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 A Study of IMC-CS4 in Subjects With Advanced Solid Tumors (NCT01346358), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01346358 |
| Phase | Phase 1 |
| Condition | Neoplasms |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 52 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced solid tumors that were refractory to standard therapy or for which no standard therapy was available. The primary pharmacokinetic population was defined as enrolled participants who received at least one dose and had evaluable Cmax data.
Intervention
IMC-CS4, a monoclonal antibody targeting the CSF-1 receptor, was administered by intravenous infusion. The registry describes weight-based and non-weight-based dosing cohorts, including weekly and every-two-week schedules.
Comparator
There was no randomized control group. The registry classifies allocation as non-randomized and the model as sequential. The listed dose cohorts therefore should not be treated as like-for-like comparison arms.
Primary question
The primary endpoint was the pharmacokinetic maximum concentration, or Cmax, of IMC-CS4. The question was how the concentration measure was characterized at specified sampling times after dosing. Numerical Cmax results are not reported in the registry record.
This is a pharmacokinetic and safety-focused phase 1 study, rather than a randomized comparison of clinical benefit. Its stated purpose was to establish the safety profile and characterize the pharmacokinetic profile of IMC-CS4 in this population. The record also names selection of a recommended phase 2 dose and assessment of anti-IMC-CS4 antibodies as secondary outcomes. It does not report comparative treatment effects, nor does it establish that differences between dose cohorts are caused by dose. Sequential, non-randomized cohorts can help describe experience across dosing schedules, but differences in their observed characteristics or outcomes would not, by themselves, provide a controlled estimate of a dose effect.
3. Trial Design
This was a phase 1 study of IMC-CS4 in participants with advanced solid tumors refractory to standard therapy or for which no standard therapy was available. The registry lists the study as completed, with an enrollment of 52. The listed start date is 2011-06-15 and the primary completion date is 2018-05-31. Enrollment does not necessarily equal the number with evaluable pharmacokinetic data or the number included in each safety analysis.
The allocation is classified as non-randomized, masking as none, and the model as sequential. The study therefore does not provide a randomized, masked comparison between IMC-CS4 and a control treatment. It describes multiple dosing cohorts instead: Part A used weight-based schedules, while Part B used non-weight-based schedules. The listed regimens include weekly dosing and an every-two-week schedule. The detailed rules for moving between dose levels or opening expanded cohorts are not reported in the registry record.
The primary outcome was Cmax, expressed in micrograms per milliliter and summarized as a geometric mean with geometric coefficient of variation. The recorded sampling schedule included predose and post-dose assessments on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, and Cycle 3 Day 1. The primary population was participants who received at least one dose and had evaluable Cmax data. The registry lists seven outcome measures and no analysis entries. Further details of the analysis methods, cohort-specific evaluable populations, and handling of participants without evaluable measurements are not reported in the registry record.
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: Completers included participants who died from any cause or disease progression and participants who were alive and on study (either on study treatment or in long term follow-up) at study conclusion.
Only the first 6 of 9 groups are shown.
Overall Study
| Stage | Cohort 1 (2.5 Milligram Per Kilogram (mg/kg) QW) | Cohort 2 (0.3 mg/kg QW) | Cohort 3 (0.6 mg/kg QW) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 5 (1.25 mg/kg QW) |
|---|---|---|---|---|---|---|
| STARTED | 6 | 4 | 3 | 6 | 5 | 5 |
| COMPLETED | 4 | 3 | 2 | 5 | 4 | 3 |
| NOT COMPLETED | 2 | 1 | 1 | 1 | 1 | 2 |
Reasons for not completing this period:
| Reason | Cohort 1 (2.5 Milligram Per Kilogram (mg/kg) QW) | Cohort 2 (0.3 mg/kg QW) | Cohort 3 (0.6 mg/kg QW) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 5 (1.25 mg/kg QW) |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 1 | 0 | 1 | 1 | 0 | 2 |
| Adverse Event | 1 | 0 | 0 | 0 | 1 | 0 |
| Non-Compliance | 0 | 0 | 0 | 0 | 0 | 0 |
| Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of study drug and have evaluable PK data for Cmax.
