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 Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies (NCT03881488), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs), Treatment-emergent Adverse Events (TEAEs), and/or Changes in Clinical Laboratory Abnormalities.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03881488 |
| Phase | Phase 1 |
| Condition | Locally Advanced Solid Tumor, Metastatic Cancer, Non-small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 100 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Compass Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastatic or locally advanced malignancies who had inadequate responses to PD-1/PD-L1 checkpoint inhibitors. The listed conditions include locally advanced solid tumors, metastatic cancer, non-small cell lung cancer, small cell lung cancer, mesothelioma, melanoma, and head and neck cancer. The record does not give further eligibility details or participant characteristics.
Intervention
CTX-471, given as monotherapy or with pembrolizumab. The study included dose escalation and dose expansion. The expansion doses described were 0.3 mg/kg and 0.6 mg/kg; the combination expansion used pembrolizumab at 400 mg and included tumor-type subgroups.
Comparator
There was no randomized control group. The study was non-randomized, open-label, and sequential. Its treatment arms and dose groups therefore do not form a like-for-like controlled comparison. Differences between groups cannot be attributed to treatment alone from these data.
Primary question
The primary endpoint counts participants with dose-limiting toxicities, treatment-emergent adverse events, and/or changes in clinical laboratory abnormalities. It is a safety and tolerability question: what adverse events and laboratory changes were recorded after CTX-471 was started? The registry record does not report the primary endpoint results.
The study addressed treatment in a population whose malignancies had progressed while receiving an approved PD-1 or PD-L1 inhibitor, according to the study description. It evaluated CTX-471 by itself and in combination with pembrolizumab. Because the study was first-in-human and Phase 1, dose escalation and safety monitoring were central features of its design. The record also lists pharmacokinetic outcomes, anti-drug antibodies, overall response rate, duration of response, progression-free survival, and overall survival as secondary outcomes. Their results are not reported in the registry record.
3. Trial Design
This was a Phase 1, open-label, non-randomized, sequential study of CTX-471 as monotherapy or in combination with pembrolizumab. The listed enrollment was 100. The study began on 2019-05-17, had a primary completion date of 2025-05-21, and is recorded as terminated. These registry entries describe the study record; they do not explain why the study was terminated.
The study had two treatment arms, each with a dose-escalation part and a dose-expansion part. In monotherapy dose escalation, CTX-471 doses increased by enrollment cohort. The expansion part included 0.3 mg/kg and 0.6 mg/kg groups. In the combination arm, CTX-471 dose escalation was also cohort-dependent, with pembrolizumab given alongside it. The combination expansion included CTX-471 at 0.3 mg/kg and 0.6 mg/kg, with pembrolizumab at 400 mg, and tumor-type subgroups for non-small cell lung cancer, small cell lung cancer, and melanoma.
The registry description says data from dose escalation and dose expansion were combined by dose level for reporting in each arm. This means that a dose-level summary may include participants from both parts; the registry does not provide a separate breakdown by study part in the registry record for this analysis. Dose groups are not randomized treatment comparisons. They may also differ in when and how participants entered the sequential study, so apparent differences should be treated descriptively.
