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 Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy (NCT03655444), a non-randomized phase 1, phase 2 study. The primary outcome is Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03655444 |
| Phase | Phase 1, Phase 2 |
| Condition | Head and Neck Squamous Cell Carcinoma |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
People with recurrent or metastatic head and neck squamous cell carcinoma that progressed or recurred within six months after platinum-based chemotherapy. The registry record says only Phase I participants were evaluable for the primary outcome.
Intervention
Abemaciclib combined with nivolumab. The Phase I description specifies abemaciclib 150 mg orally twice per day and nivolumab 480 mg intravenously on Day 1 of each four-week cycle. The Phase II description includes an abemaciclib monotherapy lead-in before combination treatment.
Comparator
No concurrent control arm is described. The study is non-randomized and sequential. The Phase II rationale refers to a historical one-year survival comparison, but the registry record does not report a controlled comparison within the trial.
Primary question
In Phase I, what recommended Phase II dose of abemaciclib can be combined with a fixed dose of nivolumab under the stated dose-limiting toxicity rule? The registry record does not report the resulting dose.
3. Trial Design
This is a Phase I and Phase II, non-randomized, unmasked, sequential study of abemaciclib with nivolumab. The registry record describes Phase I as a dose de-escalation study to identify a recommended Phase II dose of abemaciclib alongside a fixed dose of nivolumab. In Phase II, the stated aim was to evaluate one-year survival for the combination in people whose disease progressed or recurred within six months after platinum-based chemotherapy.
The Phase I treatment description specifies abemaciclib 150 mg twice per day on Days 1 through 28 of each four-week cycle, with nivolumab 480 mg intravenously on Day 1. The Phase II description includes an abemaciclib monotherapy lead-in at the recommended dose before combination treatment. The registry also lists tumor biopsy, peripheral blood, and EORTC QLQ-30 among the interventions or procedures.
The listed enrollment is 6. The study began on 2019-05-29, and primary completion is recorded as 2020-08-24. Its status is terminated. The reason for termination is not reported in the registry record. The record lists seven outcome measures and zero analyses, but does not provide a Phase II survival result, tumor-response result, or the recommended dose selected in Phase I.
Because allocation was non-randomized and no concurrent control is described, this design does not support a like-for-like treatment comparison. The historical survival figure in the study rationale is background for the Phase II aim, not a randomized control group within the trial.
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.
Overall Study
| Stage | Phase I: Abemaciclib + Nivolumab | Phase II: Abemaciclib + Nivolumab |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Only phase I participants were evaluable for this outcome measure.
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.
| Characteristic | Unit | Phase I: Abemaciclib + Nivolumab | Phase II: Abemaciclib + Nivolumab | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 3 | 6 | |
| Age, Continuous | years | 62 (46 to 76) | 62 (60 to 63) | 62 (46 to 76) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): White | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | 3 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab, measured over Completion of enrollment to Phase I portion of study (estimated to be 3 months).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg twice per day |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the Phase I determination of the recommended Phase II dose of abemaciclib combined with a fixed dose of nivolumab. It is expressed as a number in mg twice per day. The registry defines the recommended dose as the highest dose level at which fewer than 2 people in a cohort of three experience a dose-limiting toxicity during the first cycle. Only Phase I participants were evaluable for this outcome.
In general, an early-phase dose-finding endpoint helps guide the dose used in later study by applying a prespecified toxicity rule to treatment experience. The rule is not a measure of tumor response or survival; it focuses on dose-limiting toxicity within the specified observation period. A dose selected by such a rule would be an outcome of the dose-finding process, not proof of efficacy.
The registry record does not report the dose levels evaluated, the number of dose-limiting toxicities, or the resulting recommended Phase II dose. It therefore describes how the primary outcome was defined, but does not permit interpretation of the dose actually selected or the evidence supporting that selection.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a study with two planned stages and distinct aims. Phase I was intended to identify a dose of abemaciclib for combination with nivolumab using a first-cycle dose-limiting toxicity rule. Phase II was intended to assess one-year survival and other outcomes. The available record does not report the Phase I dose-finding result or Phase II efficacy findings, so neither aim can be judged from the posted results.