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 enrolled participants
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | Cohort 1 (2.5 Milligram Per Kilogram (mg/kg) QW) | Cohort 2 (0.3 mg/kg QW) | Cohort 3 (0.6 mg/kg QW) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 5 (1.25 mg/kg QW) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 4 | 3 | 6 | 5 | 5 | |
| Age, Continuous | Years | 58.3 (SD 6.22) | 63.3 (SD 1.71) | 65.0 (SD 4.58) | 63.5 (SD 12.57) | 60.8 (SD 13.99) | 51.6 (SD 12.62) |
| Sex: Female, Male: Female | Participants | 3 | 1 | 2 | 1 | 4 | 2 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 1 | 5 | 1 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 4 | 3 | 5 | 5 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 4 | 3 | 3 | 5 | 5 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Region of Enrollment: United States | Participants | 6 | 4 | 3 | 6 | 5 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4, measured over Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | Microgram/milliliters (µg/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum concentration of IMC-CS4, abbreviated Cmax. It is a pharmacokinetic measure: it describes the highest measured concentration of a drug in the sampled blood after administration. The registry specifies the unit as micrograms per milliliter and reports that the endpoint was to be summarized using a geometric mean and geometric coefficient of variation. Measurements were scheduled at predose and at specified post-dose times across Cycle 1 and Cycle 3.
As a general statistical concept, pharmacokinetic concentration measures help characterize how drug exposure changes over time after dosing. Cmax can describe the peak concentration observed under a particular dose and schedule; it is not itself a measure of tumor response, survival, or clinical benefit. A geometric mean is often used for positive concentration measurements when values are better understood on a multiplicative scale. The geometric coefficient of variation describes relative dispersion on that scale, rather than spread in the original units. These are general interpretations of the statistical measures, not a claim about the pattern of results in this study.
The registry defines the analysis population as enrolled participants who received at least one dose and had evaluable Cmax data. It does not report numerical Cmax estimates, variability values, or a comparison between dose cohorts. Those results, and the number of participants contributing measurements at each sampling time, are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a phase 1 pharmacokinetic study, with dosing organized into non-randomized sequential cohorts. The primary endpoint is Cmax, measured at specified times after dosing and summarized using a geometric mean and geometric coefficient of variation. This design and endpoint indicate that the main statistical focus was characterization of drug concentration, alongside safety-related outcomes, rather than estimation of a randomized treatment effect.
The available record does not include numerical Cmax results. It therefore does not show the estimated peak concentrations, their variability, or how those measures differed among the listed dose schedules. Without those estimates and their uncertainty, the precision of the pharmacokinetic findings cannot be assessed from the registry record. No confidence intervals or other uncertainty intervals for Cmax are reported there. A confidence interval, as a general statistical concept, gives a range of values compatible with the data and analysis under stated assumptions; it does not replace the estimate itself.
The sequential, non-randomized allocation is important when interpreting any differences across cohorts. Participants were not assigned at random to comparable treatment groups, and there was no listed control arm. Cohort differences may reflect factors beyond the dose schedule, and the record does not support interpreting between-cohort contrasts as causal treatment effects. The study's stated aim of establishing a safety profile and characterizing pharmacokinetics should not be confused with a controlled test of efficacy.
Safety information is reported by cohort, including counts of participants affected by serious and other adverse events and counts of deaths. These are descriptive event summaries. They do not by themselves establish whether an event was caused by IMC-CS4, and the registry record does not supply the event-level context needed to evaluate causality or timing. The listed serious-event terms should likewise be read as reported terms, not as evidence that a particular dose caused them.
The registry lists seven outcome measures but no analysis entries. Details such as statistical models, adjustment for repeated measurements, confidence-interval procedures, and missing-data handling are not reported in the registry record. As a result, the record supports a description of the planned endpoint, schedule, and cohort structure, but not a quantitative assessment of the primary pharmacokinetic findings or a claim that one dose schedule performed better than another.
9. Statistical Methods Explained
What does Cmax measure?
Cmax is the maximum observed concentration of a drug in the sampled blood after administration. In this study, the registry identifies it as the primary pharmacokinetic outcome for IMC-CS4. Measurements were scheduled before dosing and at specified post-dose times on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, and Cycle 3 Day 1. Such sampling is intended to characterize concentrations over a dosing course, but a scheduled measurement is not necessarily available for every participant or every time point. The numbers of evaluable observations at individual times are not reported in the registry record.
Why use a geometric mean?