The record does not report allocation procedures beyond non-randomized assignment, masking beyond none, or detailed statistical analysis methods. It also does not report a protocol rationale for the selected doses or a sample-size justification.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | CTX-471 Monotherapy 0.1 mg/kg | CTX-471 Monotherapy 0.3 mg/kg | CTX-471 Monotherapy 0.6 mg/kg | CTX-471 Monotherapy 1.2 mg/kg | CTX-471 Combination 0.1 mg/kg | CTX-471 Combination 0.3 mg/kg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 33 | 36 | 7 | 3 | 9 |
| COMPLETED | 0 | 5 | 3 | 2 | 0 | 0 |
| NOT COMPLETED | 3 | 28 | 33 | 5 | 3 | 9 |
Reasons for not completing this period:
| Reason | CTX-471 Monotherapy 0.1 mg/kg | CTX-471 Monotherapy 0.3 mg/kg | CTX-471 Monotherapy 0.6 mg/kg | CTX-471 Monotherapy 1.2 mg/kg | CTX-471 Combination 0.1 mg/kg | CTX-471 Combination 0.3 mg/kg |
|---|---|---|---|---|---|---|
| Death | 3 | 22 | 30 | 5 | 2 | 5 |
| Lost to Follow-up | 0 | 2 | 1 | 0 | 0 | 0 |
| Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 3 | 0 | 0 | 0 | 2 |
| Study termination by sponsor | 0 | 1 | 0 | 0 | 1 | 2 |
| Clinical deterioration | 0 | 0 | 1 | 0 | 0 | 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.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | CTX-471 Monotherapy 0.1 mg/kg | CTX-471 Monotherapy 0.3 mg/kg | CTX-471 Monotherapy 0.6 mg/kg | CTX-471 Monotherapy 1.2 mg/kg | CTX-471 Combination 0.1 mg/kg | CTX-471 Combination 0.3 mg/kg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 33 | 36 | 7 | 3 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 12 | 12 | 4 | 1 | 6 |
| Age, Categorical: >=65 years | Participants | 2 | 21 | 24 | 3 | 2 | 3 |
| Sex: Female, Male: Female | Participants | 1 | 12 | 14 | 1 | 2 | 5 |
| Sex: Female, Male: Male | Participants | 2 | 21 | 22 | 6 | 1 | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 2 | 1 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 31 | 34 | 6 | 3 | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 3 | 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 | 1 | 2 | 3 | 2 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 30 | 30 | 5 | 3 | 9 |
| 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 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | 33 | 36 | 7 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs), Treatment-emergent Adverse Events (TEAEs), and/or Changes in Clinical Laboratory Abnormalities, measured over From first CTX-471 dose to 4 weeks after first dose for DLTs in monotherapy arms, to 6 weeks after first dose for DLTs in combination arms, to 60 days after last dose for TEAEs and clinical laboratory abnormalities in both monotherapy and combination arms.
| 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 dose-limiting toxicities, treatment-emergent adverse events, and/or changes in clinical laboratory abnormalities. It is expressed as a participant count, not as a continuous measurement. The endpoint combines several safety concepts: protocol-defined hematological and nonhematological dose-limiting toxicities; adverse events that started or worsened in severity on or after the first CTX-471 dose; and clinical laboratory changes treated as adverse events related to laboratory results.
The endpoint is used in early-phase drug research to characterize tolerability and identify safety events for further evaluation. Dose-limiting toxicities are especially relevant during dose escalation because they help describe whether a dose level raises safety concerns under the protocol’s definitions. Treatment-emergent adverse events and laboratory abnormalities capture a broader range of events occurring after treatment begins. These categories are not interchangeable: an event may be treatment-emergent without meeting the protocol definition of a dose-limiting toxicity.
The registry specifies different observation windows. Dose-limiting toxicities were assessed from the first CTX-471 dose through 4 weeks after the first dose in monotherapy arms and through 6 weeks after the first dose in combination arms. Treatment-emergent adverse events and clinical laboratory abnormalities were followed through 60 days after the last dose in both arms. These windows matter when interpreting counts because the time available to record events differs by event category and arm. The primary endpoint results themselves are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a safety-focused Phase 1 investigation, but it does not report the primary endpoint results. Consequently, the record does not establish how many participants experienced the combined primary endpoint, how many had dose-limiting toxicities, or how the observed safety profile varied across the study parts. The posted adverse-event counts offer some descriptive information by dose group, but they do not replace the missing primary outcome results.
The safety record lists participants at risk and participants affected by serious adverse events for each dose group. For monotherapy, the listed serious-event counts are 1 of 3 at 0.1 mg/kg, 11 of 33 at 0.3 mg/kg, 17 of 36 at 0.6 mg/kg, and 3 of 7 at 1.2 mg/kg. For combination treatment, they are 2 of 3 at 0.1 mg/kg, 2 of 9 at 0.3 mg/kg, and 4 of 9 at 0.6 mg/kg. These are descriptive counts, not estimates from a randomized comparison. The group sizes differ, and the record does not provide adjustment for differences among participants or exposure time.
