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 Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer (NCT04298918), a randomized phase 1, phase 2 study. The primary outcome is Phase II: ORR.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04298918 |
| Phase | Phase 1, Phase 2 |
| Condition | Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with previously treated HER2-positive locally advanced or metastatic breast cancer. The planned Phase Ib stages included participants with unresectable locally advanced or metastatic disease; the expansion stage could include people previously treated with trastuzumab emtansine or trastuzumab deruxtecan. The randomized Phase II stage was intended for participants who had not previously received trastuzumab emtansine, either alone or with other anti-cancer therapies. The registry record reports that only 1 participant enrolled overall, and it does not report which stage or treatment group included that participant.
Intervention
The investigational combination was venetoclax with trastuzumab emtansine. In Phase Ib, the study was intended to assess safety and tolerability, identify a maximum tolerated dose and recommended Phase II dose, and evaluate preliminary efficacy. The expansion phase was intended to evaluate the combination at the recommended Phase II dose. The Phase II stage was intended to compare the combination with trastuzumab emtansine plus placebo.
Comparator
The planned randomized comparator was trastuzumab emtansine plus placebo. The registry describes the trial as randomized, double-blind, placebo-controlled, and parallel. It does not report actual treatment assignments or how many participants were allocated to each group. Because only 1 participant enrolled and outcome data were withheld, no comparative outcome estimate is available.
Primary question
The listed primary outcome was Phase II objective response rate (ORR), assessed over up to 30 months. The clinical question was whether adding venetoclax to trastuzumab emtansine would be associated with a different ORR than trastuzumab emtansine plus placebo in the planned Phase II population. No ORR result, treatment contrast, or uncertainty estimate is reported in the registry record, so this question remains unanswered by the posted results.
3. Trial Design
The registry describes NCT04298918 as a Phase Ib/II, randomized, double-blind, placebo-controlled, multicenter study with a parallel-group model. Its planned structure combined early-stage dose evaluation with a randomized Phase II comparison. The study was terminated by the sponsor. The registry reports enrollment of 1 participant, which is too limited to support the planned assessment of comparative efficacy or a meaningful characterization of safety across treatment groups.
Phase Ib included a dose-escalation phase and an expansion phase. Dose escalation was intended to assess safety and tolerability, determine the maximum tolerated dose and recommended Phase II dose, and evaluate preliminary efficacy for venetoclax combined with a fixed dose of trastuzumab emtansine. In the expansion phase, participants were to receive venetoclax at the recommended Phase II dose with trastuzumab emtansine. This expansion population could include participants previously treated with trastuzumab emtansine or trastuzumab deruxtecan.
The Phase II stage was designed to evaluate trastuzumab emtansine plus venetoclax at the recommended Phase II dose against trastuzumab emtansine plus placebo. Its planned population had not received prior trastuzumab emtansine, either alone or in combination with other anti-cancer therapies. The registry lists the Phase II primary outcome as ORR, with a timeframe of up to 30 months. It also lists intended assessments of safety, tolerability, pharmacokinetics, duration of response, overall survival, and anti-drug antibodies.
The registry does not report the enrolled participant’s stage, assigned treatment, or follow-up. It also does not report whether the planned dose-escalation, expansion, or randomized procedures were completed. The reasons for termination beyond the statement that the sponsor terminated the study 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.
Before assignment: The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Overall Study
| Stage | Dose Escalation Phase | Dose Expansion Phase | Randomized Phase II Arm 1 | Randomized Phase II Arm 2 |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
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 study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
| Characteristic | Unit | Dose Escalation Phase | Dose Expansion Phase | Randomized Phase II Arm 1 | Randomized Phase II Arm 2 | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | 0 | 0 | |
| Sex: Female, Male: Female | Participants | — | — | — | — | — |
| Sex: Female, Male: Male | Participants | — | — | — | — | — |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | — | — | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Phase II: ORR, measured over Up to 30 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The listed primary endpoint is Phase II objective response rate (ORR), with assessment specified over up to 30 months. In general, ORR describes the proportion of participants who meet a prespecified definition of objective tumor response during a defined assessment period. It is used in oncology trials as a measure of tumor response and can provide a direct summary of how often participants meet that response definition.
Interpreting an ORR requires knowing how response was defined, how it was assessed, which participants were included in the analysis, and how missing or unevaluable assessments were handled. The specific response criteria, assessment schedule, analysis population, and missing-data rules are not reported in the registry record. The endpoint description also gives no response count, response proportion, treatment-group estimate, confidence interval, or test result.