As a general statistical explanation, a geometric mean is suited to positive measurements that vary multiplicatively, as concentration data often can. It summarizes the central level after accounting for multiplicative rather than additive variation. The geometric coefficient of variation describes relative variability on that scale. It is not the same as a standard deviation in the original measurement units. The registry specifies these summaries for Cmax, but numerical estimates and dispersion values are not reported in the registry record. The basis for any transformation, treatment of values below assay limits, or calculation details is also not reported there.
What does the sequential design imply?
The registry classifies the model as sequential and the allocation as non-randomized. In general, sequential dose cohorts may be used to gather experience at different dose levels or schedules as a study proceeds. The precise escalation and cohort-opening rules for this study are not reported in the registry record, so the design label alone does not establish how dose decisions were made. Because participants were not randomized to a concurrent control group, the cohorts do not constitute a like-for-like treatment comparison. Descriptive differences in pharmacokinetic measures or adverse events should not be interpreted as unbiased estimates of the effect of changing dose.
The record describes weight-based dosing in Part A and non-weight-based dosing in Part B. The specific regimens listed include 2.5 mg/kg once weekly, 0.3 mg/kg once weekly, 0.6 mg/kg once weekly, 1.25 mg/kg every two weeks, and 1.25 mg/kg once weekly. Part B includes 100 mg once weekly, 100 mg once weekly on weeks 1, 2, 4 and 5, and 150 mg once weekly. These descriptions identify the regimens, but the registry does not report a formal statistical comparison among them.
How should uncertainty be assessed?
A confidence interval is, in general, an interval estimate that conveys uncertainty around an estimated quantity under a statistical model and its assumptions. It is most informative when reported alongside the estimate and when the analysis population and method are clear. The registry record does not report Cmax confidence intervals, standard errors, or other uncertainty intervals. It also contains no analysis entries. This absence means that the registry record does not allow assessment of precision for the primary endpoint; it does not establish that no analyses were performed outside the recorded results.
Pharmacokinetic data can include repeated observations from the same participant. As a general statistical matter, repeated measurements are correlated, so methods that account for within-participant dependence may be needed for some comparisons or models. The registry specifies the sampling schedule and a geometric summary, but it does not report whether a repeated-measures model or another approach was used. The model, if any, and its assumptions are not reported in the registry record.
What is over-dispersion, and is it relevant?
As a general concept, over-dispersion occurs when count data vary more than a simple statistical model assumes. It can lead to uncertainty estimates that are too narrow if the extra variability is ignored. The posted registry information does not identify an over-dispersion model or a count-based primary endpoint. Cmax is a concentration measure, so over-dispersion is not the defining issue for the stated primary endpoint. Whether any count outcomes were analyzed with methods that account for extra variability is not reported in the registry record.
How do planning calculations differ from study findings?
Sample-size calculations are planning illustrations, not observations from participants and not evidence of achieved power. The registry describes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a stated fraction of an observed effect. Those assumptions do not convert this non-randomized sequential study into a two-arm randomized comparison. The record does not report a formal sample-size justification for this study or numerical planning results. Any such justification is not reported in the registry record. The enrollment entry should not be interpreted as a calculated sample-size target unless the record explicitly says so.
The registry also does not report an interim-analysis plan, stopping boundaries, or a multiplicity procedure. The number of analyses listed is zero, so no recorded analysis methods can be used to evaluate whether repeated measurements, multiple dose cohorts, or multiple outcomes were handled in a particular way. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies seven outcome measures, including the primary Cmax measure and secondary outcomes for recommending a phase 2 dose and assessing the percentage of participants with anti-IMC-CS4 antibodies. It records no analysis entries. The endpoint list therefore describes the outcomes of interest but does not show which statistical tests, estimates, or models were used for them.
Multiplicity can arise when several outcomes, dose cohorts, time points, or comparisons are examined. As a general statistical matter, conducting multiple tests can increase the chance of at least one apparently unusual result under a null hypothesis. A prespecified approach may address this, for example by defining a primary analysis or adjusting inference across tests. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a formal analysis strategy for the several sampling times and dose schedules. It is not possible to determine from the record whether or how multiplicity was considered.
