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 GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L) (NCT01497665), a na phase 2 study. The primary outcome is Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01497665 |
| Phase | Phase 2 |
| Condition | Non-small Cell Lung Cancer (NSCLC) With Brain Metastases |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Angiochem Inc |
| Results posted | Yes |
2. Clinical Question
Population
People with non-small cell lung cancer (NSCLC) and brain metastases. The registry record lists this condition but does not report further eligibility details or participant characteristics.
Intervention
GRN1005 alone. The study purpose was to assess efficacy, safety, and tolerability in this population.
Comparator
There was no comparator group: the study is recorded as single group, with allocation listed as not applicable and masking as none.
Primary question
What was the overall objective response rate, combining intracranial and extracranial disease assessments, during the study period?
The primary endpoint was the number of participants with an overall objective response. A response was defined as complete response or partial response under modified overall RECIST v1.1. Intracranial lesions were assessed by Gd-MRI; extracranial lesions were assessed with contrast-enhanced CT or MRI of the chest, abdomen, and pelvis. The stated timeframe ran from enrollment through the end of the study period, defined as 1 year after the last participant was enrolled.
This is a within-group question, not a randomized comparison of GRN1005 with another treatment or with no treatment. Consequently, the registry record can frame what the study intended to measure, but it cannot establish a treatment difference against a concurrent control. The primary response count and response rate are not reported in the registry record, so the clinical question cannot be answered from the posted primary outcome information.
3. Trial Design
GRABM-L was a phase II, multicenter, open-label study of GRN1005 in NSCLC patients with brain metastases. The registry lists a single-group model and an enrollment of 16 participants. The intervention arm is described as GRN1005 alone. Allocation is listed as not applicable, and masking as none; the design therefore has no randomized comparator arm or blinded treatment assignment recorded.
The study’s stated purpose was to assess efficacy, safety, and tolerability. Its primary outcome was overall objective response, including both intracranial and extracranial disease. Secondary outcomes listed in the registry were adverse events as a measure of safety and tolerability, duration of overall objective response, duration of overall progression-free survival, and six-month overall survival. The record lists five outcome measures in total, but it does not report analyses for them.
The study start is recorded as 2011-11, and primary completion as 2013-01. Its status is terminated. The reason for termination, the actual last-participant enrollment date, and further details about study conduct are not reported in the registry record. The primary outcome timeframe was described as extending from enrollment through the end of the study period, which was defined as 1 year after the last patient was enrolled.
Because this is a single-group study, any observed outcome would describe participants treated in this study rather than a contrast with an untreated or alternative-treatment group. The registry record does not describe a control strategy or a randomized allocation process. It also does not report eligibility criteria beyond the stated disease population, participant baseline characteristics, or details of the statistical analysis plan.
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 | GRN1005 Alone |
|---|---|
| STARTED | 16 |
| Completed Effifcacy Assessment | 10 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
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: 1. Safety population (all patients): 16 2. Efficacy population (defined as the number of patients who had ≥1 intracranial lesions followed as target or non-target lesions, and who were evaluated by Overall RECIST v.1.1):10
| Characteristic | Unit | GRN1005 Alone |
|---|---|---|
| Participants analysed | 16 | |
| Age, Continuous | years | 57.2 (SD 5.91) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 6 |
| Region of Enrollment: United States | participants | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis, measured over upon enrollment through end of study period (1 year after last patient is enrolled).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with an overall objective response, with the outcome title expressing this as the overall (intracranial and extracranial) objective response rate. The response definition combines complete response and partial response. A complete response required disappearance of all target and non-target lesions. A partial response required a >=30% decrease in the sum of the longest diameters of target lesions, with non-target lesions stable or decreased. Stable disease and progressive disease were also defined in the registry using modified overall RECIST v1.1 criteria.
Intracranial lesions were evaluated by Gd-MRI, while extracranial lesions were evaluated by contrast-enhanced CT or MRI of the chest, abdomen, and pelvis. Combining assessments across both locations makes the endpoint relevant to the stated population, whose disease includes brain metastases as well as NSCLC. The measure is a participant count: it records how many participants met the response definition, rather than how large a change occurred on average.
