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 Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer (NCT02846792), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose of Plinabulin and Nivolumab (Phase I).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02846792 |
| Phase | Phase 1, Phase 2 |
| Condition | ALK Gene Translocation, EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Washington |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with advanced non-small cell lung cancer, including stage IIIB-IV, recurrent, or metastatic disease. The official title describes patients whose disease had progressed through first-line platinum doublet chemotherapy. The registry’s listed conditions also include tumors with ALK gene translocation, EGFR activating mutation, and ROS1 gene translocation. The primary-endpoint population note says the study terminated prematurely and notes that immunotherapy was approved for NSCLC in the first-line setting. Further eligibility details are not reported in the registry record.
Intervention
The treatment combined plinabulin, a drug, with nivolumab, a biological intervention. The arm description says participants received both by intravenous infusion on days 1 and 15, with courses repeating every 28 days in the absence of disease progression or unacceptable toxicity. The trial description frames the investigation as a study of side effects and dose, as well as how the combination performs in this patient population. The registry does not report a treatment-effect estimate.
Comparator
There was no separate comparator group. The registry describes a single-group model, with allocation recorded as not applicable and masking recorded as none. Consequently, the record does not offer a randomized, like-for-like comparison against nivolumab alone, another treatment, or a control condition. Any outcomes in the treated group cannot by themselves isolate the contribution of either drug or establish how the combination compares with another approach.
Primary question
The primary phase I question was the maximum tolerated dose of plinabulin and nivolumab, assessed over up to 28 days. The endpoint definition sets a dose-limiting toxicity rule: no more than 1 of 6 patients experiencing such toxicity, graded using National Cancer Institute Common Toxicity Criteria version 4.0. The registry does not report a maximum tolerated dose or a result for this endpoint. The trial was terminated, and the enrollment recorded was 5, so the posted record does not establish whether the stated endpoint criterion was met.
3. Trial Design
This was a phase I/II clinical trial sponsored by the University of Washington. It used a single-group model with no masking; allocation is recorded as not applicable. The one treatment arm combined plinabulin and nivolumab. The registry describes an intravenous schedule on days 1 and 15, with courses repeating every 28 days while disease had not progressed and toxicity remained acceptable. The record does not describe a parallel control arm or a randomized comparison.
The trial title and summary describe patients with stage IIIB-IV, recurrent, or metastatic non-small cell lung cancer. The official title further specifies advanced disease that had progressed through first-line platinum doublet chemotherapy. The listed conditions include recurrent disease, stage IIIB and stage IV disease, and tumors with ALK gene translocation, EGFR activating mutation, or ROS1 gene translocation. The registry does not report the full eligibility criteria, so these labels should not be taken as a complete description of who could participate.
The primary phase I endpoint was maximum tolerated dose, defined by the dose-limiting-toxicity rule over up to 28 days. The registry also lists disease control rate, duration of response, overall survival, toxicity rates, and progression free survival as secondary outcomes. It records seven outcome measures, but the posted record does not include analysis results for them. It records no analyses.
The study started on 2017-06-14, and the primary completion date is 2018-07-12. Its status is terminated. Enrollment is recorded as 5. The endpoint population note explicitly says the study stopped prematurely and mentions immunotherapy approval for NSCLC in the first-line setting. The registry does not describe the termination decision in further detail, nor does it report the planned statistical design, dose-escalation procedures, or a sample-size justification.
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: Five patients were consented and treated.
Overall Study
| Stage | Treatment (Plinabulin, Nivolumab) |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Study terminated (stopped prematurely). Immunotherapy approved for NSCLC in the first line setting.
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: Baseline participant measures are based on total eligible, consented and treated patients.
| Characteristic | Unit | Treatment (Plinabulin, Nivolumab) |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 4 |
| Age, Continuous | years | 70 (59 to 73) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose of Plinabulin and Nivolumab (Phase I), measured over Up to 28 days.
| 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 is the maximum tolerated dose of plinabulin and nivolumab in the phase I part of the trial. It is a dose-finding endpoint rather than a direct measure of tumor response or survival. The registry defines the criterion as no more than 1 of 6 patients experiencing a dose-limiting toxicity during a timeframe of up to 28 days. Toxicities were to be graded according to National Cancer Institute Common Toxicity Criteria version 4.0.