The registry states that the sponsor terminated the study and that only 1 participant enrolled. It further states that no data are reported because of the low enrollment and the need to protect participant privacy and confidentiality. As a result, there is no posted ORR estimate to interpret and no basis for assessing the precision of a treatment comparison. The endpoint identifies the intended efficacy question; it does not establish an observed result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a planned randomized comparison of trastuzumab emtansine plus venetoclax with trastuzumab emtansine plus placebo, but it does not provide comparative efficacy results. The study was terminated by the sponsor after enrollment of 1 participant. The primary outcome description explicitly says that no data are reported because of the low enrollment and participant privacy and confidentiality. Therefore, the posted record does not establish an ORR for either group or a difference between groups.
The registry lists 10 outcome measures and 0 analyses. The primary outcome is labeled Phase II ORR, and the listed timeframe is up to 30 months. There is no posted response count, treatment effect, confidence interval, or p-value. Without an estimate and its uncertainty, there is no statistical basis for determining whether the treatment groups differed, or how compatible the observed data would be with a range of possible effects. No treatment effect should be inferred from the planned design alone.
The adverse-event summary lists zero participants at risk, zero affected, and zero deaths for each of the four named groups: Dose Escalation Phase, Dose Expansion Phase, Randomized Phase II Arm 1, and Randomized Phase II Arm 2. Those entries should not be interpreted as evidence that no adverse events occurred. The registry’s outcome description says that no data are reported because of low enrollment and privacy concerns, and the enrollment count does not establish how participants were distributed among the planned groups. Safety conclusions therefore cannot be drawn from these displayed zeros.
In general, a confidence interval communicates the range of treatment effects reasonably compatible with an estimate under the analysis assumptions. No confidence interval is posted for the primary endpoint, so precision cannot be assessed. Likewise, a p-value would address compatibility with a specified null hypothesis under a statistical model; no such result is reported. The absence of these quantities is not evidence of equivalence, no difference, or lack of an effect. It reflects the absence of reportable outcome data.
The record includes a sample-size-assumption description for planning illustrations: a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the description refers to total events using the Schoenfeld approach; other outcomes are described in participants per arm. These assumptions do not supply an observed treatment effect or a trial result. Since no effect estimate is posted, those planning assumptions cannot provide a data-based assessment of this study’s findings. Any sample-size illustration is planning information, not observed power.
Overall, the registry supports conclusions about the intended design and the reason outcome data were withheld, but not about efficacy or safety. The study’s planned question remains unresolved in the posted results. This distinction matters: a trial can describe a clinically relevant comparison while producing no interpretable estimate when enrollment and reporting do not yield outcome data.
9. Statistical Methods Explained
The study combined a dose-finding component and a randomized comparison. Those components address different statistical questions. Dose escalation is generally used to characterize tolerability across dose levels and inform dose selection; a randomized parallel-group comparison is generally used to estimate differences between assigned treatment strategies. The registry describes these intentions but does not report the operational statistical methods used to carry them out.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the time of assignment, so that a later outcome contrast can be interpreted as a comparison of the assigned strategies, subject to the trial’s conduct and analysis assumptions. The registry labels the Phase II stage randomized and parallel, with trastuzumab emtansine plus placebo as one arm and trastuzumab emtansine plus venetoclax as the other. It does not report the randomization sequence, allocation ratio, stratification factors, or actual assignments. The overall enrollment of 1 participant leaves no reported group-level outcome data for estimating a randomized contrast.
What does masking mean for interpretation?
The registry describes the study as double-blind. In general, masking can reduce the chance that knowledge of treatment assignment affects participant reporting, clinical management, or outcome assessment. The exact parties masked and the procedures used to preserve masking are not reported in the registry record. Masking does not replace randomization, adequate outcome collection, or a prespecified analysis; it is one feature of trial conduct. No outcome results are available to assess how masking affected measurement or interpretation in this study.
How should ORR be analyzed?
In general, ORR is a binary outcome at the participant level: each participant is classified according to whether a prespecified response definition was met. A group response proportion can then be estimated, and a comparison can describe the difference or another contrast between groups. The interpretation depends on the response criteria, assessment timing, analysis population, and handling of participants without evaluable assessments. The registry names ORR as the Phase II primary outcome but does not report these analytic details or any resulting response estimates. With no posted response data, no estimate or comparison can be reconstructed.