The trial is listed as non-randomized, unmasked, and sequential. There is no concurrent control group described. The historical one-year survival figures in the rationale—36% with nivolumab and a target of 60% with the combination—describe the Phase II objective; they are not observed results for the participants in this study. No survival estimate, confidence interval, or comparison test is reported in the registry record.
The listed enrollment is 6. This number alone does not establish how many participants contributed to each phase or outcome. The record explicitly says only Phase I participants were evaluable for the primary dose outcome, but does not give an outcome-specific analysis population or the number contributing to each secondary measure. The reason for termination is also not reported in the registry record.
Safety entries list 3 of 6 at risk with serious adverse events, 6 of 6 at risk with other adverse events, and 3 deaths. These are descriptive counts in the combined Phase I and Phase II group. They do not establish that an event was caused by treatment, and the record does not provide timing, exposure-adjusted rates, or an attribution analysis. The listed serious adverse event terms include lung infection at 33.3%, dysphagia at 16.7%, increased aspartate aminotransferase at 16.7%, acute kidney injury at 16.7%, and non-cardiac chest pain at 16.7%. These percentages describe listed terms; the registry record does not explain whether participants could contribute to more than one term.
In general, small, uncontrolled studies can describe observed events and generate questions, but they do not separate treatment effects from disease course, other care, or chance. No precision estimate accompanies the safety counts in the record. Nor does the absence of reported efficacy results mean that an outcome was absent; it means the registry record does not report it. Any interpretation should therefore remain limited to the design, outcome definitions, and posted descriptive safety information.
9. Statistical Methods Explained
What does the design tell us?
The registry describes a sequential study, with Phase I dose finding followed by a planned Phase II evaluation. In general, a sequential design can use an earlier stage to inform a later stage, but the details of how progression between stages was governed are not reported in the registry record. The study is non-randomized and unmasked. Consequently, treatment assignment was not described as random, and no concurrent control arm is reported. A comparison with historical survival is not equivalent to a randomized comparison because the historical group is not enrolled and followed alongside the study group under the same conditions.
How does the primary dose rule work?
The primary outcome is a dose selection based on dose-limiting toxicity during the first cycle. The registry defines the recommended Phase II dose as the highest dose level at which fewer than 2 people in a cohort of three experience a dose-limiting toxicity in that period. In general, a rule of this kind translates early safety observations into a dose decision. It does not estimate a comparative treatment effect, and the result depends on the dose levels assessed and the observed toxicities at each level. The dose levels actually evaluated and the resulting selection are not reported in the registry record.
What can be inferred from the listed outcomes?
The registry lists the primary Phase I dose outcome, as well as Phase II tumor response and duration of response, progression-free survival, adverse events, and Phase II lead-in changes in peripheral blood lymphocyte subsets. These outcomes address different questions and require outcome-specific definitions and analysis populations. The record does not give Phase II outcome estimates or analyses. It lists zero analyses, so no statistical test, model, confidence interval, or adjusted estimate is reported there.
In general, a confidence interval conveys uncertainty around an estimated quantity; its width depends on the amount and variability of relevant data and the analysis method. Without an outcome estimate and interval, the precision of a treatment effect cannot be assessed. For time-to-event outcomes, censoring and the definition of the event and follow-up period matter. The registry record does not provide a Phase II survival estimate or the associated analysis details.
How should the planning assumptions be read?
The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a chosen fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; for other illustrations, it is participants per arm. These are planning calculations, not observed power and not the trial's own design. Equal allocation between two arms is an illustrative assumption, not a description of this non-randomized study. The record does not report a trial-specific sample-size justification or the numerical planning estimates.
In general, power calculations are conditional on assumptions about the effect to detect, variability, allocation, and analysis. A planning illustration does not show that a study achieved a particular power after data collection. It also cannot replace a report of observed estimates and uncertainty. No power calculation should be interpreted as evidence that the trial did or did not demonstrate a clinical effect.
Why does over-dispersion matter in general?