Objective response is used as a way to describe tumor change according to prespecified imaging criteria. However, a response count alone does not describe how long a response lasted or whether it was attributable to treatment. The registry separately listed duration of overall objective response and other secondary outcomes, but their results are not reported in the registry record. The primary response count and rate are also not reported, so the endpoint’s observed result and its precision cannot be assessed from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically focused primary outcome: overall objective response across intracranial and extracranial lesions. It gives the assessment methods, response categories, and intended observation timeframe. It does not, however, report the number of participants who achieved complete or partial response, an overall response rate, or an uncertainty estimate for that outcome. The registry record lists zero analyses. Without the primary outcome result, the stated efficacy question remains unanswered by the posted results.
The enrollment was 16, and the study was single group. The enrollment figure indicates the recorded study size; it is not itself evidence about the frequency of response. Nor can the size of any treatment effect be inferred from a study purpose, endpoint definition, or safety count. The record contains no concurrent comparator for estimating a treatment difference, and it does not report a comparison against an external reference group.
The safety information reports that 9 of 16 participants in the GRN1005 Alone group were affected by serious adverse events and that 16 of 16 were affected by other adverse events. The record also lists serious adverse-event terms with percentages. These entries describe the reported event experience in this group; they do not establish that GRN1005 caused every event. The registry does not report deaths in the adverse-event group entry. The reason the study was terminated is also not reported in the registry record.
Precision cannot be judged for the primary endpoint because its result and confidence interval are absent. A confidence interval, in general, communicates the uncertainty around an estimated quantity; it does not repair the absence of an estimate. Likewise, a p-value would address a specified statistical test, but no primary analysis or p-value is reported. No conclusion about whether an observed response frequency differs from a benchmark can be drawn because no benchmark or such analysis is reported.
Any sample-size figures associated with planning should be read as illustrations, not as observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and fractions of an observed effect. They do not turn this single-group study into a randomized comparison, and they do not substitute for the missing primary outcome analysis. The available record supports description of the study design and reported adverse-event counts, but not an estimate of primary efficacy or a comparative treatment effect.
9. Statistical Methods Explained
The record describes a phase II, open-label, single-group study. Those design features determine what kinds of statistical statements would be relevant. With one group and no randomized comparator, the direct study result would be a description of outcomes among participants receiving GRN1005. A treatment contrast against another group is not available from the recorded design. Open-label status means masking is listed as none; the registry does not explain whether or how that affected assessment procedures.
What does the response endpoint count?
The endpoint is a participant count based on an imaging response classification. Complete response and partial response both count toward overall response; stable disease and progressive disease do not meet the stated overall response definition. The record describes different imaging approaches for intracranial and extracranial lesions and uses modified overall RECIST v1.1 criteria. This makes the endpoint a categorical outcome for each participant: a participant either meets the response definition or does not. The registry does not report individual classifications or the aggregate number meeting the definition.
For a binary outcome, a response proportion is commonly calculated from the number with the event and the number assessed. That is general statistical context, not a reported calculation for this study. The primary result is presented in the record as a number of participants, but the response numerator and analysis denominator are not reported in the registry record. The enrollment of 16 should not automatically be treated as the number assessed for the primary endpoint, because the record does not state that all enrolled participants were included in that analysis.
How should uncertainty be understood?
General statistical interpretation uses an uncertainty interval, such as a confidence interval, to show how much imprecision accompanies an estimated response proportion. A narrow interval would indicate greater precision than a wide interval, under the method’s assumptions. The registry record does not report a response estimate or confidence interval, so neither the response frequency nor its precision can be evaluated. A significance test also requires a defined comparison or null hypothesis. No primary analysis is reported, and there is no concurrent comparator in the recorded design.
Small study size can make descriptive estimates imprecise; this is a general statistical consideration, not an estimate of precision for this trial. The actual precision depends on the observed response count and analysis method, neither of which is reported. A planning calculation is different from an observed result. Any planning illustrations use the stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Such figures are hypothetical planning quantities, not observed power, and the two-arm planning assumptions do not describe the single-group trial design.
What does the event count mean?
The adverse-event entries are counts of participants affected, with separate entries for serious and other adverse events. These are not necessarily counts of distinct events: a participant may experience more than one event, and the registry does not report event-level totals or whether categories overlap. In general, serious adverse events and other adverse events are different reporting groupings; an event’s appearance in a registry listing is not, by itself, proof that the intervention caused it. The record gives no causal attribution details for the listed terms.
