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 HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors (NCT02426892), a na phase 2 study. The primary outcome is Number of Participants With Overall Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02426892 |
| Phase | Phase 2 |
| Condition | Solid Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with HPV-16-positive incurable solid tumors. The registry lists the condition as solid tumors and describes the study goal as investigating cancer that had spread. It does not give further eligibility details or a fuller description of the analyzed population in the primary outcome entry.
Intervention
Participants received ISA101, an HPV-16 vaccine, with nivolumab. The registry describes ISA101 as investigational and says the combination with nivolumab was investigational. The vaccine was administered subcutaneously at 100 mcg for a total of 3 doses, starting on Day 1, at 3 to 4 weeks intervals. Nivolumab was administered intravenously at 3 mg/kg every 2 weeks beginning on day 8 after the first vaccine dose.
Comparator
There was no separate comparator group. The study model is single group, allocation is listed as NA, and masking is listed as NONE. The results therefore do not provide a randomized, like-for-like comparison with another treatment or with no study treatment.
Primary question
The primary endpoint was the number of participants with an overall response, defined using complete and partial responses under RECIST 1.1 criteria. Response was assessed at 11 weeks from start of treatment among evaluable subjects. The registry record does not report the number of participants who responded or the resulting response proportion, so the primary outcome cannot be quantified from the posted results.
3. Trial Design
This was a phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists allocation as NA and masking as NONE. All participants were assigned to the combination of ISA101 vaccination and nivolumab; the study did not include a concurrent control group. The registry status is COMPLETED, with a start date of 2015-12-23 and a primary completion date of 2021-11-30.
The registry enrollment entry is 33. The brief summary, however, says that up to 28 participants would be enrolled, and that all would take part at MD Anderson. These entries differ, and the record does not explain the discrepancy. The adverse-event summary separately lists 24 participants at risk for the treatment group. The registry does not explain how those counts relate to each other or to the participants included in the primary outcome analysis.
The regimen description specifies ISA101 at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab was given at 3 mg/kg every 2 weeks beginning on day 8 after the first vaccine dose. The description also says that Cycle 1 was 3 weeks and Cycles were 2 weeks, but the cycle description ends before the later detail is complete. The full treatment schedule beyond those details is not reported in the registry record.
The primary endpoint was overall response, with response assessed at 11 weeks from start of treatment among evaluable subjects. The registry lists progression-free survival, progression-free survival rates at 2 and 3 years, median overall survival, overall survival rates at 2 and 3 years, and adverse events as secondary outcomes. Their results are not reported in the registry record. The registry does not report the statistical analysis plan, target enrollment justification, interim analyses, or a description of how the planned study enrollment relates to the final enrollment entry.
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: 33 participants were registered, 9 participants screen fail (not treated, not eligible or inevaluable)
Overall Study
| Stage | ISA101 Vaccine and Nivolumab |
|---|---|
| STARTED | 24 |
| COMPLETED | 4 |
| NOT COMPLETED | 20 |
Reasons for not completing this period:
| Reason | ISA101 Vaccine and Nivolumab |
|---|---|
| Adverse Event | 2 |
| Lack of Efficacy | 17 |
| Withdrawal by Subject | 1 |
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: All participants that signed the consent.
| Characteristic | Unit | ISA101 Vaccine and Nivolumab |
|---|---|---|
| Participants analysed | 33 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 23 |
| Age, Categorical: >=65 years | Participants | 10 |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 24 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| 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 | 6 |
| Race (NIH/OMB): White | Participants | 25 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | participants | 33 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Overall Response Rate (ORR), measured over From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with overall response rate (ORR). The registry defines ORR as the sum of subjects with a complete response (CR) and partial response (PR) divided by the number of evaluable subjects at 11 weeks from start of treatment. This is a response-based endpoint: it classifies tumor change according to specified criteria rather than measuring how long participants remain alive or without disease progression.