For count outcomes, a model may assume that variability follows a particular relationship to the mean. Over-dispersion means the observed variability is greater than that assumption allows. If not accommodated, uncertainty can be understated and statistical tests can appear more decisive than warranted. This is a general consideration for count-data methods; the registry record does not report a count model or indicate that over-dispersion was assessed in this trial.
Overall, the record provides a design description, a dose-finding rule, outcome names, and descriptive safety figures. It does not provide enough analysis detail to reconstruct a treatment-effect analysis, evaluate model assumptions, or assess the precision of efficacy outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several outcomes across the Phase I and Phase II stages, including dose selection, tumor response, duration of response, progression-free survival, adverse events, and immune-cell changes. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if each is tested separately. In general, a multiplicity plan may define a primary comparison, adjust thresholds, or describe which analyses are exploratory. Such a plan is not reported in the registry record.
The primary outcome is restricted to Phase I participants. The record does not describe the analysis population for each other outcome, how participants with incomplete follow-up were handled, or whether missing measurements were imputed or excluded. The extent and reasons for missing data are not reported in the registry record. Those details matter because the amount and pattern of missingness can affect which participants contribute to an estimate and how representative it is.
The record lists zero analyses. It therefore does not report the statistical tests, models, confidence intervals, covariate adjustments, or multiplicity procedures used for any efficacy outcome. An analysis plan, interim-analysis plan, and sample-size justification are not reported in the registry record. No assumptions about these procedures should be inferred from the study's phase labels or outcome list.
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 |
|---|---|---|---|
| Phase I and Phase II: Abemaciclib + Nivolumab | 3 | 6 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase I and Phase II: Abemaciclib + Nivolumab | 3 of 6 |
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 |
|---|---|
| Phase I and Phase II: Abemaciclib + Nivolumab | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I and Phase II: Abemaciclib + Nivolumab |
|---|---|---|
| Lung infection | Infections and infestations | 2 of 6 |
| Dysphagia | Gastrointestinal disorders | 1 of 6 |
| Aspartate aminotransferase increased | Investigations | 1 of 6 |
| Acute kidney injury | Renal and urinary disorders | 1 of 6 |
| Non cardiac chest pain | General disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I and Phase II: Abemaciclib + Nivolumab |
|---|---|---|
| Creatinine increased | Investigations | 6 of 6 |
| Lymphocyte count decreased | Investigations | 6 of 6 |
| Anemia | Blood and lymphatic system disorders | 5 of 6 |
| Fatigue | General disorders | 5 of 6 |
| Nausea | Gastrointestinal disorders | 4 of 6 |
| Weight loss | Investigations | 4 of 6 |
| Hyperglycemia | Metabolism and nutrition disorders | 4 of 6 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 6 |
| Diarrhea | Gastrointestinal disorders | 3 of 6 |
| Vomiting | Gastrointestinal disorders | 3 of 6 |
Serious events with the highest arm-level rate: lung infection (33.3%), dysphagia (16.7%), aspartate aminotransferase increased (16.7%), acute kidney injury (16.7%), non cardiac chest pain (16.7%).
The safety group is labeled “Phase I and Phase II: Abemaciclib + Nivolumab.” The registry lists 3 of 6 at risk with serious adverse events, 6 of 6 at risk with other adverse events, and 3 deaths. These are counts in the recorded group, not a comparison against an untreated or randomized control group. The record does not state that the deaths were caused by treatment, nor does it report the timing or circumstances of each death.
The listed serious adverse event terms are lung infection at 33.3%, dysphagia at 16.7%, increased aspartate aminotransferase at 16.7%, acute kidney injury at 16.7%, and non-cardiac chest pain at 16.7%. The registry record does not clarify whether these terms overlap within participants, how event severity or relatedness was assessed, or whether the terms represent all serious events observed.
In general, adverse-event counts describe what was recorded during a study; they do not by themselves establish causation. Without a concurrent comparator, exposure duration, event timing, and attribution details, the figures cannot isolate the contribution of the treatment combination.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a non-randomized, sequential Phase I and Phase II study of abemaciclib with nivolumab was registered for recurrent or metastatic head and neck squamous cell carcinoma. It specifies a Phase I dose-finding rule and describes Phase II aims that include one-year survival and tumor-related outcomes. It also records safety counts and deaths for the combined treatment group.
