Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors (NCT03330405), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment.

2. Clinical Question

3. Trial Design

This was a phase 1b/2, non-randomized, unmasked, sequential study of avelumab plus talazoparib. The registry lists enrollment of 223 and describes the overall purpose as evaluating safety and anti-tumor activity in locally advanced or metastatic solid tumors. The study status is terminated. The recorded start date is 2017-10-19, and the recorded primary completion date is 2022-02-22.

The phase 1b portion had three dose-level arms: Dose Level 0, Dose Level -1, and Dose Level -2. Each listed avelumab and talazoparib. Phase 2 was divided into disease and biomarker cohorts: NSCLC, NSCLC DDR+, TNBC, hormone receptor positive breast cancer with a DDR defect and assay, recurrent platinum-sensitive ovarian cancer, recurrent platinum-sensitive ovarian cancer with BRCA defect, urothelial cancer, mCRPC, mCRPC DDR+, and advanced solid tumors with BRCA or ATM defect. These cohorts are not randomized study arms for a comparative treatment-effect estimate.

The primary outcome was a phase 2 measure. Its population description says the full analysis set included enrolled participants who received at least one dose, while the number analyzed for the outcome means those evaluable for that measure. Data for the primary outcome were not planned to be collected and analyzed for phase 1b. The registry does not report the planned allocation of participants across phase 2 cohorts, the dose-escalation decision rules, or the rationale for the enrollment target.

The study was not masked, so investigator assessment took place without masking described in the registry. Whether any independent central review was also performed is not reported in the registry record. The record lists 33 outcome measures and zero analyses. The termination reason and any changes to the study plan are not reported in the registry record, so the status alone does not explain why enrollment or follow-up ended.

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: Phase 1b: 12 participants were enrolled and assigned to study treatment. Phase 2: 211 participants were enrolled and assigned to study treatment.

Only the first 6 of 11 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT analysis set was a subset of the safety analysis set and included all enrolled participants in the Phase 1b portion who were eligible for the study, received at least 1 dose of the combination treatment, and either experienced DLT during the first cycle (28 days) of treatment, or completed the DLT observation period for the first cycle of treatment.

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.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment, measured over From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately).

The primary endpoint was the percentage of phase 2 participants with a confirmed objective response, assessed by investigators using RECIST v1.1. The outcome description excludes mCRPC participants; the primary response measure was for solid tumors other than that disease group. The stated assessment period ran from treatment start until disease progression or death from any cause, whichever occurred first, with a maximum of approximately 4.3 years.

Under the registry definition, complete response requires disappearance of target and non-target lesions, with specified normal-size requirements for nodes. Partial response requires a reduction of at least 30% from baseline in the sum of diameters of target measurable lesions, with non-target lesions not showing unequivocal progression. These criteria make response a defined tumor-assessment category rather than a general judgment that a patient improved.

Objective response is used in oncology trials to describe tumor shrinkage meeting prespecified criteria. Reporting the percentage gives a group-level summary; it does not describe how long a response lasted, whether disease was controlled without shrinking, or how outcomes compare with another treatment. Confirmation is part of the endpoint definition, but the registry does not report the numerical response estimate, its confidence interval, or the number of evaluable participants for each cohort. Those results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary participant-level primary outcome: whether a participant had a confirmed objective response under RECIST v1.1. The endpoint is then summarized as a percentage. In general, a binary outcome reduces each participant’s assessment to whether the defined event occurred or did not occur during the relevant assessment process. This makes the summary easy to interpret, but it does not preserve all details about tumor change or the time course of disease.

What does the confidence interval communicate?

The outcome’s stated dispersion measure is a 95% confidence interval. In general, a confidence interval conveys the precision of an estimate by giving a range of values compatible with the observed data under the method’s assumptions. It is not a guarantee that the true value lies in the interval, and it does not correct for biased measurement, selective reporting, or an unrepresentative study population. The registry record does not report the response estimate or its interval, so the precision of the primary result cannot be assessed.