Response was assessed using RECIST 1.1 criteria. A complete response is defined as disappearance of all target lesions; pathological lymph nodes, whether target or non-target, must have reduction in short axis to <10 mm. A partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters as the reference. These rules give the response categories a consistent operational definition.
In general, an objective response endpoint can describe whether measurable disease meets prespecified criteria for tumor shrinkage at an assessment time. The evaluable-subject denominator matters: a response proportion describes the analyzed participants, and it may not represent all enrolled participants if some are not evaluable. The registry record does not report the number of evaluable subjects, the number with CR, the number with PR, or the calculated ORR. It also does not report the approach to participants who lacked an assessment at the specified time. Consequently, the endpoint definition is available, but its observed result and precision are not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study as a phase II investigation of ISA101 plus nivolumab in patients with HPV-16-positive incurable solid tumors. Its single-group design means the posted results can describe outcomes among people treated in the study, but cannot by themselves separate treatment-associated outcomes from the natural course of disease, participant selection, or other factors. There is no concurrent comparator against which to estimate a relative treatment effect.
The primary outcome is defined as participants with complete or partial response at 11 weeks from start of treatment, among evaluable subjects. However, the registry record does not report the observed ORR, its component counts, or the number of evaluable participants. No numerical conclusion about the primary endpoint can therefore be drawn from the posted results. A defined endpoint is not itself evidence of a particular result.
The record includes an adverse-event summary for the ISA101 Vaccine and Nivolumab group. It lists 24 participants at risk, 11 affected in the serious-event count, 23 affected in the other-event count, and 20 deaths. These counts describe what the registry reports for that group; they do not establish whether an event or death was caused by study treatment. The record does not provide enough detail in these summary figures to characterize timing, duration, severity beyond the serious-event classification, or individual clinical circumstances.
Selected serious adverse-event terms are listed with 4.2% beside each: Acute kidney injury, lanine aminotransferase increased, Anemia, Aspartate aminotransferase increased, Aspiration, and Colonic obstruction. The registry spells the second listed term as “lanine aminotransferase increased.” These are selected terms, not a complete account of all events or an estimate of comparative risk. A single-group study cannot establish whether an event occurred more often than it would have in a comparable untreated or differently treated population.
The registry lists progression-free and overall survival outcomes, including median outcomes and rates at 2 and 3 years, but does not report their results. It also does not report confidence intervals, p-values, adjusted analyses, or an analysis population description beyond the primary endpoint’s reference to evaluable subjects. Estimates without precision information would be difficult to assess even if their point values were available. Here, the outcome values themselves are absent from the registry record.
Enrollment entries also require care: the registry lists 33 participants, while its brief summary describes enrollment of up to 28; the safety summary lists 24 at risk. These are distinct entries and the record does not reconcile them. The planned study size, the final enrolled group, the safety population, and the primary endpoint population should not be presumed to be identical.
9. Statistical Methods Explained
The registry record gives an endpoint definition and selected safety counts, but does not report a full statistical analysis plan or primary outcome analysis. General statistical concepts can help clarify what the stated endpoint would mean and what information is needed to interpret it, without supplying a missing result.
How an overall response endpoint is formed
In general, an overall response endpoint combines participants meeting the definition of complete response with participants meeting the definition of partial response. The registry says to divide that sum by the number of evaluable subjects. This makes the denominator central to interpretation: the response proportion applies to the subjects included as evaluable, not necessarily to every person enrolled. The record does not state the evaluable-subject count or the response counts, so neither the proportion nor its uncertainty can be established from the posted results.
RECIST 1.1 criteria make response categories depend on changes in target lesions and, for complete response, the stated lymph-node condition. Standardized criteria are useful because they reduce reliance on an informal judgment that a tumor has improved. They do not eliminate all measurement uncertainty: imaging assessments, missing assessments, and decisions about evaluability can still affect classification. The registry does not report details about assessment review, assessor independence, or how disagreements were handled.