Statistical analysis also depends on the population analyzed and handling of incomplete data. Those details are not reported in the registry record. It is not stated whether the primary outcome was analyzed in all enrolled participants, only participants with evaluable scans, or another defined population. Missing-data methods, censoring rules for time-to-event secondary outcomes, and any sensitivity analyses are not reported. These omissions limit reproducibility and make it impossible to determine how the stated endpoint would have been analyzed in practice.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and several secondary outcomes, including adverse events, duration of objective response, duration of progression-free survival, and six-month overall survival. It does not report a statistical analysis plan describing how results across these outcomes would be interpreted together. In general, testing multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance; methods such as a prespecified hierarchy or adjustment can address that issue. Whether any such approach was planned or used is not reported in the registry record.
The record lists zero analyses. It therefore does not report a primary outcome analysis, secondary outcome analyses, p-values, confidence intervals, or an approach to multiple testing. There is no basis in the posted results for identifying which outcomes, if any, were considered confirmatory or exploratory beyond their registry labels.
Missing-data handling is also not reported in the registry record. The number of participants with evaluable primary endpoint assessments, the treatment of missing or unevaluable scans, and the analysis population are not specified. The enrollment of 16 does not establish how many participants contributed to each outcome. For duration outcomes, censoring rules and the handling of participants without an observed event are not described. Details of interim analyses, if any, are not reported in the registry record.
These gaps matter because outcome definitions alone do not show how participants with incomplete follow-up entered the analysis, or whether interpretation accounted for the range of outcomes assessed. The registry does not provide enough information to reproduce an analysis or assess whether the reported outcome set reflects a prespecified statistical strategy.
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 |
|---|---|---|---|
| GRN1005 Alone | 9 | 16 | 56.2% |
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 |
|---|---|
| GRN1005 Alone | 16 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | GRN1005 Alone |
|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 3 of 16 |
| Neutropenia | Blood and lymphatic system disorders | 3 of 16 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 16 |
| Dysphagia | Gastrointestinal disorders | 1 of 16 |
| Vomiting | Gastrointestinal disorders | 1 of 16 |
| Mucosal inflammation | General disorders | 1 of 16 |
| Lung infection | Infections and infestations | 1 of 16 |
| Pneumonia | Infections and infestations | 1 of 16 |
| Fall | Injury, poisoning and procedural complications | 1 of 16 |
| White blood cell count decreased | Investigations | 1 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GRN1005 Alone |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 7 of 16 |
| Fatigue | General disorders | 6 of 16 |
| Neuropathy peripheral | Nervous system disorders | 6 of 16 |
| Leukopenia | Blood and lymphatic system disorders | 4 of 16 |
| Diarrhea | Gastrointestinal disorders | 4 of 16 |
| Nausea | Gastrointestinal disorders | 4 of 16 |
| Oedema peripheral | General disorders | 4 of 16 |
| Mucosal inflammation | General disorders | 4 of 16 |
| Dehydration | Metabolism and nutrition disorders | 4 of 16 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 4 of 16 |
Serious events with the highest arm-level rate: febrile neutropenia (18.8%), neutropenia (18.8%), thrombocytopenia (6.2%), dysphagia (6.2%), vomiting (6.2%).
In the GRN1005 Alone group, 16 participants were listed as at risk for serious adverse events, and 9 were listed as affected. For other adverse events, 16 were listed as at risk and 16 as affected. These are participant counts, not totals of individual events. The registry also identifies the following serious adverse-event terms and reported percentages: febrile neutropenia, 18.8%; neutropenia, 18.8%; thrombocytopenia, 6.2%; dysphagia, 6.2%; vomiting, 6.2%; and mucosal inflammation, 6.2%.
The terms are event categories, and the record does not say whether a participant could appear in more than one category. The listed percentages should therefore not be added together to estimate a total. The registry does not report additional details such as event timing, duration, severity grades, outcomes, or causal attribution. A serious adverse event is not automatically an event caused by the study intervention; the posted counts describe reported events among participants in the group.
The adverse-event entry does not provide a death count. The registry record also does not explain why the study was terminated. These safety figures can describe what was recorded in the group, but they do not establish comparative safety because the study has no control group.
12. What the Result Does, and Does Not, Mean
The record establishes that GRABM-L was a phase II, multicenter, open-label, single-group study of GRN1005 alone in NSCLC patients with brain metastases, with enrollment of 16 and terminated status. It defines an overall objective response endpoint using intracranial and extracranial imaging assessments and provides a set of serious adverse-event counts and terms. These registry entries describe the study’s design and some of its posted safety information.
