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 MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study. (NCT03611556), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03611556 |
| Phase | Phase 1, Phase 2 |
| Condition | Carcinoma, Metastatic Pancreatic Adenocarcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 213 |
| Arms in the primary outcome | n/a |
| Lead sponsor | MedImmune LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants had metastatic pancreatic ductal adenocarcinoma. The registry describes first-line metastatic disease in several gemcitabine plus nab-paclitaxel groups and second-line metastatic disease in the mFOLFOX dose-escalation groups. The total reported enrollment was 213.
Intervention
The study evaluated oleclumab, also called MEDI9447, with chemotherapy, with or without durvalumab. Dose-escalation regimens included oleclumab 1500 mg or 3000 mg with durvalumab and chemotherapy. Dose-expansion regimens included chemotherapy alone, oleclumab 3000 mg with chemotherapy, or oleclumab 3000 mg with durvalumab and chemotherapy.
Comparator
The listed dose-expansion groups include gemcitabine plus nab-paclitaxel without oleclumab or durvalumab, alongside groups adding oleclumab, with or without durvalumab. The registry identifies the study as randomized, but the allocation method, allocation proportions, and which specific groups were formally compared are not reported in the registry record.
Primary question
The primary outcome asks how many participants in the dose-escalation phase experienced treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs). It is a safety-focused count, not a direct measure of antitumor activity. The registry also lists response and disease-control outcomes in dose escalation and survival outcomes in dose expansion, but their results are not reported in the registry record.
In statistical terms, the study combines dose escalation and dose expansion with different regimens and disease-line settings. The safety count therefore needs to be read in the context of each group’s treatment and phase, rather than as a single comparison across all participants.
3. Trial Design
The registry describes a randomized, non-masked, parallel-group Phase 1b/2 study. It lists an enrollment of 213 and a completed status. The recorded study start was 2018-06-21, and primary completion was 2022-07-22. The sponsor is MedImmune LLC.
The dose-escalation regimens paired oleclumab at 1500 mg or 3000 mg with durvalumab and chemotherapy. The first-line metastatic disease groups received gemcitabine and nab-paclitaxel; the second-line groups received mFOLFOX. The dose-expansion groups concerned first-line metastatic disease and included gemcitabine plus nab-paclitaxel alone, the same chemotherapy with oleclumab 3000 mg, and the combination with both oleclumab 3000 mg and durvalumab.
The listed treatment descriptions specify intravenous administration and some dosing schedules, but parts of those descriptions are truncated in the registry record. The complete treatment duration and all stopping rules are therefore not reported in the registry record. The record identifies randomization but does not report the randomization method, allocation ratio, concealment procedures, or whether particular groups were intended as direct comparators. Masking is listed as none.
The primary outcome concerns TEAEs and TESAEs during dose escalation, with a timeframe of Day 1 through 65.7 weeks (maximum observed duration). Safety results are also listed for dose expansion, along with response, disease control, and overall survival outcomes. The outcome-specific estimates, statistical comparison plan, and detailed analysis methods are not reported in the registry record. Consequently, the design description establishes the treatment groups and broad study structure but does not by itself establish the strength of any treatment comparison.