The primary pharmacokinetic population is described as participants who were enrolled, received at least one dose, and had evaluable Cmax data. The record does not give the number with evaluable data, the number contributing at each sampling time, or reasons for missing measurements. It does not report imputation, rules for excluding incomplete records, or sensitivity analyses addressing missing data. These methods are not reported in the registry record.
For safety, the registry presents cohort-level counts with cohort-specific numbers at risk. The record does not explain how participants with incomplete follow-up were handled in those summaries or whether exposure duration was incorporated. Missing-data methods, analysis populations for the secondary outcomes, and details of any interim analyses are not reported in the registry record. Consequently, the listed outcome count and population definition alone are not enough to reconstruct the analyses.
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 |
|---|---|---|---|
| Cohort 1 (2.5 mg/kg QW) | 0 | 6 | 0.0% |
| Cohort 2 (0.3 mg/kg QW) | 1 | 4 | 25.0% |
| Cohort 3 (0.6 mg/kg QW) | 2 | 3 | 66.7% |
| Cohort 4 (1.25 mg/kg Q2W) | 2 | 6 | 33.3% |
| Cohort 4 Expanded (1.25 mg/kg Q2W) | 2 | 5 | 40.0% |
| Cohort 5 (1.25 mg/kg QW) | 3 | 5 | 60.0% |
| Cohort 6a (100 mg QW) | 1 | 3 | 33.3% |
| Cohort 6a Expanded (100 mg QW) | 4 | 11 | 36.4% |
| Cohort 7a (150 mg QW) | 3 | 9 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 (2.5 mg/kg QW) | 0 of 6 |
| Cohort 2 (0.3 mg/kg QW) | 2 of 4 |
| Cohort 3 (0.6 mg/kg QW) | 1 of 3 |
| Cohort 4 (1.25 mg/kg Q2W) | 1 of 6 |
| Cohort 4 Expanded (1.25 mg/kg Q2W) | 1 of 5 |
| Cohort 5 (1.25 mg/kg QW) | 1 of 5 |
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 |
|---|---|
| Cohort 1 (2.5 mg/kg QW) | 6 of 6 |
| Cohort 2 (0.3 mg/kg QW) | 4 of 4 |
| Cohort 3 (0.6 mg/kg QW) | 3 of 3 |
| Cohort 4 (1.25 mg/kg Q2W) | 6 of 6 |
| Cohort 4 Expanded (1.25 mg/kg Q2W) | 4 of 5 |
| Cohort 5 (1.25 mg/kg QW) | 3 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 (2.5 mg/kg QW) | Cohort 2 (0.3 mg/kg QW) | Cohort 3 (0.6 mg/kg QW) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 5 (1.25 mg/kg QW) |
|---|---|---|---|---|---|---|---|
| Left ventricular dysfunction | Cardiac disorders | 0 of 6 | 0 of 4 | 0 of 3 | 1 of 6 | 0 of 5 | 0 of 5 |
| Tachycardia | Cardiac disorders | 0 of 6 | 0 of 4 | 1 of 3 | 0 of 6 | 0 of 5 | 0 of 5 |
| Ascites | Gastrointestinal disorders | 0 of 6 | 1 of 4 | 0 of 3 | 0 of 6 | 0 of 5 | 0 of 5 |
| Pancreatitis | Gastrointestinal disorders | 0 of 6 | 0 of 4 | 0 of 3 | 0 of 6 | 0 of 5 | 1 of 5 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 6 | 0 of 4 | 0 of 3 | 0 of 6 | 1 of 5 | 0 of 5 |
| Fatigue | General disorders | 0 of 6 | 0 of 4 | 0 of 3 | 0 of 6 | 0 of 5 | 1 of 5 |
| Sudden death | General disorders | 0 of 6 | 0 of 4 | 1 of 3 | 0 of 6 | 0 of 5 | 0 of 5 |
| Localised infection | Infections and infestations | 0 of 6 | 0 of 4 | 0 of 3 | 1 of 6 | 0 of 5 | 0 of 5 |
| Toxicity to various agents | Injury, poisoning and procedural complications | 0 of 6 | 1 of 4 | 0 of 3 | 0 of 6 | 0 of 5 | 0 of 5 |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | 0 of 6 | 0 of 4 | 0 of 3 | 0 of 6 | 0 of 5 | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 (2.5 mg/kg QW) | Cohort 2 (0.3 mg/kg QW) | Cohort 3 (0.6 mg/kg QW) | Cohort 4 (1.25 mg/kg Q2W) | Cohort 4 Expanded (1.25 mg/kg Q2W) | Cohort 5 (1.25 mg/kg QW) |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 2 of 6 | 2 of 4 | 3 of 3 | 5 of 6 | 2 of 5 | 1 of 5 |