In general, a maximum-tolerated-dose endpoint is used to identify a dose level meeting a protocol-defined safety boundary. The precise interpretation depends on how doses were selected and escalated, how dose-limiting toxicities were defined, and how participants were evaluated. Those design details are not reported in the registry record, so the criterion alone does not describe the full dose-finding method.
The record does not report an estimated maximum tolerated dose or say whether the toxicity criterion was met. Its population note says the study terminated prematurely. Enrollment is recorded as 5, while the endpoint definition refers to a criterion involving 6 patients. The record does not explain how this difference affected endpoint assessment. Therefore, the endpoint definition is available, but a primary-endpoint result cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study’s design and limited posted safety information, but it does not support an estimate of treatment efficacy. This was a single-group trial of nivolumab plus plinabulin, with no separate comparator. Its primary phase I objective concerned the maximum tolerated dose, and the registry does not report that endpoint’s result. It also records zero analyses. Although disease control rate, duration of response, overall survival, toxicity rates, and progression free survival are listed as secondary outcomes, results for those outcomes are not reported in the registry record.
The record states that enrollment was 5 and that the study terminated. Its primary-endpoint population note says the study stopped prematurely and mentions immunotherapy approval for NSCLC in the first-line setting. That note supplies context, but it does not establish the reason for termination beyond what it states, explain whether the endpoint could be evaluated, or document a decision process. The maximum tolerated dose endpoint definition refers to no more than 1 of 6 patients with dose-limiting toxicity. The registry does not explain how the stated enrollment related to that definition.
For safety, the treated group has 5 participants recorded at risk for serious adverse events and 4 recorded as affected. For other adverse events, 5 are recorded at risk and 5 as affected. Deaths are recorded as 0. These are descriptive counts in a small, uncontrolled group; they do not establish that the combination caused an event, nor do they permit a comparison with another treatment. Serious-event terms listed individually include atrioventricular block, lung infection, musculoskeletal and connective tissue disorder - Other, and respiratory, thoracic and mediastinal disorders - Other, each reported as 20.0%. The record does not say whether those categories overlap, and they should not be summed.
General statistical interpretation requires attention to both the amount of information and the way participants were selected and followed. Small groups yield imprecise estimates, and without a comparator, observed events or clinical outcomes cannot separate treatment effects from disease course, background risk, or other influences. The record does not report confidence intervals, adjusted estimates, or outcome analyses. No numerical estimate of efficacy or comparative safety can be inferred from the listed information. The posted data are best read as registry-level descriptions rather than evidence from a completed comparative assessment.
9. Statistical Methods Explained
The registry identifies this as a phase I/II, single-group study. It records allocation as not applicable and masking as none. Those details define the broad design: participants received the study combination, and the record does not describe randomized assignment or blinded treatment assessment. The statistical plan, including any specific estimation method or dose-selection algorithm, is not reported in the registry record. A design label does not by itself tell readers how every analysis was performed.
What does the primary endpoint measure?
The primary phase I endpoint is maximum tolerated dose. It is framed through a toxicity rule over up to 28 days: no more than 1 of 6 patients may experience a dose-limiting toxicity. The registry says toxicities are graded according to National Cancer Institute Common Toxicity Criteria version 4.0. In general, a rule of this kind translates a safety objective into a prespecified decision criterion. Applying it requires knowing which toxicities count as dose-limiting, how evaluability is determined, what dose levels are considered, and how decisions are made when observations are incomplete. Those operational details are not reported in the registry record.
The criterion should not be mistaken for a reported result. The registry provides no maximum tolerated dose value and does not state whether the criterion was reached. It records enrollment as 5, while its endpoint definition refers to 6 patients. The record does not explain this distinction or provide an endpoint analysis that resolves it. Without that information, readers cannot reconstruct the dose-finding conclusion from the endpoint definition alone.
Why does the design affect interpretation?
