A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer (NCT04505826), a non-randomized phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicities (DLT).

2. Clinical Question

The study was designed to examine safety and pharmacokinetics across OP-1250 doses, identify a maximum tolerated dose and/or recommended Phase II dose, and confirm the recommended dose during expansion. The Phase II portion further explores clinical activity, safety, and pharmacokinetics of monotherapy at the recommended dose, with preliminary anti-tumor efficacy to be estimated in three cohorts.

This is a dose-finding and early clinical-activity study, not a randomized comparison of OP-1250 against another treatment. The registry describes the Phase II cohorts in part, including a cohort with measurable disease and no evidence of central nervous system metastases; the complete cohort descriptions are not reported in the registry record. The primary endpoint is specifically limited to the escalation phase. A numerical count of participants with dose-limiting toxicities is not reported in the registry record, so the central endpoint question cannot be answered from the recorded results.

3. Trial Design

This completed study combined Phase I dose escalation and dose expansion with Phase II monotherapy evaluation. Its official description identifies it as an open-label, first-in-human, multicenter study. The registry records non-randomized allocation, no masking, and a sequential model. Enrollment is recorded as 153. The study start date is 2020-08-13, and the primary completion date is 2024-07-30.

In Phase I Part A, the study evaluated safety and pharmacokinetics across a range of OP-1250 doses, with the stated aim of identifying the maximum tolerated dose and/or recommended Phase II dose. Phase I Part B evaluated safety and pharmacokinetics to confirm the recommended dose. The Phase II portion explored clinical activity, safety, and pharmacokinetics of OP-1250 monotherapy at that dose, and aimed to estimate preliminary anti-tumor efficacy in three cohorts. The study description identifies dose groups including 30 mg QD, 60 mg QD, 90 mg QD, 120 mg QD, 150 mg QD, 210 mg QD, and 300 mg QD; a separate group is labeled 120 mg QD (COHORT C ONLY).

Because participants were not randomly allocated to treatment groups and there was no masking, observed differences between dose groups would not establish comparative treatment effects. Group membership may reflect the sequential dose-finding design and cohort-specific enrollment. The registry does not report the allocation details beyond non-randomized status, the dose-escalation decision rules, or the full rationale for assigning participants to each cohort. Those design features should not be inferred from the group labels alone.

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.

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: Per the protocol DLTs were evaluated at Escalation phase (1a) only

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 Dose Limiting Toxicities (DLT), measured over Up to 28 days from start of treatment.

The primary endpoint is the number of participants with dose-limiting toxicities during dose escalation only. The registry defines the observation period as up to 28 days from the start of treatment and states that dose-limiting toxicities were evaluated during the escalation phase, identified as Phase I Part A. The measure is a participant count, rather than a measure of how many separate events each participant experienced.

Dose-limiting toxicity is used in early dose-finding research to identify tolerability concerns that may constrain dose selection. In this study, the Phase I Part A description links dose escalation with identifying a maximum tolerated dose and/or recommended Phase II dose. The endpoint therefore addresses a specific early safety question over a defined observation window; it is not, by itself, a complete account of all safety outcomes throughout treatment or a measure of anti-tumor activity.

The registry record does not report the numerical primary endpoint result, a denominator for the endpoint population, or further operational details defining which events counted as dose limiting. The posted adverse-event figures are not a substitute for the primary endpoint: they cover serious and other adverse events by listed dose group and do not identify which events met the protocol definition of a dose-limiting toxicity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods should be read in light of the study’s early-phase, sequential, non-randomized design. The primary outcome is a participant count for dose-limiting toxicities during Phase I Part A, with assessment up to 28 days from treatment start. The posted adverse-event figures are also counts. No inferential analyses are reported in the registry record, so there are no posted estimates, confidence intervals, or hypothesis tests to interpret for the primary endpoint.

What does a participant count represent?

