This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer (NCT04288089), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04288089 |
| Phase | Phase 1 |
| Condition | Receptors, Estrogen, Genes, Erbb-2, Breast Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eisai Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Women with advanced or metastatic estrogen receptor-positive, HER2-negative breast cancer. The primary endpoint population was the Dose Evaluable Set: participants evaluated for dose-limiting toxicities in the dose escalation part.
Intervention
H3B-6545 given in combination with palbociclib. The registry lists H3B-6545 doses of 150, 300, and 450 mg and palbociclib doses of 75, 100, and 125 mg.
Comparator
There was no separate control group identified. Allocation is listed as NA, and the study is open-label.
Primary question
What is the maximum tolerated dose of the combination, using dose-limiting toxicities in Cycle 1 to identify the highest dose at which no more than 1 of 6 participants experienced a dose-limiting toxicity?
This is a dose-finding question, not a randomized comparison of the combination against another treatment. The primary objective was to evaluate safety and tolerability and determine the maximum tolerated dose and/or recommended Phase 2 dose. The primary endpoint is specifically framed around dose-limiting toxicity during the first 28-day cycle. It therefore addresses whether a dose met the registry’s stated toxicity rule in the dose escalation part; it is not a direct measure of comparative benefit.
The registry lists the study as Phase 1b and describes dose escalation and dose expansion. The posted record does not report a primary endpoint result, an identified maximum tolerated dose, or a recommended Phase 2 dose. Accordingly, the clinical question can be described from the objective and endpoint definition, but its answer cannot be read from the posted results.
3. Trial Design
This is an open-label, multicenter Phase 1b study of H3B-6545 in combination with palbociclib. The model is listed as sequential, while allocation is listed as NA and masking as none. Enrollment is 31. The title and eligibility description identify women with advanced or metastatic estrogen receptor-positive, HER2-negative breast cancer. The registry lists the study status as active, not recruiting.
The study includes dose escalation and dose expansion, according to the arm description. The listed palbociclib doses are 75, 100, and 125 mg, and the listed H3B-6545 doses are 150, 300, and 450 mg. The arm description states that palbociclib is taken orally once daily on Days 1 to 21 followed by 7 days off treatment in 28-day cycles, with H3B-6545 taken orally once daily on Days 1 to 28 in 28-day cycles. The registry’s arm-description text is truncated during its explanation of dose escalation, so further details of the regimen are not reported in the registry record.
The registry identifies four groups in its posted adverse-event data: H3B-6545 300 mg with palbociclib 100 mg; H3B-6545 300 mg with palbociclib 125 mg; H3B-6545 450 mg with palbociclib 125 mg; and H3B-6545 450 mg with palbociclib 100. These safety groups should not be read as randomized arms. There is no separate control group identified, and the record explicitly notes that the arms are not a like-for-like control comparison.
The study start is listed as 2020-04-01, and primary completion is listed as 2022-09-16. The registry record does not report the statistical plan for dose assignment, the sample-size justification, or interim-analysis procedures. The enrollment figure is not itself evidence that every enrolled participant was included in the primary endpoint analysis.
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: This study was planned to be conducted in two parts: Dose Escalation and Dose Expansion. In the Dose Escalation part, a total of 31 participants were enrolled and received the study treatment. However, no participants were enrolled in the Dose Expansion part. In this result summary, data has been reported for dose escalation part only and up to primary completion date (16 September 2022). This study is ongoing and will be updated with final results after study completion.
Overall Study
| Stage | H3B-6545 300 mg + Palbociclib 100 mg | H3B-6545 300 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 100 |
|---|---|---|---|---|
| STARTED | 7 | 8 | 8 | 8 |
| COMPLETED | 5 | 7 | 7 | 4 |
| NOT COMPLETED | 2 | 1 | 1 | 4 |
Reasons for not completing this period:
| Reason | H3B-6545 300 mg + Palbociclib 100 mg | H3B-6545 300 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 100 |
|---|---|---|---|---|
| Ongoing Treatment | 2 | 1 | 1 | 4 |
Analysis population for the primary outcome, as defined in the registry: The Dose Evaluable Set (DES) included all participants who were evaluated for DLTs in dose escalation part.
