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, Tolerability, Pharmacokinetics, And Efficacy Of Venetoclax In Combination With Atezolizumab, Carboplatin, And Etoposide In Participants With Untreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC). (NCT04422210), a non-randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04422210 |
| Phase | Phase 1 |
| Condition | Small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The intended population was people with untreated extensive-stage small cell lung cancer (ES-SCLC). Some maintenance-only cohorts were for participants who had completed 4-6 cycles of first-line carboplatin and etoposide, with or without atezolizumab. The registry does not report further eligibility details in the information available for this analysis.
Intervention
The study evaluated venetoclax with atezolizumab, carboplatin, and etoposide. It planned dose escalation and dose expansion, including induction-plus-maintenance cohorts and maintenance-only cohorts. The registry descriptions list different venetoclax doses and schedules, but do not provide complete descriptions for every cohort.
Comparator
There was no randomized control group. The study was non-randomized and sequential, so its cohorts are not a like-for-like comparison of treatments. Any differences between cohorts would not, by themselves, establish a treatment effect.
Primary question
The registered primary outcome was the number of participants with adverse events (AEs), from baseline until 30 days after the last study-drug dose or until new systemic anti-cancer therapy began, whichever occurred first, up to a maximum of 6.5 weeks. The study also listed response, survival, and pharmacokinetic outcomes. No outcome results are reported in the registry record.
The clinical question therefore combines an early-phase safety and tolerability assessment with planned pharmacokinetic and efficacy assessments. The record describes a study intended to examine venetoclax alongside three other drugs, rather than to isolate the effect of venetoclax in a randomized comparison. Because only 2 participants enrolled and outcome data were withheld to protect confidentiality, the registry cannot answer the safety, efficacy, or pharmacokinetic questions with reported results.
3. Trial Design
This was a Phase 1, non-randomized, unmasked, sequential study with dose-escalation and dose-expansion phases. The registry reports enrollment of 2 participants and status as terminated. The study start date is 2020-09-22 and the primary completion date is 2020-11-06. The sponsor terminated the study; a reason beyond the registry’s statement is not reported in the registry record.
The planned treatments combined venetoclax with atezolizumab, carboplatin, and etoposide. The registry describes maintenance-only cohorts for participants who had completed 4-6 cycles of carboplatin and etoposide, with or without atezolizumab. Other dose-escalation cohorts were intended to receive induction treatment with the combination followed by maintenance if tolerated. The registry also describes a dose-expansion cohort conditional on establishing a recommended Phase 2 dose for venetoclax during induction. That description is a plan, not evidence that expansion occurred.
Sequential dose escalation is designed to explore treatment at successive dose or schedule levels, whereas dose expansion can examine a selected regimen in additional participants. Those are general features of early-phase designs; the exact escalation rules and decision criteria are not reported in the registry record. Because allocation was not randomized and there was no like-for-like control comparison, the cohorts should not be interpreted as parallel treatment groups suitable for estimating comparative effects.
The trial’s small enrollment and termination substantially limit what can be learned from the registered record. It does not report results for safety, response, survival, or drug concentrations. The planned phase structure should therefore be distinguished from the evidence actually reported: the registry documents the design and termination, but not analyzable outcome findings.
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 2 participants were enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Dose Escalation (Arm A1) (Maintenance Only) | Dose Escalation (Arm A2) (Maintenance Only) | Dose Escalation (Arm A3) (Maintenance Only) | Dose Escalation (Arm B1) (Induction + Maintenance) | Dose Escalation (Arm B2) (Induction + Maintenance) | Dose Escalation (Arm B3) (Induction + Maintenance) |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated by the Sponsor. Only 2 participants were 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 2 participants were enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Dose Escalation (Arm A1) (Maintenance Only) | Dose Escalation (Arm A2) (Maintenance Only) | Dose Escalation (Arm A3) (Maintenance Only) | Dose Escalation (Arm B1) (Induction + Maintenance) | Dose Escalation (Arm B2) (Induction + Maintenance) | Dose Escalation (Arm B3) (Induction + Maintenance) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 0 | 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 Number of Participants With Adverse Events (AEs), measured over Baseline up until 30 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 6.5 weeks)..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of participants with adverse events. The registry defines the observation period as baseline until 30 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurred first, with a maximum of 6.5 weeks. This endpoint is a count of participants experiencing an event, not a measure of how often events occurred or how long they lasted.