| Hypoalbuminaemia | Metabolism and nutrition disorders | 1 of 6 | 2 of 4 | 3 of 3 | 2 of 6 | 3 of 5 | 1 of 5 |
| Nausea | Gastrointestinal disorders | 2 of 6 | 1 of 4 | 1 of 3 | 2 of 6 | 2 of 5 | 2 of 5 |
| Aspartate aminotransferase increased | Investigations | 4 of 6 | 0 of 4 | 2 of 3 | 0 of 6 | 3 of 5 | 1 of 5 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 6 | 3 of 4 | 1 of 3 | 1 of 6 | 1 of 5 | 2 of 5 |
| Anaemia | Blood and lymphatic system disorders | 1 of 6 | 0 of 4 | 2 of 3 | 1 of 6 | 3 of 5 | 1 of 5 |
| Blood creatine phosphokinase increased | Investigations | 4 of 6 | 0 of 4 | 1 of 3 | 0 of 6 | 2 of 5 | 0 of 5 |
| Constipation | Gastrointestinal disorders | 1 of 6 | 0 of 4 | 0 of 3 | 1 of 6 | 2 of 5 | 2 of 5 |
| Diarrhoea | Gastrointestinal disorders | 1 of 6 | 1 of 4 | 1 of 3 | 0 of 6 | 1 of 5 | 2 of 5 |
| Hypertension | Vascular disorders | 2 of 6 | 0 of 4 | 1 of 3 | 1 of 6 | 1 of 5 | 1 of 5 |
Serious events with the highest arm-level rate: tachycardia (33.3%), sudden death (33.3%), chronic kidney disease (33.3%), pleural effusion (33.3%), pneumothorax (33.3%).
The registry reports serious-adverse-event and other-adverse-event affected counts separately by cohort, alongside the number at risk for each category. In the order listed, the serious-event figures are 0 of 6 in Cohort 1 (2.5 mg/kg QW), 1 of 4 in Cohort 2 (0.3 mg/kg QW), 2 of 3 in Cohort 3 (0.6 mg/kg QW), 2 of 6 in Cohort 4 (1.25 mg/kg Q2W), 2 of 5 in Cohort 4 Expanded (1.25 mg/kg Q2W), 3 of 5 in Cohort 5 (1.25 mg/kg QW), 1 of 3 in Cohort 6a (100 mg QW), 4 of 11 in Cohort 6a Expanded (100 mg QW), and 3 of 9 in Cohort 7a (150 mg QW). The other-adverse-event figures are 6 of 6, 4 of 4, 3 of 3, 6 of 6, 4 of 5, 3 of 5, 3 of 3, 11 of 11, and 9 of 9, respectively.
Deaths are also listed by cohort: 0, 2, 1, 1, 1, 1, 1, 2, and 0, respectively. The registry lists Tachycardia, Sudden death, Chronic kidney disease, Pleural effusion, Pneumothorax, and Pulmonary haemorrhage as serious-event terms, each at 33.3%. The denominator and calculation underlying these term percentages are not reported in the registry record. These descriptive figures do not establish that IMC-CS4 caused an event or death; event attribution and further timing details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
This study addresses early-phase characterization of IMC-CS4 in participants with advanced solid tumors. The registry identifies Cmax as the primary endpoint and describes sampling times, dosing cohorts, and a population requiring at least one dose and evaluable pharmacokinetic data. These details clarify what the study set out to measure. They do not reveal the measured Cmax values: numerical primary endpoint results are not reported in the registry record.
The record also reports cohort-level adverse-event and death counts. Those counts describe what was recorded for the listed groups, but they are not a controlled comparison and do not establish causation. In particular, the non-randomized sequential design means that a difference between cohorts could reflect factors other than the dosing schedule. No comparator arm is listed, and the cohort summaries should not be read as proof that one regimen is safer or less safe than another.