A count records how many people in a defined group experienced an outcome. It is distinct from an event count, because a participant may experience more than one event. For the primary endpoint, the registry explicitly describes the measure as the number of participants with dose-limiting toxicities. A count is most interpretable alongside a clearly defined analysis population and denominator. The record describes the primary endpoint population as the escalation phase only, but a numerical endpoint result and its denominator are not reported in the registry record.

Similarly, the serious adverse-event summaries identify participants at risk and participants affected within each named group. Those figures describe the recorded groups; they do not automatically estimate a causal effect of dose. The study was non-randomized and sequential, so participants at different dose levels need not be comparable in all relevant respects. The recorded group sizes also vary. A larger affected count in a group may reflect a larger group as well as differences in event experience, and the raw counts do not adjust for differences in group composition or time under observation.

Why does the design matter for comparisons?

Randomization is used in comparative trials to make treatment assignment independent of participants’ measured and unmeasured characteristics, on average. This trial’s allocation is recorded as non-randomized, with a sequential model and no masking. Accordingly, dose groups are not equivalent to randomized treatment arms. The doses were studied as part of dose escalation and expansion, and the registry describes the later Phase II work as evaluating monotherapy at the recommended Phase II dose. A contrast between dose groups could therefore mix dose differences with differences in when or why participants entered a group.

Open-label status means that treatment assignment was not masked. The registry does not report whether endpoint assessment involved any additional safeguards, nor does it describe adjudication procedures. These details should not be assumed. For a toxicity endpoint, event recognition and classification depend on the study’s definitions and assessment procedures; complete operational criteria are not reported in the registry record.

How should confidence intervals and tests be understood?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under specified assumptions. It helps distinguish a precise estimate from one that remains compatible with a broad range of values. A hypothesis test evaluates how compatible observed data are with a specified null model; a p-value is not a measure of clinical importance or the probability that a hypothesis is true. These concepts are general statistical explanations, not reported results from this study. No confidence interval, p-value, or statistical test for the primary outcome is reported in the registry record, so none can be used to quantify the endpoint’s uncertainty.

Counts can be summarized without an inferential model, but statistical interpretation ordinarily depends on knowing the intended population, outcome definition, missing-data handling, and analysis plan. Those details are not fully available for the primary endpoint. In particular, the record does not report how participants without a complete assessment in the endpoint window would be handled, or whether any protocol deviations changed endpoint classification.

What do the planning assumptions mean?

The stated sample-size planning illustration is based on the observed effect, uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These are assumptions for a planning illustration, not the documented design justification for this study. The registry does not report that these assumptions governed enrollment or that a randomized two-arm comparison was conducted. Sample-size planning values are not observed evidence and should not be interpreted as observed power. The record does not report the trial’s own sample-size justification.

In general, a planning calculation estimates how much information a future design might need under stated assumptions. Such a calculation depends on the assumed effect, variability or event rate, significance threshold, allocation, and analysis method. If those assumptions differ from a future study, its operating characteristics may differ as well. The listed planning framework does not convert this non-randomized dose study into a controlled comparison, nor does it supply a missing primary endpoint result.

Why can adverse-event summaries be incomplete for dose decisions?

Safety interpretation can require more than whether an event was classified as serious. Event severity, timing, duration, recurrence, attribution, and relationship to dose may all matter, as may the period during which participants were observed. General statistical practice treats these as distinct features rather than assuming that one count captures the full safety profile. The record reports serious-event counts, other-event counts, and deaths by group, but those summaries do not establish causation or provide the full context of each event. The reported dose-limiting toxicity endpoint is also narrower than an all-period safety assessment because it applies to escalation only and has a specified assessment window.