General statistical context: Counting participants with adverse events is one way to describe safety experience during a specified follow-up period. The observation window matters because participants followed for different lengths of time may have different opportunities to experience and report an event. A count alone also does not convey event severity, duration, attribution to a study drug, or timing unless those details are separately reported.
The registry record does not provide the number of participants with adverse events, event definitions, severity classifications, or event-level results. It states that no data are reported because only 2 participants enrolled and disclosure could threaten participant privacy and confidentiality. Thus, the primary endpoint is defined, but its observed value cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive fact is that the trial enrolled 2 participants and was terminated by the sponsor. The registry explicitly says that outcome data are not reported because the low enrollment could compromise participant privacy and confidentiality. Consequently, the record contains no reported primary endpoint result to estimate or interpret. It does not establish the number of participants who experienced adverse events, and the absence of a reported value is not evidence that no events occurred.
The adverse-event listings show zero participants at risk and zero affected in the listed cohort rows, with zero deaths. Those entries should not be read as observed safety outcomes: the registry’s primary outcome description says data were withheld, and the rows do not supply participant-level event results. The appropriate interpretation is that safety findings are unavailable in the public record, not that the treatment had zero adverse events or deaths.
The registry lists secondary outcomes including duration of response, progression-free survival, overall survival, survival rates at specified time points, and plasma or serum concentrations of study drugs. Results for these outcomes are not reported in the registry record. No effect estimate, confidence interval, test statistic, or p-value is available to establish the size or precision of any efficacy or pharmacokinetic finding.
There is also no randomized comparator. Even if cohort-level results were available, this non-randomized, sequential design would not support a straightforward causal comparison between dose groups. Participants in different cohorts may differ in treatment phase, prior therapy, dose, schedule, and other characteristics. The record does not provide enough outcome information to assess any such differences in this study.
General statistical context: An estimate describes the observed pattern in a sample, while its precision reflects how much uncertainty remains about the underlying population value. Very limited enrollment generally leaves substantial uncertainty, but no interval can be evaluated because outcome values were not reported. The registry’s privacy-based suppression also means the published record is intentionally not a complete numerical account of participant outcomes.
Accordingly, the record supports conclusions about the study’s design, enrollment, termination, and reporting status. It does not support a numerical conclusion about safety, efficacy, pharmacokinetics, or differences among dose cohorts. No recalculated treatment effect is available, and there is no sponsor-reported analysis to compare against a recalculation.
9. Statistical Methods Explained
The registry describes a Phase 1 study organized around dose escalation and a possible dose-expansion phase. It does not report a statistical analysis plan or the decision rules used to move between doses. The design labels describe the intended structure, but they do not reveal how safety observations were evaluated, how a recommended Phase 2 dose would be selected, or what evidence would trigger expansion.
What does non-randomized, sequential allocation imply?
The study was non-randomized and sequential. In general, randomization aims to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. Without randomization, participants entering different cohorts may differ for reasons other than the treatment dose or schedule. Sequential dose escalation also means cohorts may enter at different stages of the study process. Therefore, comparisons across cohorts would be descriptive rather than a randomized estimate of treatment effect.
The registry does not identify a control arm. The intended cohorts differed in whether they received maintenance treatment alone or induction followed by maintenance, and in planned venetoclax dose or schedule. Those cohort differences make direct between-cohort contrasts difficult to interpret even if outcomes had been reported. A non-randomized design can still describe observed tolerability or drug concentrations, but causal claims require assumptions and evidence beyond a simple comparison of group results.
Why are no estimates or confidence intervals available?
The primary endpoint is defined as the number of participants with adverse events during the specified observation period. However, the registry states that outcome data are withheld because only 2 participants were enrolled and publication could threaten privacy and confidentiality. A count, proportion, interval, or other summary cannot be recovered from that statement. The zero entries in the cohort listings do not replace the withheld outcome data and should not be interpreted as proof of no events.
General statistical context: A confidence interval is a range of values compatible with the data and a stated statistical procedure. It communicates uncertainty around an estimate; it does not repair limitations in the design or create information where outcome data are unavailable. Since no endpoint estimate is reported, no confidence interval or precision assessment can be made from this record.