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: The Full Analysis Set (FAS) included all participants who received at least one dose of study drug.
| Characteristic | Unit | H3B-6545 300 mg + Palbociclib 100 mg | H3B-6545 300 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 100 | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 7 | 8 | 8 | 8 | 31 | |
| Age, Continuous | Years | 62.4 (SD 7.76) | 51.9 (SD 15.61) | 56.0 (SD 4.96) | 59.1 (SD 14.53) | 57.2 (SD 11.80) |
| Sex: Female, Male: Female | Participants | 7 | 8 | 8 | 8 | 31 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 8 | 8 | 6 | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 6 | 8 | 8 | 5 | 27 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 2 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib, measured over Cycle 1 (Cycle length = 28 Days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligram |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of H3B-6545 and palbociclib, measured in milligrams over Cycle 1, whose length is 28 days. The registry defines the maximum tolerated dose as the highest dose at which no more than 1 of 6 participants experienced a dose-limiting toxicity in the dose cohort. Dose-limiting toxicities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, and the listed events had to occur in Cycle 1 with a causal relationship to study drug that could not be ruled out.
The registry’s criteria include specified blood-count, gastrointestinal, electrolyte, kidney, liver, biochemical, and other non-hematologic toxicities, with grade and duration conditions for some events. This definition makes the endpoint a rule for selecting a dose based on early toxicity within dose escalation. It is not a count of all adverse events across the entire study, nor does it measure tumor response or compare treatment benefit with a control.
Such an endpoint is used in early-phase dose-finding research to guide selection of a dose for later study while documenting serious early toxicity. The primary endpoint population is the Dose Evaluable Set, defined as all participants evaluated for dose-limiting toxicities in dose escalation. The posted record does not report the observed dose-limiting toxicity counts by cohort or the resulting maximum tolerated dose.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes the aim and rule for identifying a maximum tolerated dose, but it does not post a result for that primary endpoint. There is no dose-specific DLT summary or reported MTD in the information. As a result, the stated objective cannot be answered from these posted data. The number enrolled, 31, does not substitute for the endpoint analysis: enrollment and inclusion in the Dose Evaluable Set are distinct concepts, and the record does not state how many participants were evaluated for DLTs.
The adverse-event data are descriptive. Four dose groups are shown, with the number at risk and the number affected by serious and other adverse events, as well as deaths. The groups have different reported numbers at risk, and the study is not presented as a randomized comparison. These figures can describe what was recorded in each listed group, but they do not establish that one dose combination caused more or fewer events than another. Differences in raw counts would be especially difficult to interpret without an appropriate comparison design, event definitions, exposure context, and statistical analysis.
The record lists serious-event terms and percentages, including vomiting at 25.0%, atrial fibrillation at 14.3%, asthenia at 14.3%, hypercalcaemia at 14.3%, peripheral embolism at 14.3%, and pancytopenia at 12.5%. Those figures should be read as registry summaries, not as evidence of comparative risk. The denominator and method for each term percentage are not stated in the record excerpt, so they should not be reverse-engineered or treated as directly comparable across terms or groups.
The registry lists 17 outcome measures and zero analyses. That means the record does not include a posted inferential analysis in the material; it does not mean that no analyses were conducted outside the posted record. No estimates, confidence intervals, or p-values for the primary endpoint are reported. Without those, readers cannot assess uncertainty around a dose-finding result or infer whether a particular dose met the MTD rule.
General statistical context: confidence intervals, when reported, describe the range of values compatible with an estimate under the analysis assumptions. In a small, early-phase study, estimates can be imprecise, and descriptive adverse-event counts do not by themselves quantify comparative effects. Here, no confidence interval for the primary endpoint or comparative treatment effect is reported, so the posted information supports a description of study aims and safety summaries, not a quantified efficacy or between-group conclusion.