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("30 mg QD (Phase 1a)", "60 mg QD (Phase 1a)", "90 mg QD (Phase 1a)", "120 mg QD (Phase 1a)", "150 mg QD (Phase 1a)", "210 mg QD (Phase 1a)")
n      <- c(5, 6, 6, 6, 5, 7)
events <- c(0, 0, 0, 0, 0, 0)
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  30 mg QD (Phase 1a)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  60 mg QD (Phase 1a)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  90 mg QD (Phase 1a)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  120 mg QD (Phase 1a)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  150 mg QD (Phase 1a)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  210 mg QD (Phase 1a)  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan describing how inference across outcomes, cohorts, dose groups, or repeated analyses was controlled. Without that information, it is not possible to determine whether any statistical adjustment was planned or whether outcomes were designated as confirmatory versus exploratory beyond the descriptions recorded. The Phase II portion is described as exploring clinical activity, safety, and pharmacokinetics and estimating preliminary anti-tumor efficacy in three cohorts; numerical efficacy results and analysis details are not reported in the registry record.

Missing-data methods are not reported in the registry record. For the primary endpoint, the stated assessment period is up to 28 days from treatment start, but the record does not explain how participants with incomplete follow-up, early discontinuation, or missing toxicity assessments would be treated in the analysis. It also does not report whether the endpoint denominator includes all participants who started escalation or another defined population. Without these details, the count cannot be fully interpreted as a rate or as an estimate for a clearly specified population.

Analysis populations are not described beyond the statement that dose-limiting toxicities were evaluated during the escalation phase only. The record does not report which participants were included in pharmacokinetic, safety, or Phase II efficacy analyses, or how exclusions and protocol deviations were handled. These omissions limit reproducibility and make it difficult to judge whether the reported adverse-event denominators align with the primary endpoint population. The absence of reported methods does not establish that no procedures were used; it means those procedures are not reported in the registry record.

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: fall (28.6%), bronchitis (20.0%), febrile neutropenia (20.0%), covid-19 (16.7%), bone pain (16.7%).

The serious adverse-event figures are counts of participants affected and participants at risk within each listed dose group. The registry reports 0 of 5 at 30 mg QD, 4 of 33 at 60 mg QD, 2 of 6 at 90 mg QD, 16 of 83 at 120 mg QD, 2 of 5 at 150 mg QD, 2 of 7 at 210 mg QD, 2 of 7 at 300 mg QD, and 4 of 7 at 120 mg QD (COHORT C ONLY). These are descriptive group-specific observations, not randomized comparisons.

Listed serious event terms include Fall at 28.6%, Bronchitis at 20.0%, Febrile neutropenia at 20.0%, COVID-19 at 16.7%, Bone pain at 16.7%, and Bacteraemia at 14.3%. The registry summary does not provide enough detail to establish the denominator or overlap among these term percentages; participants may also have experienced more than one event. The percentages should therefore be read as reported, without treating them as mutually exclusive categories or adding them together.

Deaths are listed by dose group, but the registry figures alone do not establish cause or relationship to treatment. Serious-event counts are also not equivalent to the primary dose-limiting toxicity outcome, which applies only to dose escalation and has a distinct assessment window and definition.

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

The study addresses early evaluation of oral OP-1250 as monotherapy in adults with advanced and/or metastatic HR-positive, HER2-negative breast cancer. Its design combines dose escalation, dose expansion, and Phase II exploration. The registry describes the purposes of these stages: examining safety and pharmacokinetics, identifying and confirming a recommended dose, and exploring clinical activity and preliminary anti-tumor efficacy.

The posted safety figures document serious adverse events, other adverse events, and deaths in named dose groups. They provide descriptive information about what was recorded among participants at risk in those groups. Because the design is non-randomized and sequential, these observations do not establish that one dose is safer or less safe than another. Nor do the listed deaths, without causal attribution, show that OP-1250 caused them. The summaries also do not replace the protocol-defined dose-limiting toxicity endpoint.

The primary endpoint is the number of participants with dose-limiting toxicities during escalation, assessed up to 28 days from treatment start. Its numerical result is not reported in the registry record. No analyses are reported, and the record does not give inferential estimates or uncertainty intervals for the primary outcome. As a result, the available information does not permit a quantitative assessment of the primary endpoint or the precision of an estimate.