What an estimate and confidence interval would convey
In general, a response proportion is an estimate of the fraction of an analyzed group that met the response definition. A confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. A confidence interval does not repair limitations of study design, such as the absence of a comparator, nor does it account automatically for bias from missing data or participant selection.
The registry record does not report a confidence interval for ORR, nor the underlying numerator and denominator needed to review the estimate. It also does not report a p-value or a prespecified hypothesis test for the primary endpoint. No inferential conclusion should be attributed to the record in the absence of those results. A planning illustration based on an observed effect, when presented, is a hypothetical planning exercise and not observed power or evidence that a study had a particular probability of detecting an effect.
Single-group design and causal interpretation
In general, a single-group study can describe outcomes in its participants and provide information about feasibility and observed events. Without a concurrent comparison group, it cannot isolate the effect of the intervention from other influences. Differences in disease characteristics, prior treatment, follow-up, or measurement can also complicate comparisons with people from other studies. Historical comparisons, if attempted, would require assumptions that are not established by the registry entries.
This design issue is separate from the statistical precision of a response estimate. Even a precisely estimated response proportion would describe this study group, not necessarily the result that would have occurred under another treatment. In the present record, the estimate itself is not reported, so neither its precision nor its relationship to a comparator can be assessed.
Time-to-event outcomes
The listed secondary outcomes include median progression-free survival, progression-free survival rates at 2 and 3 years, median overall survival, and overall survival rates at 2 and 3 years. In general, time-to-event analyses account for both the time until an event and participants whose event status is not observed during follow-up. A participant without a recorded event may be censored at the last known observation, rather than treated as if an event had occurred or as if follow-up continued indefinitely. Interpretation depends on the event definitions, follow-up, censoring rules, and analysis population.
The registry record does not report the numerical survival outcomes or the analysis methods used for them. It does not state how progression or death was defined for these analyses, how censoring was handled, or whether any adjustment was planned. Those details cannot be inferred from the outcome titles alone.
Reading safety counts
In general, a count of participants with an event is different from a count of event episodes: one participant can experience more than one event, and several participants can experience events with the same term. Percentages for event terms describe their reported frequency according to the registry’s accounting, but should not be interpreted as comparative risk without an appropriate comparison group and complete definitions of the denominator and event collection period. The listed 4.2% values are recorded for selected serious-event terms; the record does not give full event-level detail alongside them.
For this trial, the safety summary identifies 24 participants at risk and reports 11 with serious events, 23 with other events, and 20 deaths. Those are descriptive safety figures. The registry does not provide a control group, treatment-attribution results, or detailed follow-up context for interpreting those counts as causal effects.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates several outcomes or performs several statistical tests: the chance of at least one apparently notable result can increase as the number of tests grows. In general, a statistical plan may specify which outcome is primary, which analyses are secondary or exploratory, and whether any adjustment or testing hierarchy will be used. Such planning helps readers distinguish the principal question from additional analyses.
The registry lists ORR as the primary outcome and several secondary outcomes: median progression-free survival, progression-free survival rates at 2 and 3 years, median overall survival, overall survival rates at 2 and 3 years, and adverse events. The statistical approach to multiplicity, including whether tests were planned and how they would be interpreted, is not reported in the registry record. The record also does not report outcome analysis results or p-values that would permit assessment of any multiplicity procedure.
The endpoint definition refers to evaluable subjects, but the registry does not state how evaluability was determined, how missing response assessments were handled, or whether participants were included in the primary analysis according to a prespecified population rule. It does not report the number of participants with missing outcome data or reasons for missingness. These details matter because excluding participants with unavailable assessments can change the group represented by the estimate.
The registry enrollment entry is 33, the brief summary describes enrollment of up to 28, and the safety group lists 24 at risk. The record does not explain the difference or give a participant-flow account linking enrollment to endpoint and safety populations. The target population for the analysis and the disposition of participants are therefore not fully described.
Interim analyses, sample-size justification, and the formal statistical analysis plan are not reported in the registry record. Without those details, it is not possible to assess how the analysis was prespecified, how incomplete data were addressed, or how the primary and secondary outcome questions were prioritized in practice.
