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 Dose Escalation Trial of Intra-Tumoral Injection of NIS Measles Virus in Combination With Atezolizumab (NCT02919449), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of MV-NIS in Combination With Atezolizumab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02919449 |
| Phase | Phase 1 |
| Condition | Recurrent Non-Small Cell Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vyriad, Inc. |
| Results posted | Yes |
2. Clinical Question
The trial was intended to assess the maximum tolerated dose (MTD) and toxicity of intratumoral MV-NIS when given with atezolizumab in patients with recurrent and metastatic non-small cell lung cancer. Its primary endpoint was the MTD of MV-NIS in combination with atezolizumab, assessed over 28 days after MV-NIS administration for each dose cohort.
Population
Patients with recurrent and metastatic NSCLC. The registry condition is recurrent non-small cell lung cancer. Enrollment was 2, and the registry states that the study closed prematurely for administrative reasons.
Intervention
MV-NIS, an Edmonston-strain measles virus genetically engineered to produce NIS, was administered by intratumoral injection as a single dose on day 1. Atezolizumab was scheduled for day 15 and then every 3 weeks.
Comparator
There was a single treatment group combining MV-NIS and atezolizumab. No concurrent control group or randomized comparison is reported in the registry record.
Primary question
What maximum tolerated dose of intratumoral MV-NIS can be identified in combination with atezolizumab, with the primary assessment timeframe defined as 28 days after MV-NIS administration for each dose cohort?
This is a dose-escalation and safety question, not a randomized test of comparative efficacy. The registry record does not report an MTD value or a dose-limiting toxicity summary. It explicitly cautions that the very limited number of patients and short duration of study treatment do not allow meaningful conclusions from the available data.
3. Trial Design
The registry classifies this as a Phase 1 study with a single-group model, no masking, and allocation listed as not applicable. The planned treatment combined intratumoral MV-NIS with atezolizumab. MV-NIS was described as a single administration on day 1; atezolizumab was scheduled for day 15 and then every 3 weeks. The primary endpoint timeframe was 28 days after MV-NIS administration for each dose cohort.
The registry reports enrollment of 2 and a status of terminated. It states that the study was prematurely closed for administrative reasons. The start date was 2017-08-03, and the primary completion date was 2018-01-19. The record does not report the dose cohorts, the dose levels actually administered, how dose escalation was governed, or the reason for termination beyond administrative reasons.
With one treatment group, the study can describe observations among participants who received the combination, but it cannot estimate a randomized treatment contrast. There is no like-for-like control arm in the registry record. This matters because changes in outcomes cannot be attributed to one component of the combination by comparing treatment groups, and outcomes cannot be separated from the course of disease or other influences using a concurrent control.
The record lists one outcome measure and no analyses. It does not report a statistical analysis plan, an enrollment target, the number of participants planned for each dose cohort, or a sample-size justification. Those omissions prevent assessment of whether the enrollment matched a prespecified plan. The very small enrollment and the registry's own caution about short treatment duration place strong limits on any interpretation of observed safety or dose-finding information.
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 | MV-NIS and Atezolizumab |
|---|---|
| STARTED | 2 |
| COMPLETED | 0 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | MV-NIS and Atezolizumab |
|---|---|
| Withdrawal by Subject | 1 |
| Investigator decision | 1 |
Analysis population for the primary outcome, as defined in the registry: The study was prematurely closed for administrative reasons. The very limited number of patients (n=2) and short duration of study treatment does not allow any meaningful conclusions to be drawn from the available data.
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: A maximum of 21 patients were planned for this study, 2 patients were treated prior to the closure of the study. The study was closed for administrative reasons.
| Characteristic | Unit | MV-NIS and Atezolizumab |
|---|---|---|
| Participants analysed | 2 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 1 |
| 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 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of MV-NIS in Combination With Atezolizumab, measured over 28 days after MV-NIS administration for each dose cohort.
| 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 MV-NIS in combination with atezolizumab. The registry describes the objective as determining the MTD of intratumoral Edmonston-strain MV-NIS, genetically engineered to produce NIS, when used with the PD-L1 inhibitor atezolizumab. The assessment timeframe is 28 days after MV-NIS administration for each dose cohort.
General: Dose-escalation studies use a tolerability endpoint to guide decisions about which dose levels warrant further study. The MTD is intended to identify a dose boundary based on a protocol-defined assessment of toxicities. Its interpretation depends on the dose levels studied, the rules for classifying dose-limiting events, the observation window, and the escalation or de-escalation rules. These protocol details are not reported in the registry record, so the endpoint definition cannot be reconstructed beyond the stated objective and timeframe.