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: A total of 25 participants were treated in dose escalation part of this study. A total of 188 participants were randomised in dose expansion part of this study of which 170 participants were treated (18 participants were randomised but not treated). Results are presented for 195 treated participants only.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Dose-expansion, Gemcitabine + Nab-paclitaxel | Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel |
|---|---|---|---|---|---|---|
| STARTED | 7 | 7 | 3 | 8 | 62 | 38 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 7 | 7 | 3 | 8 | 62 | 38 |
Reasons for not completing this period:
| Reason | Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Dose-expansion, Gemcitabine + Nab-paclitaxel | Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel |
|---|---|---|---|---|---|---|
| Death | 7 | 7 | 3 | 8 | 47 | 32 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 4 | 2 |
| Sponsor decision | 0 | 0 | 0 | 0 | 9 | 4 |
| Reasons | 0 | 0 | 0 | 0 | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
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: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Dose-expansion, Gemcitabine + Nab-paclitaxel | Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel |
|---|---|---|---|---|---|---|---|
| Participants analysed | 7 | 7 | 3 | 8 | 62 | 38 | |
| Age, Continuous | Years | 66.7 (SD 12.8) | 59.6 (SD 11.4) | 67.0 (SD 14.9) | 64.8 (SD 4.8) | 65.6 (SD 8.0) | 62.5 (SD 11.1) |
| Sex: Female, Male: Female | Participants | 3 | 4 | 1 | 4 | 26 | 17 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 2 | 4 | 36 | 21 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 7 | 3 | 7 | 61 | 37 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 5 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 2 | 3 | 2 |
| Race (NIH/OMB): White | Participants | 6 | 5 | 3 | 6 | 54 | 33 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase, measured over Day 1 through 65.7 weeks (maximum observed duration).
| 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 TEAEs and TESAEs in the dose-escalation phase. A TEAE is an event absent at baseline that emerged after study drug administration, or an event present at baseline that worsened in intensity after administration. An adverse event is an untoward medical occurrence in someone who received study drug, without requiring that the event be judged caused by the drug.
A serious adverse event is an event resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or a congenital anomaly; an event may also be deemed serious for another significant reason. These definitions identify events by timing and seriousness, not by proof of treatment causation.
Counting participants with events is useful for describing how many people in a treatment group experienced a safety event. The registry’s primary outcome is a count, rather than a time-to-event endpoint or a measure of event severity over time. The stated observation period is Day 1 through 65.7 weeks (maximum observed duration), so exposure and follow-up can matter when interpreting counts. The registry defines the primary analysis population as as-treated: participants who received any study drugs, analyzed according to the treatment they actually received. It does not report a single combined estimate or an inferential comparison for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results give participant counts separately for dose-escalation and dose-expansion groups. They distinguish participants with serious adverse events from those with other treatment-emergent adverse events, and also list deaths by group. These are descriptive counts. Without a reported statistical comparison, confidence interval, or outcome-specific analysis method, the counts do not establish whether differences between groups are more than could arise from sampling variability.
In dose escalation, serious adverse events were reported for 4 participants in the oleclumab 1500 mg, durvalumab, gemcitabine, and nab-paclitaxel group, out of 7 at risk. The corresponding count was 6 out of 7 in the oleclumab 3000 mg regimen with the same accompanying drugs. In the mFOLFOX groups, the serious-event counts were 0 out of 3 for oleclumab 1500 mg with durvalumab and 4 out of 8 for oleclumab 3000 mg with durvalumab. These small group counts are descriptive and are not a reliable basis for ranking regimens.
In dose expansion, serious adverse events were reported for 34 participants out of 62 at risk with gemcitabine plus nab-paclitaxel, 24 out of 38 with added oleclumab 3000 mg, and 37 out of 70 with added oleclumab 3000 mg and durvalumab. The registry also reports other TEAEs for 60 out of 62, 36 out of 38, and 70 out of 70 participants in those groups, respectively. These categories should not be treated as mutually exclusive unless the registry says so; no such rule is reported. The listed deaths are counts, and the registry does not establish in this outcome record that each death was caused by treatment.
The registry lists pyrexia, pneumonia, acute kidney injury, and vomiting at 28.6% each among the top serious adverse event terms, followed by nausea at 25.0% and cellulitis at 14.3%. The denominators and event-counting details behind these percentages are not reported in the registry record, so their precision and comparability across groups cannot be assessed from these registry entries alone.
Although the study also lists response, disease control, and survival outcomes, the corresponding results are not reported in the registry record. The safety findings therefore should not be used as evidence about antitumor activity. The posted data describe events observed in the recorded groups; they do not, on their own, demonstrate that one regimen is safer or more effective than another.