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 |
|---|---|---|---|
| ISA101 Vaccine and Nivolumab | 11 | 24 | 45.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ISA101 Vaccine and Nivolumab | 20 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ISA101 Vaccine and Nivolumab | 23 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | ISA101 Vaccine and Nivolumab |
|---|---|---|
| Acute kidney injury | Renal and urinary disorders | 1 of 24 |
| lanine aminotransferase increased | Investigations | 1 of 24 |
| Anemia | Blood and lymphatic system disorders | 1 of 24 |
| Aspartate aminotransferase increased | Investigations | 1 of 24 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
| Colonic obstruction | Gastrointestinal disorders | 1 of 24 |
| Dysphagia | Gastrointestinal disorders | 1 of 24 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
| Gastroparesis | Gastrointestinal disorders | 1 of 24 |
| Infections and infestations - Other, specify | Infections and infestations | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ISA101 Vaccine and Nivolumab |
|---|---|---|
| Fatigue | General disorders | 19 of 24 |
| Anemia | Blood and lymphatic system disorders | 17 of 24 |
| Nausea | Gastrointestinal disorders | 15 of 24 |
| Cough | Respiratory, thoracic and mediastinal disorders | 13 of 24 |
| Pain | General disorders | 13 of 24 |
| Constipation | Gastrointestinal disorders | 12 of 24 |
| Dysphagia | Gastrointestinal disorders | 10 of 24 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 10 of 24 |
| Fever | General disorders | 9 of 24 |
| Dry mouth | Gastrointestinal disorders | 8 of 24 |
Serious events with the highest arm-level rate: acute kidney injury (4.2%), lanine aminotransferase increased (4.2%), anemia (4.2%), aspartate aminotransferase increased (4.2%), aspiration (4.2%).
The registry safety summary names one group, ISA101 Vaccine and Nivolumab, with 24 participants at risk. It reports 11 participants affected in the serious-event count, 23 affected in the other-event count, and 20 deaths. These are participant counts in the posted safety summary; they are not counts of event episodes and do not, by themselves, indicate whether any event or death was caused by treatment.
The listed serious adverse-event terms include Acute kidney injury, lanine aminotransferase increased, Anemia, Aspartate aminotransferase increased, Aspiration, and Colonic obstruction. Each is listed with 4.2%. These are selected terms in the registry record, not a complete narrative of all safety findings. The record does not provide detailed timing, duration, outcome, or treatment-attribution information for each event term.
In general, safety counts from a single-group study describe what was observed in that study group. They cannot establish how the frequency would compare with another treatment or with no study treatment. The record does not provide a comparator safety group, and the 20 deaths should not be interpreted as treatment-related on the basis of this summary alone. The registry does not reconcile the 24 participants at risk with its enrollment entries of 33 and up to 28.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study examined ISA101 vaccination with nivolumab in patients with HPV-16-positive incurable solid tumors. It specifies a primary response endpoint based on complete and partial responses assessed using RECIST 1.1 criteria at 11 weeks from start of treatment. These details identify the clinical question and how the response categories were defined.
The record does not report the primary endpoint result. It gives no count of complete responses, partial responses, evaluable subjects, or overall responders, and no ORR estimate or confidence interval. The posted information therefore does not establish the magnitude or precision of the observed response outcome. The endpoint definition should not be mistaken for evidence of an outcome.
The single-group design supports descriptive reporting of participant outcomes but does not provide a randomized comparison. Even if an outcome estimate were available, it could not by itself establish what would have happened to similar patients under a different treatment or without the study regimen. Statistical precision and causal interpretation are separate: precision concerns uncertainty in an estimate, while causal interpretation concerns whether the observed outcome can be attributed to the intervention.
The safety summary reports serious-event and other-event participant counts, selected serious-event terms, and deaths. Those figures warrant descriptive reading only. They do not identify treatment causation, and there is no comparator group for estimating a relative safety difference. The record also does not provide the clinical context needed to interpret each death or event.