The registry record gives no numerical MTD result, dose-cohort outcome, or dose-limiting toxicity count. It also says that enrollment was very limited and treatment duration short, preventing meaningful conclusions from the available data. Thus, the endpoint's intended role is clear, but the posted record does not establish an MTD.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is the amount of information available. The registry reports enrollment of 2, describes premature closure for administrative reasons, and states that the small number of patients and short treatment duration do not allow meaningful conclusions. Those statements constrain interpretation regardless of the intended dose-escalation objective.
The primary endpoint is an MTD, but the registry does not report an MTD estimate or the dose-level observations needed to evaluate one. The record also does not give dose-limiting toxicity criteria, cohort sizes, or escalation decisions. Without those details, readers cannot tell from the posted results how the intended dose-finding process unfolded. The registry lists one outcome measure but no analyses.
There is no randomized comparison. The design is single-group, with MV-NIS and atezolizumab given in combination. Accordingly, the record cannot support a comparative estimate against another treatment or distinguish the separate contributions of the two agents. The absence of a comparator is a design feature, not evidence that any outcome was better or worse than it would have been under another treatment.
Safety reporting should also be read descriptively. The adverse-event figures indicate 2 participants at risk for other adverse events and 2 affected; for serious adverse events, 2 were at risk and 0 were affected. The record reports 0 deaths. These counts are observations in a very small enrolled group, not precise estimates of how often events would occur in a broader population. The registry does not list serious adverse-event terms, and the available record does not provide event-level detail or duration of follow-up beyond the stated primary endpoint timeframe.
No confidence intervals, p-values, or inferential analyses are reported in the registry record. General: A confidence interval expresses uncertainty around an estimate; with limited information, uncertainty can remain substantial even when a point estimate is available. Here, the registry does not provide a numerical primary-endpoint estimate to accompany such an interval. The absence of a reported statistical result should not be interpreted as evidence of no effect, no toxicity, or a particular dose being tolerable. The supported conclusion is narrower: the record documents a small, prematurely terminated dose-escalation study and does not report enough primary-endpoint information for a meaningful MTD conclusion.
9. Statistical Methods Explained
General: A single-group dose-escalation study differs from a randomized comparative trial. Its central task is to observe tolerability at planned dose levels and use prespecified rules to guide whether escalation, repetition, or stopping is appropriate. The registry record identifies the study as Phase 1 and dose escalation, but does not report the actual dose levels, cohort sizes, escalation rules, or toxicity criteria. Consequently, those elements cannot be evaluated from the registry record.
What does the primary endpoint represent?
The endpoint is the MTD of MV-NIS in combination with atezolizumab, assessed within 28 days after MV-NIS administration for each dose cohort. General: An MTD is not simply the highest dose administered. Its meaning depends on how toxicities are defined and attributed, what observation period is used, and what decision rule is applied to the observed events. A complete statistical interpretation would therefore need the protocol's definitions and dose-level results. Those are not reported in the registry record, and no MTD value is posted.
What can a single treatment group estimate?
General: A single-group design can describe the participants treated, the doses they received, and the events recorded during follow-up. It does not create a concurrent counterfactual group—that is, a group showing what would have happened to comparable participants under a different treatment. As a result, it cannot estimate a randomized between-treatment difference. In this study, MV-NIS and atezolizumab were combined, so a single group also cannot isolate the contribution of either component.
The registry records no randomized allocation and identifies the study as single group. The absence of a control is consistent with a dose-finding objective, but it limits what can be inferred about comparative outcomes. Any descriptive safety counts should therefore be understood as counts among the enrolled participants, not as comparative rates or causal effects.
How should the posted event counts be understood?
General: An event count is a description of what was observed during the recorded follow-up. It is not, by itself, a precise estimate of the probability of an event in a wider patient population. Precision depends on the amount of information, including the number of participants, the completeness and duration of follow-up, and how events are defined and collected. Here, enrollment was 2, and the registry itself warns that the limited number of patients and short treatment duration prevent meaningful conclusions.
The registry reports serious adverse-event counts and other adverse-event counts, but does not list serious-event terms. The record does not provide enough detail to assess event severity categories, timing, recurrence, or attribution. General: In a safety analysis, the distinction between serious and non-serious events is based on event definitions, not simply on whether an event occurred. A reader should not infer the absence of non-serious events from a zero serious-event count.