What does the record say about hypothesis testing?
No analyses are reported. The registry record does not report p-values, hypothesis tests, or inferential comparisons. It also does not report a statistical analysis plan specifying models, estimands, covariate adjustment, or methods for handling repeated measurements. Such details should not be inferred from the fact that the study had dose-escalation and dose-expansion phases.
General statistical context: A p-value, when used, measures how incompatible data are with a specified null model under the assumptions of a test. It does not measure the probability that a treatment works, and it does not express the size or clinical importance of an effect. In this study, there are no reported tests to interpret.
How should the sample-size planning illustrations be understood?
There is no observed effect reported from which to make a data-based planning illustration for a treatment comparison. Any planning illustration based on an observed effect is distinct from the trial’s own design and is not observed power. In general, planning calculations describe assumptions about a future study, such as the effect to detect and the chosen error rate; they do not show that a study with a given enrollment had a particular probability of finding an effect. The registry does not report the trial’s own sample-size justification.
General statistical context: A sample-size calculation depends on the design, outcome type, target effect, variability, allocation, and statistical method. If assumptions do not match a study’s design or the outcome data are unavailable, the calculation should not be treated as a summary of what the study found. Here, the non-randomized design and absent endpoint results prevent an observed treatment-effect calculation.
What can the listed outcome measures establish?
The registry lists safety, response, survival, and pharmacokinetic outcomes, but the outcome results are not reported. A named endpoint indicates what the study planned to assess; it is not itself an observation. For time-to-event outcomes, interpretation would ordinarily depend on follow-up and event information, while concentration outcomes require reported measurements at specified time points. Neither is available in the registry record.
In short, the available statistical information is chiefly structural: study phase, allocation, masking, sequential model, enrollment, endpoint definition, and reporting status. No estimate or analysis can be independently checked, and the detailed analysis methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including adverse events, duration of response, progression-free survival, overall survival, survival rates at specified times, and drug concentrations. When a study evaluates multiple outcomes or makes multiple statistical tests, the chance of at least one apparently unusual result can increase. General statistical context: Multiplicity procedures can address that issue by defining a hierarchy, adjusting error rates, or distinguishing confirmatory from exploratory outcomes.
The registry record does not report a multiplicity strategy, testing hierarchy, or confirmatory-versus-exploratory designation. It also reports no analyses or p-values, so there are no multiplicity-adjusted or unadjusted findings to interpret. The primary outcome is identified, but that designation alone does not establish how secondary outcomes were to be analyzed.
Outcome data are not reported because only 2 participants enrolled and the sponsor cited privacy and confidentiality. This is a reporting limitation, not a description of how missing participant observations were handled during analysis. The registry record does not report whether any measurements were missing, how missing measurements would be managed, or whether participants were excluded from particular outcome analyses.
Analysis populations are not reported in the registry record. In particular, the record does not specify an intention-to-treat, safety, pharmacokinetic, or evaluable population definition for the posted outcomes. The number of participants enrolled is known, but that does not establish how many contributed to any specific analysis.
General statistical context: Missing-data methods depend on why values are missing, the timing of missingness, the endpoint, and assumptions about unobserved outcomes. Privacy-based suppression of results is different from missing observations within an analysis dataset. With no reported endpoint values or analysis populations, neither missing-data assumptions nor the impact of missingness can be evaluated.
11. What the Result Does, and Does Not, Mean
The registry record documents a study intended to evaluate venetoclax in combination with atezolizumab, carboplatin, and etoposide, including planned dose escalation, possible dose expansion, and safety, pharmacokinetic, and efficacy outcomes. It also documents that the study was Phase 1, non-randomized, unmasked, sequential, and terminated, with enrollment of 2 participants. These are details about the conduct and reporting status of the trial.
The posted record does not report numerical results for the primary adverse-event outcome or the listed secondary outcomes. It therefore cannot show how many participants experienced adverse events, what responses occurred, how long participants remained progression-free or alive, or what drug concentrations were observed. The absence of reported outcomes must not be confused with an observed value of zero or with evidence of no effect.