What does confirmed response mean?

Confirmation means the primary endpoint is not simply any single investigator assessment meeting the response definition. The registry describes complete and partial response criteria based on lesion assessment under RECIST v1.1. In general, standardized response criteria make assessments more reproducible by specifying how target lesions, non-target lesions, and nodes contribute to classification. However, use of a standard criterion does not remove judgment from lesion selection or assessment. The study was unmasked and used investigator assessment; whether central review was performed is not reported in the registry record.

The stated timeframe extends from treatment start until progression or death, whichever occurred first, with a maximum of approximately 4.3 years. This is an endpoint assessment window, not a reported duration of response or a summary of how long participants remained on treatment. The registry does not provide cohort-specific follow-up summaries, the timing of response assessments, or the number of assessments contributing to confirmation. These details are not reported in the registry record.

Why does the analysis population matter?

The registry says the full analysis set included enrolled participants who received at least one dose of study treatment. It also clarifies that the number analyzed for this outcome means participants evaluable for the endpoint. Those descriptions distinguish the broad treatment-exposed analysis population from the outcome-specific evaluable group. If some treated participants were not evaluable, the percentage among evaluable participants could differ from a percentage using all treated participants as the denominator. The registry does not report the reasons for any lack of evaluability or how missing response assessments were handled.

The primary outcome was not planned for the phase 1b arm. This matters because phase 1b and phase 2 serve different roles in the record, and the primary response result should not be assumed to include phase 1b participants. The phase 2 endpoint also excludes mCRPC in its description. The registry therefore defines a population narrower than all enrolled participants, but the actual cohort-specific denominators are not reported in the registry record.

What can be inferred from a non-randomized design?

In general, random allocation helps make comparison groups similar, on average, with respect to measured and unmeasured baseline characteristics. This study is explicitly non-randomized and does not list a like-for-like control arm. As a result, its design can describe outcomes under the combination in the enrolled cohorts but cannot, by itself, isolate what would have happened under an alternative treatment. The sequential structure and different tumor cohorts also mean that one should not treat all groups as interchangeable.

The record lists no analyses. It does not describe the statistical method used to calculate the confidence interval, any hypothesis tests, adjustment for covariates, or handling of repeated assessments. These analytic details are not reported in the registry record. They should not be inferred from the endpoint’s use of RECIST or from the phase designation.

How should the safety summaries be read?

The registry gives group-level counts for serious events, other events, and deaths. In general, a count describes how many participants in a recorded group experienced the event category; it is not a rate unless the denominator and observation period are considered. Follow-up time can differ among participants, and event counts can include multiple event types or repeated episodes depending on the reporting convention. The registry does not describe all counting conventions or exposure-adjusted rates. The serious-event terms and percentages are descriptive listings, not estimates from a randomized safety comparison.

The study includes several secondary safety outcomes, including treatment-emergent events, grade >=3 events, serious events, treatment discontinuations, deaths, and hematology laboratory changes. The registry’s endpoint names indicate what was intended to be counted, but detailed analysis rules, attribution procedures, and missing-data methods are not reported in the registry record.

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("Phase 2: Cohort A1 (NSCLC)", "Phase 2: Cohort A2 (NSCLC DDR+)", "Phase 2: Cohort B1 (TNBC)", "Phase 2: Cohort B2 (BC HR+ HER2- DDR+)", "Phase 2: Cohort C1 (OVC)", "Phase 2: Cohort C2 (OVC BRCA-mutated)")
n      <- c(42, 5, 22, 23, 20, 11)
events <- c(7, 1, 4, 8, 4, 7)
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  Phase 2: Cohort A1 (NSCLC)  42  7  16.7  7.0  31.4  8.3  30.6  8.4  30.7
ARM  Phase 2: Cohort A2 (NSCLC DDR+)  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Phase 2: Cohort B1 (TNBC)  22  4  18.2  5.2  40.3  7.3  38.5  7.5  38.8
ARM  Phase 2: Cohort B2 (BC HR+ HER2- DDR+)  23  8  34.8  16.4  57.3  18.8  55.1  18.8  55.3
ARM  Phase 2: Cohort C1 (OVC)  20  4  20.0  5.7  43.7  8.1  41.6  8.2  41.9
ARM  Phase 2: Cohort C2 (OVC BRCA-mutated)  11  7  63.6  30.8  89.1  35.4  84.8  34.9  84.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 33 outcome measures, but reports zero analyses. The primary endpoint is identified, yet the record does not report a statistical analysis plan describing how multiple outcomes or multiple phase 2 cohorts were handled. Adjustment for multiplicity, a hierarchy of testing, or a prespecified approach to interpreting several cohort-specific results is not reported in the registry record.