What do missing inferential results mean?
The registry lists one outcome measure and no analyses. It reports no numerical MTD, confidence interval, p-value, or dose-specific endpoint result. General: Inferential statistics quantify uncertainty or assess compatibility with a statistical model, but they cannot replace missing outcome data or an absent analysis plan. When estimates and uncertainty measures are not reported, the available record supports a descriptive account of design and recorded counts rather than a quantitative conclusion about the primary endpoint.
How should planning calculations be separated from trial findings?
General: A sample-size planning illustration asks how many participants might be needed under specified assumptions to detect an assumed effect. It is not a result observed in the trial, and it does not establish the probability that this study detected an effect. The registry record does not report a trial-specific sample-size justification. Any planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation is separate from the actual design and outcomes of this single-group trial. Such assumptions do not create a randomized comparison where none was conducted. A planning quantity should therefore not be read as evidence that the trial had adequate information for MTD determination.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure, the MTD of MV-NIS in combination with atezolizumab, and no analyses. It does not report a statistical analysis plan or identify additional primary or secondary hypotheses. A multiplicity adjustment, or a decision not to adjust, is not reported in the registry record.
General: Multiplicity arises when multiple outcomes, dose comparisons, time points, or statistical tests are examined. Repeated testing can increase the chance of a seemingly notable result arising by chance, so an analysis plan commonly specifies which outcomes are primary and how multiple comparisons will be handled. In a dose-escalation study, the dose-finding procedure itself also depends on prespecified rules. Here, those rules and any multiplicity strategy are not reported, so their appropriateness cannot be assessed.
The record states that the study was prematurely closed for administrative reasons, with enrollment of 2 and a short duration of treatment. It does not describe how missing or incomplete outcome data were handled, whether any participants discontinued treatment, or whether follow-up was complete for the primary endpoint. Missing-data methods are therefore not reported in the registry record. The record also does not specify an analysis population, such as whether the primary endpoint was to be assessed among all enrolled participants or only participants who received treatment.
General: The population included in an analysis affects the interpretation of results. A prespecified analysis population helps readers understand which participants contribute to each estimate and how deviations from planned treatment are handled. Without that information and without posted analyses, there is no basis for reconstructing a primary analysis or judging sensitivity to missing data. These reporting gaps add uncertainty to interpretation but do not justify assuming that any particular method was used.
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 |
|---|---|---|---|
| MV-NIS and Atezolizumab | 0 | 2 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| MV-NIS and Atezolizumab | 0 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| MV-NIS and Atezolizumab | 2 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MV-NIS and Atezolizumab |
|---|---|---|
| Chills | Infections and infestations | 2 of 2 |
| Viral illness | Infections and infestations | 2 of 2 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 2 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 2 |
| Nausa | Gastrointestinal disorders | 1 of 2 |
| Headache | Nervous system disorders | 1 of 2 |
The registry reports that 2 participants were at risk for serious adverse events and 0 were affected. For other adverse events, 2 were at risk and 2 were affected. The record reports 0 deaths. It does not list serious adverse-event terms.
These are descriptive counts from the enrolled group, not precise estimates of event frequency in a broader population. Enrollment was 2, and the registry states that treatment duration was short and the available data do not allow meaningful conclusions. With so few participants, the counts cannot establish that an event is rare or that an event would not occur with longer observation.
General: Serious adverse events and other adverse events are distinct reporting categories. A count of serious events does not capture every adverse event, and an event count alone does not show its timing, duration, severity, or relationship to treatment. The registry record does not provide event-level details for these counts. The zero serious-event count should therefore be read narrowly as no serious events recorded among the 2 participants at risk in the posted results, not as proof that serious toxicity is absent.
12. What the Result Does, and Does Not, Mean
The registry record supports a limited description of a Phase 1, single-group study intended to determine the MTD and toxicity of intratumoral MV-NIS combined with atezolizumab. The treatment schedule specified a single MV-NIS dose on day 1, followed by atezolizumab on day 15 and every 3 weeks. The primary endpoint timeframe was 28 days after MV-NIS administration for each dose cohort.
The record does not provide a numerical MTD, dose-specific outcome, or analysis of the primary endpoint. It reports enrollment of 2 and says the study was prematurely closed for administrative reasons. The record explicitly states that the very limited number of patients and short duration of study treatment do not permit meaningful conclusions from the available data. The safety counts should likewise be treated as descriptive observations in a very small group.