The primary efficacy result is not reported in the registry record. There is no posted response count, response rate, confidence interval, or primary statistical analysis. As a result, the record does not show how many participants met the response criteria, how precise an estimate would be, or whether any comparison or statistical test was performed. The absence of a reported result should not be interpreted as a result of zero responses or as evidence of no effect.
The single-group design also limits what a result could establish. Even if an outcome estimate were available, it would describe the observed participants in this study rather than estimate a randomized difference from another treatment. Without a comparator, differences attributable to treatment cannot be separated from other explanations using this record alone. The record does not report details needed to evaluate the analysis population, missing outcomes, or the handling of secondary endpoints.
The adverse-event counts show that events were recorded among participants, including serious events and other events. They do not by themselves establish that GRN1005 caused those events or how its safety compares with another option. The termination status is recorded, but the reason for termination is not reported.
In statistical terms, the registry supports a description of intended measurement and reported event counts, not a conclusion about efficacy or comparative safety. The primary question remains unresolved in the posted results.
13. Why This Trial Matters Statistically
This trial illustrates why the design and completeness of a registry record matter when interpreting clinical outcomes. The primary endpoint is defined in detail: it combines intracranial and extracranial assessments, specifies imaging methods, and sets response categories under modified overall RECIST v1.1. That level of endpoint definition clarifies what the study intended to count. However, a clearly defined endpoint is not the same as a reported result.
The study’s single-group, open-label structure also determines the scope of statistical inference. A within-group response count could describe outcomes among enrolled participants, but without a concurrent comparator it would not provide a randomized estimate of difference between treatments. This distinction is important when reading any outcome claim: an endpoint can be clinically relevant while the design still limits causal interpretation.
The record additionally shows why analysis details are needed alongside outcome definitions. The primary response count, analysis denominator, uncertainty estimate, and statistical analysis are not reported. The record lists secondary outcomes, but does not provide analyses or explain missing-data handling or multiplicity strategy. Without those elements, readers cannot assess precision, reproduce analyses, or understand how results across outcomes were interpreted.
Finally, safety counts are informative as descriptions of recorded events but are not comparative evidence. Their meaning depends on event definitions, attribution, follow-up, and the population assessed. The record provides some counts and serious-event terms, but not the detail needed to assess causality or compare event rates with another group. Taken together, the study is statistically important as an example of how endpoint specification, design, outcome reporting, and analysis transparency jointly shape what can be concluded.
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 trial constrain interpretation of the registry record. The most direct is that the primary objective response result is not reported. There is no response count or rate, and the record lists zero analyses. The intended endpoint and its assessment criteria are described, but the posted record does not show the observed outcome or its precision.
The single-group design has no concurrent control. It can support description of outcomes within the treated group but cannot directly estimate a randomized treatment difference. The study is open label, with masking listed as none. The registry does not report further information about how imaging assessments were conducted or whether any independent review was used.
The recorded enrollment is 16, but the number assessed for the primary outcome is not reported. The analysis population, participant characteristics, handling of unevaluable scans, and missing-data methods are not reported in the registry record. These gaps prevent assessment of whether all enrolled participants contributed to each outcome.
The study status is terminated, but the reason for termination is not reported. The record also does not provide an actual last-enrollment date or more detail on follow-up. Although it lists secondary outcomes, it does not report their results, analysis methods, or any approach to multiplicity. Adverse-event counts and terms are available, but timing, event-level totals, causal attribution, and death counts are not reported in the adverse-event entry. These limitations restrict both efficacy interpretation and detailed safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L) — NCT01497665.
- Registry record last updated 2019-01-22; status last verified 2019-01.
- Results first posted 2015-12-14.
- 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
GRABM-L, registered as NCT01497665, was a phase II, multicenter, open-label, single-group study of GRN1005 alone in NSCLC patients with brain metastases. Enrollment was 16. The study started in 2011-11, reached primary completion in 2013-01, and is listed as terminated.
The primary outcome was overall objective response across intracranial and extracranial disease, assessed using modified overall RECIST v1.1. The registry lists secondary outcomes for adverse events, response duration, progression-free survival duration, and six-month overall survival. The primary response result and analyses are not reported in the registry record.
The adverse-event entry lists 9 of 16 participants affected by serious adverse events and 16 of 16 affected by other adverse events. The reason for termination, statistical analysis details, missing-data methods, and analysis populations are not reported in the registry record.