9. Statistical Methods Explained
The outcome is a participant count. This is a straightforward descriptive measure: it records how many people in a group met the event definition during the stated observation period. A count is not the same as the total number of event episodes, because a participant may experience more than one event. The registry reports participant counts for serious events and other TEAEs, but does not report episode counts or clarify whether its event categories overlap.
What does a count tell the reader?
A count communicates the observed burden within the recorded group. To compare groups fairly, readers also need the number of participants who were eligible for the event count, the follow-up period, and information about exposure. The safety results include at-risk counts by group. However, the registry does not provide a participant-level account of duration on treatment or follow-up for each group in the registry record. Counts can therefore reflect both event occurrence and differences in observation or exposure.
General statistical explanation: a confidence interval expresses uncertainty around an estimate. It can help readers distinguish a precise estimate from one that remains compatible with a wide range of underlying values. No confidence intervals for the primary safety outcome are reported in the registry record. No p-value or other inferential comparison for the primary outcome is reported either. The displayed counts should consequently be read as descriptions, not as a formal test of differences.
Why does the group structure matter?
The study has dose-escalation and dose-expansion groups, with different chemotherapy regimens and disease-line settings. The dose-escalation groups include both gemcitabine plus nab-paclitaxel and mFOLFOX combinations, whereas the listed dose-expansion groups concern gemcitabine plus nab-paclitaxel. This means that an overall comparison across all groups could mix differences in chemotherapy, treatment phase, and patient setting. The registry does not report a prespecified pooled safety comparison or explain which groups should be treated as direct comparators.
Randomization can support causal comparisons when the allocation process and analysis preserve the randomized groups and the intended comparison is clearly defined. Here, the record lists the study as randomized but does not report the randomization procedure or allocation ratio. The primary safety population is as-treated, meaning participants are analyzed according to treatment actually received. General statistical explanation: analyzing participants by treatment received may no longer preserve the balance that randomization is intended to create, particularly if received treatment differs from assigned treatment. The record does not describe whether such differences occurred, so their presence or impact cannot be inferred.
Why does over-dispersion matter for count data?
General statistical explanation: some count outcomes vary more across participants or groups than a simple count model assumes. This extra variability is called over-dispersion. If it is present and ignored, standard errors can be too small and uncertainty can be understated. The current primary outcome is framed as the number of participants with events, rather than a count of recurrent event episodes. The registry does not report a model for recurrent events, an over-dispersion assessment, or a statistical model for the primary endpoint. It would therefore be inappropriate to claim that such a model was used or that over-dispersion was evaluated.
General statistical explanation: for a binary participant-level outcome, analysis may use the number with an event and the group denominator to estimate a risk or compare groups. Such an analysis requires a defined event threshold, a specified population, and a suitable approach to uncertainty. Although the registry provides counts and at-risk group sizes for safety categories, it does not report an adjusted or unadjusted effect estimate for the primary outcome. No new risk estimates or group differences are calculated in this interpretation.
What can be inferred from the listed outcomes?
The registry lists 29 outcome measures and 18 analyses. It identifies secondary outcomes involving TEAEs, abnormal vital signs, abnormal ECG parameters, abnormal clinical laboratory parameters, response, disease control, and overall survival. The details of those results are not reported in the registry record. The number of listed outcomes makes it important to know which outcomes were prespecified as primary, how comparisons were selected, and whether multiplicity was addressed. Those inferential details are not reported.
The record gives planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. These are planning assumptions, not evidence of the trial’s original design or observed power. The registry does not report that these assumptions were used to design this study, nor does it report a sample-size justification for the primary safety endpoint. The actual estimates for the illustrations are not included in the registry record. They should not be interpreted as observed treatment effects or as the trial’s statistical analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including safety outcomes, response and disease control in dose escalation, and overall survival outcomes in dose expansion. When many outcomes or comparisons are examined, the chance of a nominally notable finding arising by chance can increase. General statistical explanation: multiplicity procedures can control or describe that concern, but their use depends on the planned family of hypotheses and the intended interpretation.