The endpoint is pharmacokinetic rather than a direct measure of tumor response or survival. Although the study's stated purpose included establishing a safety profile, the recorded information does not provide a complete account of event timing, attribution, or follow-up. Nor does it report numerical results for the secondary outcomes of recommended phase 2 dose and anti-IMC-CS4 antibody assessment.
Accordingly, the registry record supports describing the study design, dosing schedules, endpoint definition, and reported safety counts. It does not support a quantitative conclusion about the size or precision of pharmacokinetic effects, a causal dose comparison, or a claim about clinical benefit. Statistical interpretation beyond those descriptive details would require results and methods that are not reported in the registry record.
13. Why This Trial Matters Statistically
Phase 1 studies often need to characterize drug exposure and safety across dose schedules before later studies can address other questions. This record makes the distinction between those aims and a randomized efficacy comparison especially important. IMC-CS4 was studied in sequential, non-randomized cohorts, with Cmax named as the primary pharmacokinetic endpoint and safety outcomes reported by cohort. The design is useful to describe what was measured and in whom, but it does not create a controlled estimate of the effect of one dose schedule versus another.
The endpoint definition also illustrates why a statistical result requires more than naming a measure. The record specifies the geometric mean and geometric coefficient of variation, sampling times, and the population intended for the primary measure. Without numerical estimates, variability, and analysis details, readers cannot evaluate the magnitude or precision of the pharmacokinetic findings. This distinction between an endpoint description and a result is central to responsible interpretation of registry data.
The safety summaries are similarly informative as descriptive counts but limited for comparative inference. Cohort sizes differ, allocation was not randomized, and the record does not provide event attribution or exposure-adjusted analyses. A count alone does not establish a risk difference, and no new comparisons should be calculated from these summaries without a prespecified and appropriate analysis.
Finally, the record's lack of listed analysis entries highlights the value of transparent reporting of analysis populations, missing-data handling, uncertainty intervals, and multiplicity decisions. Those details help readers judge how robust a result is and whether the reported estimate answers the clinical question. In their absence, the most defensible reading is a careful account of the design and reported observations, with unreported results and methods left unresolved.
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 primary limitation for statistical interpretation is that the registry record does not report numerical Cmax results, despite identifying Cmax as the primary outcome and specifying its summary measures. No estimate, variability value, or confidence interval is available in the record to assess the magnitude or precision of the pharmacokinetic findings. The record also lists no analysis entries, so the methods used to produce any study results cannot be evaluated from those entries.
The study was non-randomized and sequential, with no control arm. Consequently, cohort comparisons are not like-for-like comparisons and may be affected by differences other than dose. The registry does not report the detailed rules for cohort progression, dose escalation, or selection of a recommended phase 2 dose. It also does not report a statistical plan, a formal sample-size justification, or an interim-analysis plan.
The Cmax population is defined by receipt of at least one dose and evaluable data, but the number of evaluable participants and the handling of missing measurements are not reported in the registry record. The record does not give participant counts for each sampling time, explain missingness, or describe imputation or sensitivity analyses. Thus, the representativeness of the available pharmacokinetic measurements cannot be assessed from the registry entry.
Safety information is limited to cohort-level affected counts, death counts, and a list of serious-event terms with percentages. Event timing, duration, severity details, attribution to treatment, exposure-adjusted rates, and the basis for the term percentages are not reported in the registry record. These limitations mean the listed counts should remain descriptive and should not be treated as causal comparisons or as a complete assessment of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of IMC-CS4 in Subjects With Advanced Solid Tumors — NCT01346358.
- Registry record last updated 2024-09-19; status last verified 2024-05.
- Results first posted 2024-09-19.
- 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
NCT01346358 is a completed phase 1 study of IMC-CS4 in participants with advanced solid tumors refractory to standard therapy or for which no standard therapy was available. The registry lists 52 enrolled participants. Allocation was non-randomized, masking was none, and the model was sequential. The listed study dates are 2011-06-15 for start and 2018-05-31 for primary completion.
The study used weight-based and non-weight-based intravenous dosing cohorts. Its primary outcome was Cmax, summarized as a geometric mean with geometric coefficient of variation at specified sampling times. The primary population was participants who received at least one dose and had evaluable Cmax data. Secondary outcomes included recommending a phase 2 dose and assessing anti-IMC-CS4 antibodies. The record lists seven outcome measures and no analysis entries. Numerical Cmax findings and further statistical methods are not reported in the registry record.