A single-group design can describe what happened among treated participants, but it does not directly estimate how outcomes would have differed under another treatment. In general, randomization helps balance measured and unmeasured characteristics across groups, while a concurrent comparator helps distinguish treatment-associated outcomes from changes that might occur without the study treatment. Neither feature is present in the registry description. Therefore, descriptive safety counts are not comparative risk estimates, and the record cannot establish a treatment effect for response, disease control, survival, or toxicity.
Masking is recorded as none. In general, knowledge of treatment assignment can influence outcome assessment or reporting, particularly for outcomes requiring judgment. The degree to which this matters depends on the outcome and assessment procedures. The registry does not report additional procedures that would clarify that issue, nor does it provide analyses of these outcomes.
How should the safety counts be read?
The serious adverse-event figures distinguish participants recorded as at risk from those recorded as affected. The treated group has 5 at risk and 4 affected for serious adverse events, while the other-adverse-event count is 5 at risk and 5 affected. Deaths are recorded as 0. These are counts, not adjusted estimates. General statistical principles caution that estimates from small groups can be unstable: a small change in observed events can substantially alter a rate, and uncertainty is difficult to characterize without a suitable interval or model. No confidence intervals or inferential comparisons are reported.
The serious-event terms each have a reported value of 20.0%. The registry does not report whether an individual participant could contribute to more than one term, nor does it describe the denominator used for each listed term beyond the group-level at-risk counts. The terms therefore should be read as separate registry listings, not added together into an overall event total. In general, overlapping event categories make summing category percentages inappropriate unless the record establishes that the categories are mutually exclusive.
What can the secondary outcomes establish?
The registry lists disease control rate, duration of response, overall survival, toxicity rates, and progression free survival as secondary outcomes, and records seven outcome measures. It reports no analyses. Definitions, assessment schedules, censoring rules, and analysis populations for those outcomes are not reported in the registry record. For time-to-event outcomes, general analysis commonly depends on follow-up duration and how censoring is handled; those details affect interpretation and are not available. No outcome estimate or uncertainty measure should be inferred from the outcome names alone.
Multiplicity refers generally to the increased chance of false-positive findings when many hypotheses are tested. The record lists several secondary outcomes, but it does not report a multiplicity adjustment or testing hierarchy. It would therefore be inappropriate to assume that any outcome was designated for confirmatory testing or that a particular error-control approach was used. The statistical analysis plan is not reported in the registry record.
What does the planning illustration mean?
The stated planning assumptions describe a hypothetical two-arm illustration: a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect defined as a stated fraction of an observed effect. In general, such calculations describe sample-size requirements under assumptions; they are planning illustrations, not observed power and not evidence that a trial had a particular probability of detecting an effect. They do not replace the actual trial design or analysis.
Those assumptions do not match the registry’s single-group design, and the record gives no comparative outcome analysis to interpret as an observed treatment effect. The dose-finding endpoint is also not the kind of two-arm comparison described in the planning assumptions. No planning estimate can establish what the terminated study would have shown. The registry does not report the trial’s own sample-size justification or a statistical plan linking that illustration to its conduct.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcome measures: disease control rate, duration of response, overall survival, toxicity rates, and progression free survival, alongside the primary maximum tolerated dose endpoint. It records seven outcome measures and zero analyses. Results for the secondary outcomes are not reported in the registry record. The statistical analysis plan, outcome hierarchy, and any distinction between exploratory and confirmatory analyses are not reported.
In general, testing multiple outcomes creates a multiplicity issue because the chance of obtaining an apparently notable result can increase as more hypotheses are examined. Researchers may address this through a prespecified testing order, adjusted significance thresholds, or other methods. The registry record does not say whether any such approach was planned or used. No claims about multiplicity control or statistical significance can be made from the outcome list alone.
Missing-data procedures are not reported in the registry record. The record does not describe how incomplete outcome assessments, withdrawal, loss to follow-up, or unevaluable participants were handled. Analysis populations, including any intention-to-treat or per-protocol definitions, are also not reported. These omissions matter because estimates can depend on who is included and how missing observations are treated. The record’s stated enrollment and termination status do not identify the analysis population or explain the endpoint’s evaluability.