9. Statistical Methods Explained
The registry characterizes the study as open-label, multicenter, Phase 1b, with a sequential model. Allocation is NA and masking is none. These design labels matter when interpreting the results: there is no randomized control comparison identified, and participants and investigators were not masked according to the record. The purpose described is early evaluation of safety and tolerability to determine an MTD and/or recommended Phase 2 dose.
How the primary endpoint rule works
The MTD definition is based on the dose cohort and the occurrence of DLTs during Cycle 1, a 28-day cycle. The highest dose meeting the rule of no more than 1 of 6 participants with a DLT is designated the MTD under the stated definition. This is a threshold-based decision rule, not a continuous estimate of an average toxicity rate. The registry specifies that a DLT must meet the listed event criteria, occur in Cycle 1, and have a causal relationship with study drug that could not be ruled out. The record identifies CTCAE version 5.0 for grading.
For this type of endpoint, the dose cohort is the unit in which the decision rule is applied. The rule depends on both the number of participants evaluated at a dose and how many meet the DLT definition. Those observed values are not reported. The record also does not state whether additional dose-assignment rules, stopping boundaries, or other modifications were used. They should not be inferred from the endpoint definition alone.
What the safety summaries show
The posted adverse-event section gives counts by named dose group. It separates participants at risk from participants affected by serious adverse events and other adverse events, and also lists deaths. A count of affected participants is a descriptive summary; it is not an estimate adjusted for time receiving treatment or other participant characteristics. The record excerpt does not report such adjustments or a comparative model.
The list of serious-event terms gives percentages for selected terms. Because the record excerpt does not explain the denominator or calculation for those percentages, their intended basis is not reported in the registry record. The percentages can be quoted as posted, but they cannot be used to recover an unreported denominator or compare risks across groups.
Why a randomized comparison is not available
Random allocation helps make groups comparable, on average, for a treatment contrast. This study has allocation listed as NA and is explicitly described as not being a randomized comparison. Its dose groups are part of dose escalation and expansion, not like-for-like controls. Comparisons between their event counts would therefore be descriptive and potentially affected by differences in group composition, dose, treatment exposure, or follow-up. The posted record does not provide an adjusted analysis to address those issues.
What is missing from the inferential record
The record lists zero analyses. It does not report an analysis plan for the primary endpoint, inferential estimates, confidence intervals, or p-values. It also does not report the sample-size justification, planned interim analyses, or a statistical plan for combining dose-escalation and expansion data. These absences limit assessment of how the observed data were intended to answer the objective and how uncertainty was handled.
General statistical context: a confidence interval communicates uncertainty around an estimate, conditional on the assumptions and method used. A p-value addresses compatibility between data and a specified null model; it does not measure clinical importance. Neither can be reconstructed responsibly without the relevant endpoint data and analysis specification. Likewise, a planning sample size is a design calculation, not a measure of the information actually observed. No sample-size justification or sample-size planning result is reported in the registry record for this trial.
Population definitions and missing data
The primary population is the Dose Evaluable Set, defined as participants evaluated for DLTs in dose escalation. This is narrower in purpose than simply counting everyone enrolled. The registry does not state how many enrolled participants met this population definition, how unevaluable participants were handled, or whether any replacement approach was used. It also does not describe missing-data rules for the primary endpoint or adverse-event summaries.
These omissions are important for interpretation. If participants are not evaluable, the number observed in a cohort may differ from the number initially assigned or enrolled. Without the actual analysis population and disposition, readers cannot determine the completeness of DLT observation or reproduce the endpoint classification. The posted record is therefore best read as documenting the endpoint’s definition and the design framework, with descriptive safety summaries, rather than a complete statistical report of dose finding.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 17 outcome measures and zero analyses. It describes a primary endpoint and multiple secondary outcomes, including treatment-emergent adverse events, serious adverse events, and pharmacokinetic measures such as AUC, Cmax, Tmax, C24, and ratios of selected palbociclib parameters across days. The posted record does not describe how inferential testing across these outcomes was planned or whether any adjustment for multiple comparisons was used. A multiplicity strategy is not reported in the registry record.