The design also limits comparative interpretation. There was no randomized control group, and the cohorts were planned around different doses, schedules, and treatment phases. Even with outcome data, a simple difference among these cohorts would not automatically identify a causal effect of dose or regimen. The registry does not report an analysis to address such differences.
General statistical context: Statistical evidence is strongest when the design, outcomes, analysis methods, and uncertainty estimates are all available and aligned with the research question. A study’s intended aims and its observed results are separate: planned assessments do not establish findings, and a registered endpoint without a result cannot answer the endpoint question.
The appropriate conclusion is limited: the record describes the study plan and its early termination but provides no public outcome estimates to assess. It neither demonstrates benefit nor establishes harm, and it cannot determine the safety or efficacy of the combination. This interpretation concerns the content and limits of the registry record, not a clinical recommendation.
12. Why This Trial Matters Statistically
This study illustrates an important distinction in clinical-trial reporting: a detailed design can be registered even when no outcome estimates are made public. The record identifies the intended population, combination regimen, dose-escalation structure, primary safety endpoint, and planned secondary outcomes. But only 2 participants enrolled, the study was terminated, and the registry states that results were withheld to protect privacy and confidentiality. The design therefore cannot be treated as equivalent to evidence about the outcomes.
For biostatisticians and clinical researchers, the case also emphasizes the difference between a cohort description and a comparative estimate. A non-randomized, sequential dose-escalation study has a different inferential purpose from a randomized comparison. Dose cohorts can inform early-stage decisions when sufficient information is collected and reported, but cohort labels do not create a control group or remove confounding.
General statistical context: Small studies can be useful for questions such as feasibility, dose selection, or initial safety characterization, but estimates from small samples are generally imprecise. When data are suppressed and no estimates are available, even descriptive conclusions are limited. Transparency about what was planned, what was conducted, and what was reported is essential to prevent readers from interpreting missing results as favorable or unfavorable findings.
This record is therefore statistically instructive less for an estimated treatment effect than for the boundaries of interpretation. It shows why study design, enrollment, analysis, and reporting status must be considered together. The existence of planned efficacy and pharmacokinetic outcomes does not substitute for measurements, and the absence of posted findings should remain an explicit uncertainty rather than being recast as a result.
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 most consequential limitation is that outcome results are not reported. The registry explicitly attributes this to enrollment of only 2 participants and a need to protect privacy and confidentiality. As a result, the primary endpoint and the listed secondary outcomes cannot be quantified or independently evaluated. The reason for termination beyond the sponsor’s decision is not reported in the registry record.
The design was non-randomized and sequential, with no like-for-like control comparison. The planned cohorts varied in treatment phase, venetoclax dose, or schedule. This limits the interpretation of any potential contrasts between cohorts, and no cohort-level results are available to assess in any case. The record does not report detailed dose-escalation rules or the criteria for selecting a recommended Phase 2 dose.
Important statistical details are also absent. The analysis plan, sample-size justification, analysis populations, missing-data methods, multiplicity approach, and inferential procedures are not reported in the registry record. The outcome descriptions identify the planned measures but do not provide estimates, uncertainty intervals, or participant-level event summaries.
The listed adverse-event cohort entries contain zeros, but they do not provide usable event results in light of the registry’s explicit statement that outcome data were withheld. They should not be interpreted as evidence that no adverse events or deaths occurred. Overall, the record supports a description of the trial’s structure and reporting status, but not an assessment of its clinical outcomes or statistical precision.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: A Study Evaluating The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Venetoclax In Combination With Atezolizumab, Carboplatin, And Etoposide In Participants With Untreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC). — NCT04422210.
- 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
The registry record describes a Phase 1, non-randomized, unmasked, sequential study of venetoclax with atezolizumab, carboplatin, and etoposide for untreated ES-SCLC. It planned dose escalation and dose expansion, with safety as the primary outcome and response, survival, and pharmacokinetic measures among the secondary outcomes. The study was terminated by the sponsor after enrollment of 2 participants. The recorded start date is 2020-09-22 and the primary completion date is 2020-11-06.
No outcome data are reported because the registry states that the low enrollment could compromise participant privacy and confidentiality. The record therefore does not provide numerical safety, efficacy, survival, or pharmacokinetic findings. Its design and status can be described, but no treatment effect or outcome precision can be assessed.