The listed death counts are 3, 22, 30, and 5 in the monotherapy groups, and 2, 5, and 5 in the combination groups, respectively. The registry record does not establish from these counts whether deaths were caused by treatment, the underlying malignancy, or another factor. Nor does it provide enough detail to interpret timing, follow-up completeness, or cause of death. These counts must not be treated as evidence of a treatment effect.
The serious-event terms listed include hypoxia, urinary tract infection, bile duct obstruction, acute kidney injury, tubulointerstitial nephritis, and headache. The registry lists 33.3% for each of the first five terms and 14.3% for headache. The denominator and the precise basis for these percentages are not reported in the registry record, so they should not be interpreted as incidence estimates for all enrolled participants or as comparisons between arms.
There are no reported statistical analyses in the registry record. No confidence intervals, hypothesis tests, or adjusted treatment comparisons are available in the registry record for this analysis. The absence of such results is important: counts alone do not show the precision of a treatment effect, and the design does not support a controlled causal contrast.
9. Statistical Methods Explained
The statistical information should be read in light of the study’s purpose and design. This was a first-in-human Phase 1 study with dose escalation and dose expansion, not a randomized efficacy trial. The main statistical role of early-phase summaries is to describe observed safety and tolerability across dose groups and to support decisions about continued investigation. Such summaries are not, by themselves, proof that a treatment caused an event or changed a clinical outcome.
What does a participant count describe?
A count reports how many participants met a stated event definition. Counts are most informative when the population being counted, the event definition, and the observation period are clear. The primary endpoint combines dose-limiting toxicities, treatment-emergent adverse events, and clinical laboratory abnormalities. Those are distinct concepts, and a combined endpoint can obscure which component accounts for a result unless component-specific counts are also reported. The primary endpoint count and its component results are not reported in the registry record.
For the adverse-event summaries, each dose group has a number of participants at risk and a number affected by serious adverse events. The denominator is essential: an affected count from a small group has different precision from the same count in a larger group. Even when denominators are given, a proportion is descriptive unless the study design and analysis support a comparison. These groups were not randomized, so their observed counts cannot be read as an unbiased comparison of CTX-471 doses or of monotherapy versus combination treatment.
Why does non-randomized allocation matter?
Randomization is a general method for making treatment groups comparable, on average, with respect to known and unknown participant characteristics. This study was non-randomized and sequential. Assignment to a dose group may therefore be related to study stage, cohort, tumor subgroup, or other factors. The registry does not report the allocation details needed to assess those relationships. A difference between groups could reflect participant composition, follow-up, treatment exposure, or chance, in addition to any treatment-related difference. No like-for-like control comparison is available.
Open-label means masking was absent. In general, knowledge of the assigned treatment can affect reporting or assessment of outcomes that involve judgment. The degree to which that could affect these safety summaries is not assessed in the registry record. Laboratory values may be more objectively measured than some reported symptoms, but interpretation and classification still depend on the study’s procedures and definitions, which are not fully described in the available record.
What do uncertainty estimates add?
In general, a confidence interval describes a range of effect estimates compatible with the data under a statistical model and its assumptions. It communicates precision as well as the central estimate. A p-value, in general, describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the analysis assumptions. Neither quantity alone establishes clinical importance or causation. No confidence intervals or hypothesis-test results are reported in the registry record for the primary endpoint, and the record lists no analyses.
For simple participant counts, uncertainty is affected by the number of participants and the event frequency. Small groups commonly produce imprecise estimates; a count should not be treated as a precise rate simply because it is displayed as a whole number. Follow-up time also matters when participants have differing time under observation. The registry record does not provide person-time summaries or enough follow-up detail to calculate event rates. No new rates or uncertainty estimates should be inferred from the listed counts.
How should planning illustrations be read?
The study’s sample-size assumptions describe a planning illustration based on an observed effect, not the trial’s original design. The assumptions listed are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. For time-to-event outcomes, the stated illustration concerns the total number of events; other illustrations concern participants per arm. These are planning scenarios, not observed power and not evidence that the study was designed to achieve those targets.
In general, sample-size planning asks how much information a future study would need to detect a chosen effect under stated assumptions. The result depends on the chosen effect, variability or event frequency, error rate, allocation, and analysis model. A planning illustration does not tell readers how likely the observed result was to be true, nor can it compensate for the absence of a randomized comparison. The actual numerical planning outputs and the observed effect underlying them are not reported in the registry record available for this analysis.