The registry record does not report a multiplicity strategy, a hierarchy for testing outcomes, or which treatment contrasts were intended to be confirmatory. It also does not report a statistical analysis plan for the listed outcomes. Therefore, the safety counts should not be read as proof of a prespecified statistically significant difference, and unreported efficacy results cannot be inferred from the outcome list.
Missing-data handling is not reported in the registry record. The primary analysis population is described as as-treated and includes participants who received any study drugs, analyzed according to treatment actually received. The record does not state how participants with incomplete safety follow-up, missing outcome assessments, or treatment discontinuation were handled. It also does not report whether missingness was assessed or whether sensitivity analyses were performed.
The primary endpoint is restricted to the dose-escalation phase, while safety outcomes are also listed for dose expansion. The registry does not report how these populations relate to the randomized allocation for each analysis or whether all randomized participants were included in any particular outcome analysis. These omissions limit assessment of attrition, analysis-population consistency, and the impact of missing data.
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 |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 4 | 7 | 57.1% |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 6 | 7 | 85.7% |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | 0 | 3 | 0.0% |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | 4 | 8 | 50.0% |
| Dose-expansion, Gemcitabine + Nab-paclitaxel | 34 | 62 | 54.8% |
| Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel | 24 | 38 | 63.2% |
| Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 37 | 70 | 52.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 7 of 7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 7 of 7 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | 3 of 3 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | 8 of 8 |
| Dose-expansion, Gemcitabine + Nab-paclitaxel | 47 of 62 |
| Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel | 32 of 38 |
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 |
|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 7 of 7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 7 of 7 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | 3 of 3 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | 8 of 8 |
| Dose-expansion, Gemcitabine + Nab-paclitaxel | 60 of 62 |
| Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel | 36 of 38 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Dose-expansion, Gemcitabine + Nab-paclitaxel | Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 7 | 2 of 7 | 0 of 3 | 0 of 8 | 5 of 62 | 3 of 38 |
| Vomiting | Gastrointestinal disorders | 0 of 7 | 2 of 7 | 0 of 3 | 1 of 8 | 5 of 62 | 0 of 38 |
| Pneumonia | Infections and infestations | 2 of 7 | 0 of 7 | 0 of 3 | 0 of 8 | 3 of 62 | 2 of 38 |
| Nausea | Gastrointestinal disorders | 0 of 7 | 0 of 7 | 0 of 3 | 2 of 8 | 4 of 62 | 0 of 38 |
| Sepsis | Infections and infestations | 0 of 7 | 1 of 7 | 0 of 3 | 0 of 8 | 4 of 62 | 0 of 38 |
| Cellulitis | Infections and infestations | 1 of 7 | 0 of 7 | 0 of 3 | 0 of 8 | 1 of 62 | 2 of 38 |
| Colitis | Gastrointestinal disorders | 0 of 7 | 0 of 7 | 0 of 3 | 0 of 8 | 3 of 62 | 1 of 38 |
| Biliary obstruction | Hepatobiliary disorders | 0 of 7 | 0 of 7 | 0 of 3 | 0 of 8 | 2 of 62 | 1 of 38 |
| Failure to thrive | Metabolism and nutrition disorders | 0 of 7 | 0 of 7 | 0 of 3 | 1 of 8 | 1 of 62 | 1 of 38 |
| Acute kidney injury | Renal and urinary disorders | 0 of 7 | 2 of 7 | 0 of 3 | 0 of 8 | 0 of 62 | 1 of 38 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Dose-expansion, Gemcitabine + Nab-paclitaxel | Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 6 of 7 | 7 of 7 | 2 of 3 | 6 of 8 | 30 of 62 | 25 of 38 |