The registry descriptions of Phase II objectives are not themselves efficacy results. Numerical results for clinical activity or preliminary anti-tumor efficacy are not reported in the registry record. It is therefore not possible to draw conclusions about those outcomes from the study description or safety counts. The appropriate interpretation is limited to the design and recorded descriptive safety information, with the primary endpoint and key analysis details unavailable in the record.

14. Why This Trial Matters Statistically

This trial illustrates why dose-finding studies need to be interpreted differently from randomized comparative trials. Its sequential, non-randomized design is suited to evaluating successive doses and informing dose selection, as reflected in the stated goals of identifying a maximum tolerated dose and/or recommended Phase II dose and then confirming the recommended dose. That purpose differs from estimating a treatment effect against a randomized control group.

It also highlights the importance of matching a safety statistic to its definition. The primary endpoint concerns participants with dose-limiting toxicities during escalation, within a stated assessment period. Serious adverse-event summaries cover a separate safety category and are reported across listed dose groups. Treating the two as interchangeable would obscure what each measure captures. Likewise, a count of participants affected is not a count of every event, and group-level counts do not by themselves answer questions about event timing, duration, or attribution.

For biostatistical reporting, a numerical endpoint result and a clear denominator are central to assessing what was observed. Without the primary endpoint count, analysis population, missing-data approach, and uncertainty estimate, readers cannot evaluate the endpoint’s magnitude or precision. The absence of posted analyses also leaves no basis for interpreting statistical tests or adjusted estimates. The record’s safety figures remain useful as descriptive observations, but they cannot substitute for those missing elements or support a controlled dose comparison.

Finally, the study’s stated Phase II objectives and the posted results must be kept distinct. An objective to explore activity or estimate preliminary efficacy does not establish what the study found. Clear separation of planned questions, observed results, and statistical uncertainty is essential when communicating evidence from early-phase studies.

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 most direct limitation is that a numerical result for the primary dose-limiting toxicity endpoint is not reported in the registry record. The endpoint is restricted to escalation, but the record does not provide its count or denominator. It also does not provide the operational definition of a dose-limiting toxicity beyond identifying the outcome and assessment window. This prevents evaluation of the endpoint’s magnitude, precision, and reproducibility from the recorded information.

The study is non-randomized, open-label, and sequential. Dose groups are therefore not like-for-like controls, and observed differences between groups could reflect cohort composition or the process by which doses were studied rather than dose alone. The recorded serious adverse-event counts have varying denominators, and no inferential comparisons are reported. The safety summary also does not establish causal attribution for the deaths listed.

Several design and analysis details are not reported in the registry record: the sample-size justification, detailed dose-escalation rules, analysis populations, missing-data methods, multiplicity procedures, and inferential analysis plan. Full descriptions of the Phase II cohorts are also not available in the recorded details. Although the study description identifies clinical activity and preliminary anti-tumor efficacy as objectives, numerical results for those outcomes are not reported in the registry record.

These limitations concern what can be interpreted from the registry record; they do not establish that the study team did not collect additional information or conduct procedures not described there. They do mean that conclusions should remain limited to the recorded study design and descriptive safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer — NCT04505826.
• Registry record last updated 2026-05-11; status last verified 2026-04.
• Results first posted 2026-05-11.
• 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 identifies NCT04505826 as a completed Phase I and Phase II study of oral OP-1250 in adults with advanced and/or metastatic HR-positive, HER2-negative breast cancer. The study was open-label, non-randomized, sequential, and multicenter. Enrollment is recorded as 153. The recorded study start is 2020-08-13, and primary completion is recorded as 2024-07-30.

The study included Phase I dose escalation and dose expansion and a Phase II monotherapy portion. The primary outcome was the number of participants with dose-limiting toxicities during escalation, assessed up to 28 days from treatment start. A numerical result for that endpoint and any statistical analyses are not reported in the registry record. Descriptive serious adverse-event, other adverse-event, and death counts are listed by dose group. These non-randomized group summaries do not constitute controlled comparisons.