For survival outcomes, censoring rules and follow-up summaries are not reported. For the dose-finding endpoint, the registry does not explain how the criterion referring to 6 patients was applied given the recorded enrollment of 5. These gaps prevent reconstruction of an analysis and limit the strength of conclusions that can be drawn from the registry record.
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 |
|---|---|---|---|
| Treatment (Plinabulin, Nivolumab) | 4 | 5 | 80.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Plinabulin, Nivolumab) | 0 of 5 |
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 |
|---|---|
| Treatment (Plinabulin, Nivolumab) | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Plinabulin, Nivolumab) |
|---|---|---|
| Atrioventricular block | Cardiac disorders | 1 of 5 |
| Lung infection | Infections and infestations | 1 of 5 |
| Musculoskeletal and connective tissue disorder - Other | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Plinabulin, Nivolumab) |
|---|---|---|
| Infusion related reaction | General disorders | 2 of 5 |
| Mucositis oral | Gastrointestinal disorders | 1 of 5 |
| Nausea | Gastrointestinal disorders | 1 of 5 |
| Lung infection | Infections and infestations | 1 of 5 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Musculoskeletal and connective tissue disorder - Other | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 5 |
| Hypertension | Vascular disorders | 1 of 5 |
Serious events with the highest arm-level rate: atrioventricular block (20.0%), lung infection (20.0%), musculoskeletal and connective tissue disorder - other (20.0%), respiratory, thoracic and mediastinal disorders - other (20.0%).
The registry records a single treatment group. For serious adverse events, 5 participants are listed as at risk and 4 as affected. For other adverse events, 5 are listed as at risk and 5 as affected. Deaths are recorded as 0. These figures describe what the registry reports for this group; they are not a comparison with another treatment and do not, on their own, establish that the study drugs caused the events.
The listed serious adverse-event terms are atrioventricular block, lung infection, musculoskeletal and connective tissue disorder - Other, and respiratory, thoracic and mediastinal disorders - Other. Each term is reported as 20.0%. The record does not clarify whether categories overlap, whether participants had multiple events, or how event terms were adjudicated. The term percentages should not be added together to create a total.
In general, adverse-event counts from a small group are descriptive and imprecise. They may be useful for identifying what was recorded during the trial, but they cannot establish comparative safety or quantify risk relative to a control. The registry does not report confidence intervals, event timing, severity breakdowns beyond the serious-event classification, or an analysis relating events to dose.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase I/II investigation of nivolumab with plinabulin in advanced non-small cell lung cancer. It specifies a single treatment group, the intended dosing schedule, a primary phase I dose-finding endpoint, and several secondary outcomes. The record also documents that the study terminated and that enrollment was 5. It provides limited adverse-event counts and lists serious-event terms. These registry entries describe the registered study and the information posted for it.
The record does not report a maximum tolerated dose, a dose-limiting-toxicity result, or analyses of disease control, response duration, survival, progression free survival, or toxicity rates. Therefore, the registry information does not establish whether the combination improved a clinical outcome, how its outcomes compare with another treatment, or whether a planned dose criterion was met. The outcome names are not outcome findings.
The single-group design is central to interpretation. Without a comparator, observed events cannot be separated from background risks or the course of disease, and clinical outcomes cannot be attributed to the combination through a randomized comparison. The absence of masking may also be relevant to outcome assessment in general, although the record does not provide detail on assessment procedures. The safety counts should be read as descriptive reports, not as comparative evidence.
The termination note states that the study stopped prematurely and mentions immunotherapy approval for NSCLC in the first-line setting. It does not provide a full account of the circumstances or say how termination affected each endpoint. The endpoint definition refers to 6 patients, while recorded enrollment is 5; the registry does not explain how that affected evaluation. This leaves the primary question unresolved in the posted record.