What can a confidence interval or p-value tell a reader?
In general, a confidence interval expresses uncertainty around an estimated quantity under the chosen statistical method. A narrow interval indicates more precision than a wide interval, though the interval’s meaning depends on the model and design. A p-value summarizes how inconsistent data are with a specified null hypothesis under a statistical model; it does not measure the probability that a treatment works, nor does it by itself communicate the size or clinical importance of an effect. Neither a confidence interval nor a p-value for ORR is reported in the registry record. With no estimate, neither statistical significance nor precision can be assessed.
What do the planning assumptions mean?
The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says that the effect to detect is a stated fraction of the observed effect. In general, a significance level is a design or analysis threshold used to control the long-run frequency of false-positive findings under a specified framework. Equal allocation describes a planning balance between comparison groups; it is not evidence that the enrolled participant was assigned in a particular way. A normal approximation is a statistical simplification used to estimate distributions or required sample sizes under stated conditions. The record does not report whether these assumptions governed a finalized protocol or a completed analysis.
The same planning description distinguishes time-to-event outcomes, for which it refers to total events using the Schoenfeld approach, from other outcomes expressed as participants per arm. In general, event-based planning for time-to-event analyses focuses on the number of observed events because information about a hazard contrast depends on events, not only on enrollment. These are design concepts, not findings. No event totals or planning outputs are reported in the registry record, and the study has no posted outcome estimates on which to base an observed-effect illustration. A planning sample size is not observed power; power is a design property under assumed effects and conditions, not a retrospective measure of what an uninformative dataset demonstrated.
Why do dose-finding details matter?
In general, dose-escalation methods use accumulating safety information to guide decisions about dose levels, while expansion cohorts can add experience at a selected dose. The appropriate interpretation depends on the dose levels, decision rules, observation windows, toxicity definitions, and analysis approach. The registry states that Phase Ib was intended to determine a maximum tolerated dose and recommended Phase II dose, but the dose-escalation algorithm and decision rules are not reported in the registry record. No dose-level results or safety data are available to assess dose selection.
For this trial, the registry reports 0 analyses and withholds outcome data because enrollment was 1. Consequently, the statistical methods can be described only at the level of the planned design and general concepts. The actual analysis population, estimand, model, treatment-effect measure, multiplicity approach, missing-data strategy, and sensitivity analyses are not reported in the registry record. No recalculated comparison is possible without outcome summaries. The posted information describes an intended investigation, not an analyzable efficacy or safety result.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates several outcomes, treatment contrasts, subgroups, or repeated opportunities to declare a finding. In general, testing many hypotheses without an appropriate strategy can increase the chance of at least one false-positive result. The registry lists 10 outcome measures, including pharmacokinetic concentrations, adverse events, duration of response, overall survival, anti-drug antibodies, and Phase II ORR. The registry record does not report a multiplicity procedure, a hierarchy of confirmatory and exploratory outcomes, or how the primary outcome would be protected against multiplicity.
The analysis population for the primary endpoint is not reported in the registry record. The record also does not report how missing, unevaluable, or incomplete response assessments would have been handled. In general, missing-data rules can affect both the estimated response proportion and its uncertainty, particularly when absence of an assessment is related to participant condition or treatment exposure. No assumptions or sensitivity analyses for missing data are reported.
The record does not report whether the primary analysis was intended to follow randomized assignment, treatment received, or another population definition. It also does not report interim analyses, stopping boundaries, subgroup analyses, or an analysis plan addressing the two study parts. These details should not be inferred from the phase labels or trial design description. Given the stated privacy-based suppression of outcome information, neither multiplicity nor missing-data methods can be evaluated from the posted results.
11. What the Result Does, and Does Not, Mean
The posted record establishes that NCT04298918 was designed to evaluate venetoclax with trastuzumab emtansine, including a randomized Phase II comparison with trastuzumab emtansine plus placebo. It also establishes that the sponsor terminated the study, enrollment was 1 participant, and outcome data were not reported because of privacy and confidentiality concerns. These registry entries describe the status and reporting of the trial; they do not establish a treatment effect.