The record also does not report interim-analysis procedures, a statistical analysis plan, or a sample-size justification. Those details should not be inferred from the Phase 1b designation or the MTD definition. In particular, the available information does not establish whether any analysis was planned to control a family-wise error rate or another measure of false-positive risk. Since no analyses are listed, there are no posted p-values or confidence intervals to interpret in relation to multiple testing.
For the primary endpoint, the Dose Evaluable Set is defined as participants evaluated for DLTs in dose escalation. The record does not give the number in this set or explain how missing, incomplete, or unevaluable Cycle 1 toxicity information was handled. It also does not state whether participants who did not complete Cycle 1 could be included in the DLT assessment, or what procedures applied in that circumstance. Missing-data handling is not reported in the registry record.
The total enrollment is 31, but the record does not provide a participant flow showing how many enrolled participants entered each dose group, completed the relevant observation period, or contributed to each outcome. These gaps prevent readers from judging completeness of the endpoint data or reproducing the analysis population. They also mean that enrollment should not be treated as the denominator for every reported outcome. The safest interpretation is to distinguish the recorded enrollment figure from the endpoint-specific population and to avoid treating unreported analysis choices as known.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| H3B-6545 300 mg + Palbociclib 100 mg | 2 | 7 | 28.6% |
| H3B-6545 300 mg + Palbociclib 125 mg | 2 | 8 | 25.0% |
| H3B-6545 450 mg + Palbociclib 125 mg | 3 | 8 | 37.5% |
| H3B-6545 450 mg + Palbociclib 100 | 3 | 8 | 37.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| H3B-6545 300 mg + Palbociclib 100 mg | 3 of 7 |
| H3B-6545 300 mg + Palbociclib 125 mg | 3 of 8 |
| H3B-6545 450 mg + Palbociclib 125 mg | 4 of 8 |
| H3B-6545 450 mg + Palbociclib 100 | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| H3B-6545 300 mg + Palbociclib 100 mg | 7 of 7 |
| H3B-6545 300 mg + Palbociclib 125 mg | 7 of 8 |
| H3B-6545 450 mg + Palbociclib 125 mg | 8 of 8 |
| H3B-6545 450 mg + Palbociclib 100 | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | H3B-6545 300 mg + Palbociclib 100 mg | H3B-6545 300 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 100 |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 0 of 7 | 0 of 8 | 2 of 8 | 0 of 8 |
| Asthenia | General disorders | 1 of 7 | 0 of 8 | 1 of 8 | 0 of 8 |
| Pancytopenia | Blood and lymphatic system disorders | 0 of 7 | 1 of 8 | 0 of 8 | 0 of 8 |
| Atrial fibrillation | Cardiac disorders | 1 of 7 | 0 of 8 | 0 of 8 | 0 of 8 |
| Myocarditis | Cardiac disorders | 0 of 7 | 0 of 8 | 0 of 8 | 1 of 8 |
| Colitis | Gastrointestinal disorders | 0 of 7 | 1 of 8 | 0 of 8 | 0 of 8 |
| Nausea | Gastrointestinal disorders | 0 of 7 | 0 of 8 | 1 of 8 | 0 of 8 |
| Pancreatitis | Gastrointestinal disorders | 0 of 7 | 0 of 8 | 0 of 8 | 1 of 8 |
| Cholecystitis | Hepatobiliary disorders | 0 of 7 | 0 of 8 | 0 of 8 | 1 of 8 |
| Cholecystitis acute | Hepatobiliary disorders | 0 of 7 | 0 of 8 | 0 of 8 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | H3B-6545 300 mg + Palbociclib 100 mg | H3B-6545 300 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 125 mg | H3B-6545 450 mg + Palbociclib 100 |
|---|---|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | 5 of 7 | 5 of 8 | 4 of 8 | 7 of 8 |
| Anaemia | Blood and lymphatic system disorders | 1 of 7 | 5 of 8 | 4 of 8 | 7 of 8 |
| Fatigue | General disorders | 3 of 7 | 3 of 8 | 6 of 8 | 2 of 8 |
| Neutropenia | Blood and lymphatic system disorders | 4 of 7 | 4 of 8 | 3 of 8 | 2 of 8 |