This matters because multiple outcomes or subgroup analyses can create many opportunities to observe apparently notable findings by chance. In general, multiplicity procedures control or describe the consequences of making several statistical comparisons. Without a documented procedure and the numerical analyses, readers cannot determine whether any reported inference was adjusted for multiple testing. No claim about adjusted or unadjusted significance can be made from this record.

For the primary outcome, the registry defines the full analysis set as enrolled participants who received at least one dose, while the outcome-specific number analyzed refers to participants evaluable for the measure. The record does not report how many were evaluable in each cohort, how missing tumor assessments were handled, or whether participants without an evaluable assessment were counted as nonresponders. Imputation methods and sensitivity analyses are not reported in the registry record.

The primary endpoint was not planned for the phase 1b arm, and the endpoint description excludes mCRPC participants. These are stated population boundaries, not missing-data rules. The registry does not explain whether all planned phase 2 cohorts completed follow-up or whether any outcome populations changed during the study. The termination reason is also not reported in the registry record. Therefore, the effect of incomplete follow-up or any deviations from the planned analysis population cannot be assessed.

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: thrombocytopenia (22.2%), disease progression (22.2%), testicular pain (20.0%), haematoma (20.0%), anaemia (13.6%).

The registry reports serious adverse-event counts by study group, alongside counts for other adverse events and deaths. For example, the phase 1b group lists 12 participants at risk for serious events and 1 affected; phase 2 Cohort A1 lists 42 at risk and 16 affected. These are group-level counts, not evidence of comparative safety, because the study was non-randomized and did not include a like-for-like control group.

The registry’s listed serious-event terms include thrombocytopenia at 22.2%, disease progression at 22.2%, testicular pain at 20.0%, haematoma at 20.0%, anaemia at 13.6%, and colitis at 11.1%. These are reported as terms with percentages; the registry record does not provide enough detail in this summary to interpret them as risks over a common follow-up period. Disease progression is also a reminder that an event recorded during a cancer trial is not necessarily caused by study treatment.

Deaths are listed by group, but the registry does not identify cause in these figures. They should not be interpreted as treatment-related deaths. The counts also do not describe when events occurred or whether the same participant experienced more than one event category. Attribution details and exposure-adjusted safety rates are not reported in the registry record.

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

The record establishes that the study evaluated avelumab plus talazoparib in locally advanced or metastatic solid tumors through a sequential phase 1b/2 design. It also defines the primary phase 2 endpoint as confirmed investigator-assessed objective response under RECIST v1.1 for solid tumors except mCRPC. The record contains selected safety counts and a list of serious-event terms.

It does not report the numerical result for the primary endpoint. Accordingly, it does not show what percentage of evaluable phase 2 participants had a confirmed response, how much uncertainty surrounded that estimate, or how response differed among cohorts. Those results are not reported in the registry record. The endpoint definition alone cannot establish that a response occurred in any particular proportion.

The study’s non-randomized design also limits comparative interpretation. Without a randomized control group, an observed response percentage would describe participants treated in this study, not establish how outcomes would differ under another treatment. Differences between the disease-specific cohorts would not constitute randomized comparisons, since the groups represent different tumor types or biomarker-defined populations.