The record does not report interim analysis procedures, a prespecified statistical analysis plan, missing-data methods, or a justification for the enrollment target. Those details should not be inferred from the study’s Phase 1 label or its dose-escalation structure. The statistical conclusions are therefore limited to describing the design and the posted counts, while treating all treatment comparisons as non-causal and uncertain.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes: maximum serum concentration of CTX-471, area under the serum concentrations of CTX-471 versus time curve, half-life of serum concentration, development of anti-drug antibodies, overall response rate, duration of response, progression-free survival, and overall survival. The record also describes several dose groups and tumor subgroups. Considering many outcomes or subgroups can increase the chance of finding an apparently notable result by chance when formal statistical tests are conducted. In general, multiplicity is addressed by prespecifying a primary question and, where appropriate, adjusting analyses or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy.
The registry record does not report the analysis populations used for the primary or secondary outcomes, including whether all enrolled participants or only treated participants were included. It does not report how missing outcome data, incomplete follow-up, or participants who discontinued treatment were handled. These omissions matter because the number observed for an outcome may depend on who was included and how long they were followed.
The primary endpoint includes observation windows that differ by arm for dose-limiting toxicities and a separate window for treatment-emergent adverse events and laboratory abnormalities. The record does not give participant-level follow-up completeness or explain how events outside those windows were treated in analyses. No interim analysis plan, missing-data method, or detailed statistical analysis plan is reported in the registry record. The posted results therefore cannot be evaluated for these features from the available information.
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 |
|---|---|---|---|
| CTX-471 Monotherapy 0.1 mg/kg | 1 | 3 | 33.3% |
| CTX-471 Monotherapy 0.3 mg/kg | 11 | 33 | 33.3% |
| CTX-471 Monotherapy 0.6 mg/kg | 17 | 36 | 47.2% |
| CTX-471 Monotherapy 1.2 mg/kg | 3 | 7 | 42.9% |
| CTX-471 Combination 0.1 mg/kg | 2 | 3 | 66.7% |
| CTX-471 Combination 0.3 mg/kg | 2 | 9 | 22.2% |
| CTX-471 Combination 0.6 mg/kg | 4 | 9 | 44.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| CTX-471 Monotherapy 0.1 mg/kg | 3 of 3 |
| CTX-471 Monotherapy 0.3 mg/kg | 22 of 33 |
| CTX-471 Monotherapy 0.6 mg/kg | 30 of 36 |
| CTX-471 Monotherapy 1.2 mg/kg | 5 of 7 |
| CTX-471 Combination 0.1 mg/kg | 2 of 3 |
| CTX-471 Combination 0.3 mg/kg | 5 of 9 |
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 |
|---|---|
| CTX-471 Monotherapy 0.1 mg/kg | 2 of 3 |
| CTX-471 Monotherapy 0.3 mg/kg | 33 of 33 |
| CTX-471 Monotherapy 0.6 mg/kg | 36 of 36 |
| CTX-471 Monotherapy 1.2 mg/kg | 7 of 7 |
| CTX-471 Combination 0.1 mg/kg | 3 of 3 |
| CTX-471 Combination 0.3 mg/kg | 8 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | CTX-471 Monotherapy 0.1 mg/kg | CTX-471 Monotherapy 0.3 mg/kg | CTX-471 Monotherapy 0.6 mg/kg | CTX-471 Monotherapy 1.2 mg/kg | CTX-471 Combination 0.1 mg/kg | CTX-471 Combination 0.3 mg/kg |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 3 | 2 of 33 | 2 of 36 | 0 of 7 | 0 of 3 | 1 of 9 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 3 | 1 of 33 | 1 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 1 of 33 | 2 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
| Cytokine release syndrome | Immune system disorders | 0 of 3 | 0 of 33 | 2 of 36 | 0 of 7 | 0 of 3 | 1 of 9 |
| Sepsis | Infections and infestations | 0 of 3 | 0 of 33 | 2 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
| Urinary tract infection | Infections and infestations | 0 of 3 | 1 of 33 | 0 of 36 | 0 of 7 | 1 of 3 | 0 of 9 |
