification, interim analysis plan, and detailed statistical plan are not reported in the registry record.

The registry labels the study randomized and unmasked, but does not describe the allocation procedure. More importantly for interpretation of the posted comparison, the first arm description says paclitaxel alone while the primary outcome group is labelled Pelareorep. The record does not explain how these labels correspond. This prevents confident interpretation of that group as the paclitaxel-alone comparator stated in the brief summary.

The listed enrollment is 48, while the primary outcome reports group sizes of 15, 16, and 17. The registry does not explain the relationship between enrollment and the outcome denominators or provide a participant flow account in the information summarized. Safety results are also descriptive: causality, reporting period, and detailed event ascertainment are not reported. These limitations call for caution when generalizing the posted estimates or making comparative conclusions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study — NCT04215146.
• Registry record last updated 2025-01-16; status last verified 2025-01.
• Results first posted 2025-01-16.
• 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.

21. Record Summary

BRACELET-1 (NCT04215146) is a randomized, open-label, parallel-group phase 2 study sponsored by Oncolytics Biotech. The registry lists enrollment of 48, a start date of 2020-06-10, primary completion on 2022-08-01, and status active, not recruiting. The study concerns locally advanced or metastatic HR-positive/HER2-negative breast cancer.

The primary endpoint is overall response rate at week 16 according to RECIST V1.1. The posted response estimates are 20.0% for Pelareorep, 31.3% for Pelareorep + Paclitaxel, and 14.3% for Pelareorep + Paclitaxel + Avelumab. Each estimate has an 80% confidence interval; the intervals are broad. The two unadjusted comparison p-values are 0.474 and 0.522.

The record does not post secondary outcomes or analysis records. It does not report the analysis population, missing-data handling, multiplicity plan, or original sample-size justification. The first cohort description and first outcome group label do not align, and the registry does not explain the difference. The results are best read as imprecise response summaries rather than definitive comparative conclusions.