In general, an absent result is not evidence of no effect, and a reported event count is not proof of causation. The most defensible conclusion is limited: the registry describes the study’s intended question and conduct, but its posted information does not provide the analysis needed to answer the primary or secondary efficacy questions. It also does not support a comparative safety conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable because its main phase I question is a dose-finding question, while the registry record does not report the dose-finding result. The endpoint is defined through a toxicity boundary over up to 28 days, making the interpretation dependent on the operational dose-finding rules and on whether enough participants were evaluable. Those details are not reported. The stated endpoint criterion refers to 6 patients, whereas enrollment is recorded as 5, and the record does not explain the relationship.
The study also illustrates why design and outcome reporting must be read together. The single-group model can provide descriptive information about people who received the combination, but it does not provide a concurrent counterfactual. In general, a treatment outcome observed without a comparator cannot determine what would have happened under another treatment or no study treatment. This is especially important when the record contains no outcome analyses.
The safety information demonstrates the difference between a count and a comparative estimate. The registry reports the number at risk and the number affected for serious and other adverse events, along with selected serious-event terms. Those observations are clinically relevant descriptions of what was recorded, but they do not establish causation or relative safety. The small recorded enrollment and lack of uncertainty estimates further limit precision.
The record lists several secondary outcomes but reports zero analyses. That contrast highlights the importance of complete outcome reporting: an outcome label says what was intended for measurement, not what the study found. Statistical interpretation requires estimates, uncertainty, analysis populations, and sufficient detail on follow-up and outcome definitions. Those elements are not reported in the registry record.
Finally, the registry notes premature termination and gives contextual information about immunotherapy approval in the first-line setting, but does not provide a full account of the decision or its analytical consequences. Statistically, this makes it important to distinguish what is documented from what remains unknown. The trial record is informative about design and reporting limitations, but does not resolve the combination’s efficacy or comparative safety.
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 most consequential limitation is that the registry reports no analyses and no primary-endpoint result. The primary question concerned maximum tolerated dose, yet no dose estimate or conclusion about the dose-limiting-toxicity rule is posted. Secondary outcomes are named, but their results are not reported. The study’s termination means the intended assessment was not completed as planned, according to the endpoint population note.
Recorded enrollment is 5, while the endpoint definition specifies a criterion involving 6 patients. The registry does not explain whether the endpoint could be evaluated, how dose cohorts were managed, or whether the criterion was modified. The dose-escalation and dose-selection procedures are not reported, making it impossible to reconstruct the phase I method from the endpoint description alone.
The single-group design provides no randomized comparator. Consequently, the posted information cannot establish comparative efficacy or safety, and it cannot isolate the effects of nivolumab and plinabulin from one another. Masking is recorded as none. The record does not describe additional safeguards for outcome assessment.
Eligibility details, outcome definitions beyond the primary endpoint, assessment schedules, follow-up, censoring rules, analysis populations, missing-data handling, and a statistical analysis plan are not reported in the registry record. Nor does it report confidence intervals or adjusted estimates. These omissions limit assessment of precision, bias, and the methods used for any intended analysis.
The safety counts are descriptive and come from the treated group only. The registry does not clarify overlap among event terms or provide comparative estimates. The termination note gives context but not a full account of the decision or its impact on each outcome. These limitations mean the posted information is insufficient to draw efficacy conclusions or a comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer — NCT02846792.
- Registry record last updated 2019-03-04; status last verified 2019-02.
- Results first posted 2019-03-04.
- 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
NCT02846792 is a University of Washington phase I/II study of nivolumab with plinabulin for advanced non-small cell lung cancer. It used a single-group design with no masking and recorded enrollment of 5. The primary phase I endpoint was maximum tolerated dose, defined by a dose-limiting-toxicity criterion over up to 28 days. The registry lists disease control rate, duration of response, overall survival, toxicity rates, and progression free survival as secondary outcomes.
The study status is terminated. The record says the study stopped prematurely and notes immunotherapy approval for NSCLC in the first-line setting. It reports no analyses and no primary-endpoint result. Safety entries include 4 affected among 5 at risk for serious adverse events, 5 affected among 5 at risk for other adverse events, and 0 deaths. The posted information does not establish treatment efficacy or provide a comparative safety assessment.