| Abdominal pain | Gastrointestinal disorders | 0 of 3 | 2 of 33 | 0 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 3 | 2 of 33 | 0 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
| Platelet count decreased | Investigations | 0 of 3 | 0 of 33 | 1 of 36 | 1 of 7 | 0 of 3 | 0 of 9 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 0 of 33 | 1 of 36 | 0 of 7 | 0 of 3 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | CTX-471 Monotherapy 0.1 mg/kg | CTX-471 Monotherapy 0.3 mg/kg | CTX-471 Monotherapy 0.6 mg/kg | CTX-471 Monotherapy 1.2 mg/kg | CTX-471 Combination 0.1 mg/kg | CTX-471 Combination 0.3 mg/kg |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 0 of 3 | 13 of 33 | 12 of 36 | 2 of 7 | 3 of 3 | 6 of 9 |
| Anaemia | Blood and lymphatic system disorders | 1 of 3 | 9 of 33 | 12 of 36 | 3 of 7 | 1 of 3 | 2 of 9 |
| Nausea | Gastrointestinal disorders | 1 of 3 | 9 of 33 | 10 of 36 | 2 of 7 | 2 of 3 | 2 of 9 |
| Constipation | Gastrointestinal disorders | 0 of 3 | 11 of 33 | 8 of 36 | 4 of 7 | 0 of 3 | 2 of 9 |
| Vomiting | Gastrointestinal disorders | 1 of 3 | 9 of 33 | 9 of 36 | 0 of 7 | 2 of 3 | 1 of 9 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 3 | 6 of 33 | 6 of 36 | 0 of 7 | 2 of 3 | 5 of 9 |
| Weight decreased | Investigations | 0 of 3 | 10 of 33 | 4 of 36 | 0 of 7 | 1 of 3 | 3 of 9 |
| Oedema peripheral | General disorders | 1 of 3 | 2 of 33 | 10 of 36 | 0 of 7 | 1 of 3 | 3 of 9 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 3 | 7 of 33 | 5 of 36 | 1 of 7 | 2 of 3 | 1 of 9 |
| Pyrexia | General disorders | 1 of 3 | 4 of 33 | 5 of 36 | 2 of 7 | 2 of 3 | 2 of 9 |
Serious events with the highest arm-level rate: hypoxia (33.3%), urinary tract infection (33.3%), bile duct obstruction (33.3%), acute kidney injury (33.3%), tubulointerstitial nephritis (33.3%).
The serious adverse-event summaries are counts by dose group. For each group, the record gives the number at risk and the number affected; these figures describe what was recorded, not the probability that CTX-471 caused an event. The monotherapy groups list 1 of 3, 11 of 33, 17 of 36, and 3 of 7 participants affected at 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg, respectively. The combination groups list 2 of 3, 2 of 9, and 4 of 9 participants affected at 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg, respectively.
Because this was a non-randomized sequential study, these groups are not suitable for direct causal comparisons. Group sizes differ, and the record does not report exposure-adjusted event rates or sufficient information about participant characteristics and follow-up. The death counts are also listed, but the registry record does not specify their causes or establish treatment attribution. They should not be read as treatment-caused deaths.
The registry lists serious-event terms with percentages, but does not report the denominator or percentage calculation basis in the record details. Those percentages should therefore be treated as registry-listed descriptors rather than comparable group-level risks.
12. What the Result Does, and Does Not, Mean
The posted information establishes that CTX-471 was studied as monotherapy and with pembrolizumab in a Phase 1, open-label, non-randomized, sequential design among patients with advanced malignancies after inadequate response to PD-1/PD-L1 inhibitors. It also establishes that the registry lists serious adverse-event counts across dose groups and records the study as terminated. The dose-level counts are descriptive and should be interpreted alongside their group sizes and the limits of the study design.
The registry record does not report the primary endpoint results, so it does not show the overall number of participants with dose-limiting toxicities, treatment-emergent adverse events, and/or laboratory abnormalities under the primary endpoint definition. It also does not report results for the listed secondary outcomes, including pharmacokinetic measures, anti-drug antibodies, response, progression-free survival, or overall survival. Without these results, the record cannot support conclusions about the magnitude or precision of those outcomes.