| Nausea | Gastrointestinal disorders | 2 of 7 | 3 of 8 | 4 of 8 | 4 of 8 |
| Neutrophil count decreased | Investigations | 1 of 7 | 2 of 8 | 4 of 8 | 5 of 8 |
| Vomiting | Gastrointestinal disorders | 2 of 7 | 1 of 8 | 4 of 8 | 2 of 8 |
| White blood cell count decreased | Investigations | 0 of 7 | 2 of 8 | 4 of 8 | 3 of 8 |
| Oedema peripheral | General disorders | 2 of 7 | 3 of 8 | 1 of 8 | 2 of 8 |
| Alanine aminotransferase increased | Investigations | 0 of 7 | 2 of 8 | 3 of 8 | 2 of 8 |
Serious events with the highest arm-level rate: vomiting (25.0%), atrial fibrillation (14.3%), asthenia (14.3%), hypercalcaemia (14.3%), peripheral embolism (14.3%).
The adverse-event summaries list four groups and, for each, the number of participants at risk, the number affected by serious adverse events, the number at risk for other adverse events, the number affected by other adverse events, and deaths. For example, the group titled H3B-6545 300 mg + Palbociclib 100 mg lists 7 at risk for serious events, 2 affected, 7 at risk for other events, 7 affected, and 3 deaths. The other groups are H3B-6545 300 mg + Palbociclib 125 mg; H3B-6545 450 mg + Palbociclib 125 mg; and H3B-6545 450 mg + Palbociclib 100. Refer to the posted tables for the complete group-by-group figures rather than treating these counts as comparative estimates.
Counts of participants with events are not the same as event counts, and the summaries do not, by themselves, establish whether an event was caused by study treatment. The death figures are listed in the safety data, but the excerpt does not report whether deaths were considered treatment-related. It also does not give exposure-adjusted rates or a randomized control group. The listed serious-event terms and percentages are registry summaries; their percentage denominators are not reported in the registry record. Read them as descriptive safety information, not as evidence that one dose combination is safer than another.
12. What the Result Does, and Does Not, Mean
This record establishes that the study was designed to investigate the safety and tolerability of H3B-6545 with palbociclib and to identify an MTD and/or recommended Phase 2 dose. It supplies a rule for the primary endpoint, identifies the dose-evaluable population, and posts adverse-event summaries for four dose groups. Those elements describe the clinical and statistical question the study was set up to address.
However, the posted information does not report the observed DLT results by dose cohort or an MTD determination. It therefore does not show which dose, if any, met the stated rule. Nor does it report a recommended Phase 2 dose. The posted summary also does not provide efficacy results, so it cannot establish a treatment benefit or lack of benefit. The presence of safety counts should not be interpreted as a judgment about whether the combination is appropriate for an individual.
The safety data can be read as counts recorded in the listed groups. Because allocation is NA, the study is not a randomized comparison, and the groups are not identified as like-for-like controls. Their numbers do not support a causal comparison of dose combinations. No inferential analysis, confidence interval, or p-value is listed in the record summary.
General statistical context: early dose-finding studies prioritize learning about tolerability across dose cohorts. Their endpoint definitions can support dose-selection decisions within the study, but the precision of that decision depends on the number of evaluable participants, the observed DLTs, and the analysis procedure. Those outcome details are not reported. The registry record is therefore informative about design and planned endpoint meaning, but insufficient to quantify the primary result or make a comparative claim.