The listed safety results describe recorded events in study groups. They do not establish that an event was caused by either study drug, and deaths in the group summaries cannot be assumed to be treatment-related. The record does not provide a complete account of event timing, duration, recurrence, or attribution in the information summarized.

Thus, the registry supports understanding of the study question, its endpoint definitions, and some descriptive safety information. It does not support a numerical conclusion about primary response or a causal comparison of the combination with another treatment. A missing registry result should not be mistaken for a negative result; it is an unreported result.

14. Why This Trial Matters Statistically

This study raises a statistical challenge common to early and mid-stage oncology research: evaluating a treatment combination across several biologically and clinically different tumor groups. A response endpoint can provide a structured summary of tumor shrinkage, but separate cohorts may have different baseline characteristics and disease courses. Their results are not automatically suitable for pooling or direct comparison.

The non-randomized design is important to interpretation. It may describe outcomes among treated participants, but it does not create a randomized counterfactual for what would have happened under another treatment. Even a precise estimate would not, on its own, remove confounding or establish a causal treatment effect. The absence of the primary numerical result in the registry record makes this issue especially concrete: the design and question are described, but the principal response estimate cannot be assessed.

The record also illustrates why analysis populations and endpoint definitions need to be read together. The primary measure was not planned for phase 1b, excludes mCRPC in its description, and counts participants evaluable for the outcome. Those details define who contributes to the endpoint and prevent the overall enrollment figure from being mistaken for the primary-outcome denominator.

Finally, safety summaries require both event counts and context. Serious-event terms can include disease-related events as well as events potentially associated with treatment. Without a randomized comparator, consistent exposure-time summaries, and attribution details, raw counts are descriptive rather than comparative evidence. The registry’s available information therefore helps explain what was studied, while leaving key questions about the observed response and its statistical precision unresolved.

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 trial-specific limitations affect what can be concluded from the registry record. The study was non-randomized and unmasked, with no like-for-like control comparison. Investigator assessment was used for the primary response endpoint; whether an independent central review supplemented it is not reported in the registry record. Differences across tumor cohorts should not be interpreted as treatment contrasts because cohorts were defined by cancer type or biomarker status.

The main limitation for interpreting efficacy is that the numerical primary response results and confidence intervals are not reported in the registry record. Cohort-specific denominators and response counts are also not reported. The primary outcome was not planned for phase 1b, and mCRPC participants were excluded from the primary endpoint description. Therefore, the overall enrollment figure does not supply the outcome denominator.

The record lists 33 outcome measures and zero analyses. Statistical methods for the primary confidence interval, multiplicity handling, missing response assessments, and any sensitivity analyses are not reported in the registry record. This prevents assessment of how uncertainty, multiple outcomes, or incomplete assessment may have affected the reported conclusions.

The study is marked terminated, but the reason for termination and any effect on cohort completion or follow-up are not reported in the registry record. Safety summaries include event counts and selected serious-event terms, but do not establish treatment attribution or provide a common follow-up basis in the information summarized. The registry record therefore offers limited support for conclusions about comparative efficacy, precision, or causal safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors — NCT03330405.
• Registry record last updated 2023-10-13; status last verified 2023-10.
• Results first posted 2023-06-12.
• 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

JAVELIN PARP Medley (NCT03330405) was a non-randomized, unmasked, sequential phase 1b/2 study of avelumab plus talazoparib in locally advanced or metastatic solid tumors. The registry lists enrollment of 223, status as terminated, a start date of 2017-10-19, and primary completion on 2022-02-22.

The primary phase 2 endpoint was confirmed objective response by investigator assessment using RECIST v1.1, for solid tumors except mCRPC. The registry record does not report the numerical primary response result or its confidence interval. It lists 33 outcome measures and zero analyses, and includes group-level adverse-event counts and serious-event terms. The non-randomized design does not provide a like-for-like control comparison, and the reason for termination is not reported in the registry record.