It does not establish the recommended Phase II dose, because that result is not reported. It does not establish whether the Phase II survival aim was met: no survival estimate or Phase II efficacy analysis is reported. The historical comparison in the study rationale is a target-setting statement, not a result observed in a concurrent comparison. The non-randomized design also means that the record does not provide a like-for-like control comparison.
The safety entries should be read as descriptive observations, not as proof that treatment caused an event or death. The record does not provide event attribution, timing, or comparative rates. The listed enrollment is 6, but the registry does not specify outcome-specific analysis populations beyond saying that only Phase I participants were evaluable for the primary dose outcome.
In general, absence of a reported estimate is not evidence of no effect, just as a recorded event is not proof of treatment causation. Conclusions about benefit, harm, or the precision of an effect require outcome results and analysis details that are not reported in the registry record. The listed status is terminated; the reason for termination is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for separating an early dose-finding question from a later efficacy question. The Phase I endpoint applies a defined first-cycle toxicity rule to select a dose, while the Phase II rationale concerns one-year survival. Those are different estimands: one concerns dose selection under a safety criterion, and the other concerns a time-to-event outcome.
The design also illustrates why a historical benchmark must be distinguished from a concurrent control group. The Phase II rationale states a historical one-year survival of 36% with nivolumab and a target of 60% with the combination. These values describe the study's rationale; they are not randomized trial results. Differences between a historical reference and a study cohort can reflect factors other than treatment, so the comparison cannot by itself provide the same causal interpretation as randomized allocation.
The registry record lists 6 participants and is marked terminated, but does not report the primary dose result or Phase II efficacy analyses. This makes transparent reporting of analysis populations, endpoint results, follow-up, and reasons for stopping especially important to interpretation. The record also lists serious adverse events and deaths without enough detail to attribute them to treatment or compare risk against another group.
In general, this example underscores that a trial's intended question, its design, and its reported results are separate things. A clear protocol objective does not substitute for outcome estimates, and descriptive observations do not answer a comparative treatment question.
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.
Several trial-specific limitations constrain interpretation. The study is non-randomized and unmasked, and no concurrent comparator is described. The historical survival comparison in the Phase II rationale cannot serve as a randomized control within this study. The record does not report adjustment methods or details that could address differences between a study cohort and a historical reference.
The listed enrollment is 6, and the status is terminated. The reason for termination is not reported in the registry record. The record does not report the recommended Phase II dose, dose-limiting toxicity observations, or Phase II efficacy results. It also does not provide outcome-specific analysis populations beyond the statement that only Phase I participants were evaluable for the primary outcome.
Safety interpretation is limited by the absence of event timing, duration of exposure, attribution, and a comparator. The record does not clarify whether the serious adverse event terms overlap, or provide additional details on the three deaths. Missing-data handling, follow-up completeness, and the statistical analysis plan are not reported in the registry record.
These limitations do not show that an outcome was favorable or unfavorable. They define what can be concluded from the registry record: the study's planned questions and design are described, but the primary dose-finding result and efficacy analyses are not available there.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy — NCT03655444.
- Registry record last updated 2020-12-03; status last verified 2020-11.
- Results first posted 2020-12-03.
- 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
NCT03655444 is a Phase I and Phase II, non-randomized, unmasked, sequential study sponsored by Washington University School of Medicine. It evaluated abemaciclib with nivolumab in recurrent or metastatic head and neck squamous cell carcinoma, with eligibility focused on disease progression or recurrence within six months after platinum-based chemotherapy. Listed enrollment is 6, and the study status is terminated.
The primary outcome is Phase I selection of a recommended Phase II abemaciclib dose based on dose-limiting toxicity during the first cycle. The registry record does not report the selected dose or Phase II efficacy results. It lists adverse-event counts and deaths for the combined treatment group, but not their treatment attribution. The reason for termination, missing-data handling, analysis populations for secondary outcomes, and statistical analysis plan are not reported in the registry record.