The data do not establish that CTX-471 caused the listed serious adverse events or deaths. They also do not establish whether monotherapy or combination treatment is safer or more effective, whether one dose is preferable, or whether the treatment changes tumor response or survival. The non-randomized design lacks a like-for-like control group, and the group counts may reflect differences beyond treatment.
In general, early-phase studies can characterize observed safety and guide further investigation, but their findings are not equivalent to confirmatory evidence from a controlled comparison. The interpretation is further constrained by the absent primary outcome results, absent analysis details, and unreported information about missing data and analysis populations. The findings should be understood as a limited registry description, not a treatment recommendation or a definitive assessment of benefit and harm.
13. Why This Trial Matters Statistically
This trial is statistically notable because its design combines sequential dose escalation with dose expansion in a first-in-human setting. Such designs prioritize learning about tolerability across dose levels rather than estimating a treatment effect against a randomized control. The distinction matters: descriptive safety counts can inform what was observed in participants, but they do not isolate the effect of treatment from participant characteristics, disease course, or differences in exposure and follow-up.
The study also combined data from dose escalation and dose expansion by dose level for reporting, according to the registry description. This makes the dose-group summaries a mixture of participants enrolled in different study parts. Readers need to know that structure before interpreting the counts as if they represented a single uniformly enrolled cohort. The record does not provide enough detail to separate those contributions in the registry entries.
Several outcomes were planned, spanning safety, pharmacokinetics, immunogenicity, response, and survival. In general, a broad outcome set can address different aspects of an investigational treatment, while also raising questions about multiplicity, missingness, analysis populations, and prespecification. Those statistical details are not reported in the registry record. The distinction between listed outcomes and posted results is especially important: an outcome being named does not mean its result is available.
The record illustrates why study design and reporting completeness are part of statistical interpretation. Non-randomized group counts do not provide a controlled estimate, and missing primary results prevent assessment of the stated main safety endpoint. The reported information can be read descriptively, but it does not support a definitive efficacy or comparative safety conclusion.
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.
Important study details are not reported in the registry record. These include the eligibility criteria in full, participant baseline characteristics, the allocation process beyond its non-randomized classification, and the rationale for the enrollment target. Without baseline information, the comparability of dose groups cannot be assessed. Without a sample-size justification, the intended precision or decision criteria cannot be evaluated.
The primary endpoint results are not reported, despite the endpoint being defined with different observation windows for dose-limiting toxicities and other safety events. The registry record also does not report the component counts, event timing, exposure duration, or completeness of follow-up needed to examine those outcomes in depth. The listed deaths are not accompanied by causes or treatment attribution. The serious-event terms and their percentages lack a reported denominator basis in the record details available for this analysis.
The record lists secondary outcomes but does not report their results or analysis methods. It does not report which analysis populations were used, how missing data or treatment discontinuation were handled, whether interim analyses occurred, or how multiplicity was addressed. Details of event adjudication and the statistical analysis plan are also not reported in the registry record.
Finally, the study was open-label, non-randomized, and sequential, with no like-for-like control group. Dose-level differences could reflect factors other than treatment. These constraints mean that the posted safety counts should be treated as descriptive, and the registry information cannot establish comparative effects or causal conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies — NCT03881488.
- Registry record last updated 2026-10-09; status last verified 2025-06.
- Results first posted 2026-10-09.
- 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
The registry record describes a Phase 1, open-label, non-randomized, sequential study of CTX-471 as monotherapy or in combination with pembrolizumab in patients with metastatic or locally advanced malignancies after inadequate response to PD-1/PD-L1 checkpoint inhibitors. It lists enrollment of 100, a start date of 2019-05-17, primary completion on 2025-05-21, and terminated status.
Both treatment arms included dose escalation and dose expansion. The primary endpoint was a count of participants with dose-limiting toxicities, treatment-emergent adverse events, and/or clinical laboratory abnormalities. Serious adverse-event and death counts are listed by dose group. The primary endpoint results and the listed secondary outcome results are not reported in the registry record. No statistical analyses are listed, and the record does not report a randomized comparison, analysis populations, missing-data methods, or a multiplicity strategy.