In short, the record documents a dose-finding study and descriptive safety information. It does not provide enough primary-endpoint or analysis detail to determine the selected dose, characterize uncertainty around dose selection, or compare the combination with another treatment.
13. Why This Trial Matters Statistically
This study illustrates a common statistical distinction in early clinical research: a trial can be designed around a clearly defined dose-selection rule without the registry record showing the data needed to apply that rule. Here, the MTD definition specifies the Cycle 1 observation period, the DLT grading framework, and a cohort threshold. Those details make the primary question understandable, but a result still requires the observed DLT experience and the number evaluated in each cohort.
The distinction between enrollment and an endpoint-specific analysis population also matters. The record reports enrollment of 31, while the primary endpoint uses the Dose Evaluable Set, defined by evaluation for DLTs in dose escalation. Without a reported count for that set or cohort-level endpoint results, readers cannot tell how much information contributed to the primary question.
The study also shows why descriptive safety data and randomized treatment comparisons should not be conflated. The registry gives serious and other adverse-event summaries for named dose combinations, but allocation is NA and the record states that the groups are not a like-for-like control comparison. The counts are useful as a description of the posted safety experience, but they do not isolate a causal difference between regimens.
Finally, the absence of a posted analysis plan, sample-size justification, missing-data procedures, and inferential results limits statistical appraisal. These details are needed to understand how dose assignment and incomplete observations were handled and how uncertainty was assessed. The record offers a transparent outline of the objective and endpoint, while leaving the central dose-finding result and its precision unreported.
14. 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 main limitation is that the primary endpoint result is not reported in the registry record. Although the MTD rule and Dose Evaluable Set are defined, the record does not provide DLT counts by cohort, the number evaluated in each cohort, or the resulting MTD. It also does not report an RP2D determination. This prevents readers from assessing whether the primary objective was met or how much uncertainty surrounded dose selection.
The safety summaries do not form a randomized comparison. Allocation is NA, masking is none, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The group counts should therefore be interpreted descriptively. The excerpt does not provide treatment exposure, follow-up duration by group, adjusted analyses, or a stated relationship between deaths and study treatment.
The registry’s arm-description text is truncated, so the full regimen and dose-escalation procedures are not available in the record excerpt. The detailed sample-size rationale, interim analyses, statistical analysis plan, and handling of missing or unevaluable data are also not reported in the registry record. The analysis population size and participant flow are not posted in the posted information. These gaps limit reproducibility and assessment of completeness.
Finally, the adverse-event term percentages are listed without a stated denominator or method in the excerpt. They should be quoted as posted, not recalculated or used to infer group-level rates. The record lists 17 outcomes and zero analyses, with no inferential results for the primary endpoint or comparative treatment effects. Conclusions should therefore remain limited to the design, endpoint definition, and descriptive safety information actually shown.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer — NCT04288089.
- Registry record last updated 2026-08-27; status last verified 2026-08.
- Results first posted 2024-03-22.
- 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.
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18. Record Summary
NCT04288089 is an open-label, multicenter Phase 1b study of H3B-6545 with palbociclib in women with advanced or metastatic ER-positive, HER2-negative breast cancer. It is described as sequential, with allocation listed as NA and masking as none. Enrollment is 31; the registry lists the status as active, not recruiting.
The primary objective is to evaluate safety and tolerability and determine the MTD and/or recommended Phase 2 dose. The primary endpoint defines MTD using DLTs in Cycle 1, with a cohort rule of no more than 1 of 6 participants experiencing a DLT. The primary population is the Dose Evaluable Set in dose escalation.
The record posts adverse-event summaries for four dose groups, but no primary endpoint result or inferential analysis is listed. Sample-size justification, interim-analysis procedures, missing-data handling, and a statistical analysis plan are not reported in the registry record. The posted material describes the study framework and safety summaries, but does not identify the selected dose or quantify uncertainty around the primary result.