Several outcomes named as secondary measures, including progression-free and overall survival measures, have no reported results in the registry record. The record also leaves the enrollment discrepancy unresolved and does not describe the analysis populations or missing-data methods. Accordingly, the appropriate statistical conclusion is limited: the study’s design, endpoint definitions, and selected safety counts are recorded, but the primary efficacy result and a comparative treatment effect are not established by the posted information.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a clearly defined question and a reported answer. The registry specifies an ORR endpoint, describes complete and partial response criteria, and identifies the assessment time. Yet the registry record does not report the observed response counts or estimate. Readers can understand what was intended to be measured without being able to determine the measured result.
The single-group design is also important to interpretation. In general, it can describe outcomes in a defined cohort, but it does not create a direct estimate of how outcomes differ under another treatment. This limitation is about the comparison structure, not about whether the endpoint was measured consistently. A reader should not treat a descriptive outcome as a comparative treatment effect.
The record illustrates why population definitions matter. It lists 33 participants enrolled, describes up to 28 in the brief summary, and reports 24 at risk in the safety group. The record does not explain how these numbers relate to the evaluable population for ORR. Without a participant flow and analysis-population description, denominators can be difficult to reconcile and the scope of each result is less clear.
Safety summaries also require distinctions between participants and events, and between occurrence and causation. The adverse-event counts and selected terms describe reported observations in the study group; they are not comparative estimates. These distinctions are broadly relevant when interpreting early-phase, single-group investigations.
Finally, the listed secondary outcomes show that the clinical question extends beyond tumor response to progression, survival, and adverse events. Their absence from the reported results prevents a fuller statistical account of the study. Clear reporting of estimates, uncertainty, analysis populations, and missing-data handling would be necessary to assess those outcomes comprehensively.
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 in the registry record is that it does not report the primary ORR result. Although the endpoint, assessment timing, and response criteria are described, the record does not give the number of evaluable subjects or response counts. This prevents assessment of the observed response proportion and its statistical precision.
The study is listed as single group, with no comparator and no masking. The absence of a control group limits causal interpretation, while the lack of masking may be relevant to outcome assessment and other aspects of trial conduct. The record does not describe whether response assessments were independently reviewed or how measurement decisions were made.
The enrollment count is inconsistent across entries: the registry lists 33, while the brief summary says up to 28. The adverse-event summary lists 24 participants at risk. The registry does not explain these differences or provide participant disposition, so the relationship among enrollment, safety, and efficacy populations is unclear.
The record’s regimen description is incomplete after stating the cycle lengths, and it does not provide further detail about the complete treatment schedule. It also does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, missing-data handling, or analysis-population definitions beyond the primary endpoint’s reference to evaluable subjects.
Secondary outcomes for progression-free survival and overall survival are listed, but their results and analysis details are not reported in the registry record. Safety information is limited to summary counts and selected serious-event terms, without a comparator or detailed event-level context. These limitations constrain both the completeness of the statistical interpretation and the degree to which the posted information can support conclusions about outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors — NCT02426892.
- Registry record last updated 2023-04-18; status last verified 2022-12.
- Results first posted 2023-04-18.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT02426892, a completed phase II study sponsored by M.D. Anderson Cancer Center. It evaluates ISA101 vaccination with nivolumab in patients with HPV-16-positive incurable solid tumors. The study is single group, with allocation listed as NA and masking listed as NONE. The registry lists enrollment as 33; the brief summary says up to 28 participants, and the safety group lists 24 at risk.
The primary endpoint is the number of participants with ORR, defined from complete and partial responses under RECIST 1.1 criteria at 11 weeks from start of treatment among evaluable subjects. The primary response result is not reported in the registry record. Listed secondary outcomes include progression-free survival, overall survival, and adverse events, but their results are not reported. The safety summary reports 11 participants with serious events, 23 with other events, and 20 deaths in the treatment group; the record does not establish treatment causation.