The record does not show whether venetoclax changed ORR, duration of response, overall survival, safety, tolerability, or pharmacokinetic measures. It also cannot establish that the treatments were equivalent or that there was no difference. No reported estimate with uncertainty is available, and the single enrollment does not provide the group-level evidence needed for the planned comparison. The adverse-event summary’s zero entries are not a substitute for reported safety results, given the registry’s explicit statement that outcome data were withheld.
In general, a null or nonsignificant result is an analyzed result that still has an estimate and a degree of uncertainty. That is different from having no reportable result. Here, the registry does not present an analysis from which efficacy or safety can be inferred. The absence of posted data should therefore be read as an evidence gap, not as a negative finding or confirmation of benefit.
The planned sample-size assumptions do not change this interpretation. A planning illustration addresses what enrollment might be needed under specified assumptions; it does not convert an unavailable outcome into evidence. Because no observed effect is reported, there is no observed effect estimate to interpret and no basis for an effect-based planning comparison. The registry leaves the clinical and statistical question unresolved.
12. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a well-described research question and an answer supported by data. The registry specifies a clinically focused comparison, a randomized double-blind design, a dose-finding component, and a primary efficacy outcome. But design features alone cannot estimate treatment effects. An interpretable comparison depends on participants contributing outcome information and on results being reported with enough detail to assess magnitude and uncertainty.
Enrollment of 1 participant, followed by termination and privacy-based nonreporting, sharply limits what can be learned from the public record. The planned Phase II comparison cannot be evaluated, and the intended Phase Ib dose-selection objectives cannot be assessed. The record consequently illustrates that statistical conclusions depend not only on analysis methods but also on the quantity and availability of outcome data.
It also highlights why zero entries in a safety summary need context. When the registry states that no outcome data are reported, zeros in summary fields cannot be read as evidence of no events. Statistical interpretation requires understanding how records were populated and whether they represent observed outcomes or suppressed information. Here, the registry’s own explanation cautions against treating those entries as clinical findings.
Finally, the record underscores the distinction between planning assumptions and empirical results. A significance threshold, allocation assumption, or sample-size method can describe a design framework, but none answers the treatment question without analyzable outcomes. A careful reader should separate the intended comparison from the evidence actually reported: the former is described; the latter is insufficient for an efficacy or safety conclusion.
13. 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 central limitation is the very small enrollment: the registry reports 1 participant and says that outcome data were not reported to protect privacy and confidentiality. No primary outcome estimate, treatment-group contrast, or uncertainty interval is available. This prevents assessment of ORR and leaves the planned Phase II efficacy question unanswered in the registry record.
The record does not identify the enrolled participant’s study stage, treatment assignment, or follow-up. It therefore cannot establish whether the participant entered dose escalation, expansion, or the randomized Phase II stage. The planned group descriptions do not establish that any particular group was populated. Although the adverse-event summary lists zero entries for at-risk participants, affected participants, and deaths across the four groups, the registry’s nonreporting statement means those entries cannot be interpreted as a complete safety account.
Important design and analysis details are also absent. The registry record does not report the dose-escalation algorithm, response criteria, actual assessment schedule, primary analysis population, missing-data handling, treatment-effect measure, confidence intervals, or multiplicity strategy. It does not report interim analyses or sensitivity analyses. These omissions limit evaluation of how the planned research would have been analyzed, even apart from the lack of outcome data.
Finally, the stated sample-size assumptions are planning concepts rather than trial findings. There is no observed effect estimate to support an effect-based planning illustration, and no inferential analysis is reported. These limitations concern the available registry record and should not be mistaken for evidence that the intended treatments had any particular efficacy or safety profile.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: A Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer — NCT04298918.
- Registry record last updated 2021-11-08; status last verified 2021-10.
- Results first posted 2021-11-08.
- 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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17. Record Summary
NCT04298918 was a Phase Ib/II study of venetoclax with trastuzumab emtansine in previously treated HER2-positive locally advanced or metastatic breast cancer. The planned Phase Ib program included dose escalation and expansion; the randomized, double-blind Phase II stage was designed to compare trastuzumab emtansine plus venetoclax with trastuzumab emtansine plus placebo. The listed primary outcome was Phase II ORR over up to 30 months.
The sponsor terminated the study after enrollment of 1 participant. The registry states that no outcome data are reported because of low enrollment and privacy and confidentiality concerns. It lists 10 outcome measures and 0 analyses. No efficacy estimate, safety conclusion, or randomized treatment comparison can be drawn from the posted results.