The results do not establish that a particular dose is tolerable, nor do they establish that the combination is safe or unsafe in a broader population. They also do not test whether the combination improves outcomes relative to another treatment: the study had no randomized comparator, and no comparative efficacy result is reported. The absence of a posted MTD or inferential analysis is not evidence that there was no effect or no toxicity; it means that the registry record does not report those findings.
General: A study's objective and its evidentiary contribution are not the same. A protocol may aim to answer a question, but the conclusions depend on the data collected, the analysis performed, and the precision of the results. In this case, the record documents the intended dose-finding question and the reason the available results are limited, but it does not establish a dose-finding conclusion. Interpretation should remain bounded by the posted design, counts, and explicit statement about the inability to draw meaningful conclusions.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a study objective and an estimable result. The stated objective was to determine an MTD for MV-NIS combined with atezolizumab, with a defined assessment timeframe. Yet the registry reports enrollment of 2, premature administrative closure, no analyses, and no MTD value. A clear endpoint does not guarantee that enough outcome information will be available to answer it.
The design also illustrates the role of the control group in defining the question a study can answer. A single-group dose-escalation study may be structured to describe tolerability across doses, but it does not estimate a randomized comparison with another treatment. Since the treatment combined MV-NIS and atezolizumab, the design also cannot separate the effects of the individual components. These boundaries follow from the study design, not from a judgment about the treatments.
General: Statistical precision is linked to the quantity and quality of information. Very limited enrollment and short follow-up can leave substantial uncertainty, especially for safety outcomes or dose-finding decisions that depend on observing events over a defined period. A zero count in a small group is not equivalent to evidence that an event cannot occur. Reporting the denominator, follow-up context, and event definitions is important for understanding what a count can and cannot show.
The registry's explicit caution is important: the limited number of patients and short duration do not permit meaningful conclusions. The record therefore offers a useful lesson in restraint. Statistical interpretation should distinguish the intended question, the information actually reported, and the conclusions that the data can support. In this case, the first is stated, but the record does not provide the primary-endpoint result needed for a meaningful answer.
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 limitations specific to this study are stated or apparent in the registry record. Enrollment was 2, and the study was prematurely closed for administrative reasons. The record itself says that the very limited number of patients and short duration of study treatment do not allow meaningful conclusions from the available data. These constraints apply to the primary dose-finding objective as well as to interpretation of the safety counts.
The registry does not report the dose levels, the number of participants assigned to each dose cohort, the escalation rules, or the criteria used to define dose-limiting toxicity. It does not provide a numerical MTD result or a dose-specific summary. These omissions mean that the intended dose-finding process cannot be evaluated from the posted record.
The study was single group, with no randomized comparator. The combination design also prevents separation of the respective contributions of MV-NIS and atezolizumab. The registry reports no analyses and does not provide confidence intervals, p-values, or an analysis population. It does not state how incomplete follow-up or missing endpoint data were handled.
The adverse-event information is limited to counts. Serious adverse-event terms are not listed, and event-level details are not reported. The record does not provide enough information to assess event timing, duration, attribution, or completeness of safety follow-up. The primary endpoint's 28-day timeframe is stated, but the record also describes treatment duration as short and does not report a longer-term outcome analysis.
These limitations should not be filled in by assumptions about the protocol or unreported analyses. The registry does not report a trial-specific sample-size justification, interim analyses, or a full statistical plan. The posted information supports a description of the design and limited safety counts, but not a reliable estimate of MTD or comparative treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose Escalation Trial of Intra-Tumoral Injection of NIS Measles Virus in Combination With Atezolizumab — NCT02919449.
- Registry record last updated 2023-07-21; status last verified 2022-01.
- Results first posted 2023-07-21.
- 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
NCT02919449 is a Phase 1, single-group dose-escalation study of intratumoral MV-NIS combined with atezolizumab in patients with recurrent and metastatic NSCLC. MV-NIS was scheduled as a single dose on day 1, with atezolizumab on day 15 and then every 3 weeks. The primary endpoint was the MTD of MV-NIS in combination with atezolizumab, assessed 28 days after MV-NIS administration for each dose cohort.
The registry reports enrollment of 2 and status as terminated, with premature closure for administrative reasons. It reports 0 serious adverse events among 2 at risk, other adverse events in 2 of 2 at risk, and 0 deaths. No MTD result or analyses are reported. The registry states that the limited enrollment and short treatment duration do not allow meaningful conclusions from the available data.