| Nausea | Gastrointestinal disorders | 6 of 7 | 6 of 7 | 2 of 3 | 4 of 8 | 26 of 62 | 26 of 38 |
| Diarrhoea | Gastrointestinal disorders | 5 of 7 | 2 of 7 | 1 of 3 | 5 of 8 | 18 of 62 | 14 of 38 |
| Neutropenia | Blood and lymphatic system disorders | 2 of 7 | 2 of 7 | 2 of 3 | 1 of 8 | 22 of 62 | 14 of 38 |
| Decreased appetite | Metabolism and nutrition disorders | 4 of 7 | 3 of 7 | 1 of 3 | 3 of 8 | 16 of 62 | 15 of 38 |
| Anaemia | Blood and lymphatic system disorders | 3 of 7 | 3 of 7 | 1 of 3 | 0 of 8 | 17 of 62 | 14 of 38 |
| Constipation | Gastrointestinal disorders | 2 of 7 | 5 of 7 | 2 of 3 | 2 of 8 | 10 of 62 | 15 of 38 |
| Vomiting | Gastrointestinal disorders | 3 of 7 | 2 of 7 | 1 of 3 | 3 of 8 | 15 of 62 | 12 of 38 |
| Neutrophil count decreased | Investigations | 0 of 7 | 2 of 7 | 1 of 3 | 3 of 8 | 19 of 62 | 8 of 38 |
| Oedema peripheral | General disorders | 2 of 7 | 3 of 7 | 0 of 3 | 2 of 8 | 13 of 62 | 12 of 38 |
Serious events with the highest arm-level rate: pyrexia (28.6%), pneumonia (28.6%), acute kidney injury (28.6%), vomiting (28.6%), nausea (25.0%).
For each group, the registry reports the number at risk and the number of participants with serious adverse events, other TEAEs, and deaths. For example, in the dose-escalation group receiving oleclumab 1500 mg with durvalumab, gemcitabine, and nab-paclitaxel, 4 of 7 participants had serious adverse events and 7 of 7 had other TEAEs; the listed death count is 7. The corresponding dose-escalation group with oleclumab 3000 mg reports 6 of 7 with serious events, 7 of 7 with other TEAEs, and 7 deaths.
These are participant counts, not event rates adjusted for time on treatment. A serious adverse event is defined by specified consequences or clinical significance, while a TEAE is defined by timing and worsening after study drug administration. Seriousness does not itself show that treatment caused the event. The registry’s adverse-event definition explicitly does not require a causal relationship.
Deaths are listed separately from serious adverse events and other TEAEs. The registry record does not report that the listed deaths were treatment-related, nor does it provide a causal assessment in the registry record. The figures should be read as descriptive safety information by recorded treatment group, not as comparative proof that a regimen caused more or fewer harms.
12. What the Result Does, and Does Not, Mean
The posted results establish that participants in the listed groups experienced treatment-emergent and serious adverse events, and they give participant counts for those categories. They also provide counts of deaths and selected serious adverse event terms. These observations are relevant to describing the safety experience recorded during the study, but the counts alone do not establish why an event occurred or whether one regimen differs from another.
The primary outcome is safety-focused and applies to dose escalation. It does not measure tumor shrinkage, disease control, or survival. The registry lists response and disease-control outcomes in dose escalation and overall survival outcomes in dose expansion, but results for those outcomes are not reported in the registry record. No conclusion about antitumor activity or survival can be drawn from the safety counts.
General statistical explanation: an observed difference between groups can reflect a true treatment effect, random variation, differences in follow-up, or other features of the groups. A formal interpretation normally considers the estimate, its uncertainty, the planned comparison, and the analysis population. Those inferential elements are not reported for the primary outcome in the registry record. No treatment effect or uncertainty interval is therefore available to support a comparative claim.
The trial’s randomized designation is important context, but the primary analysis is as-treated and the allocation details are not reported. The regimen groups also differ by chemotherapy and treatment phase. Accordingly, the descriptive results should not be treated as a direct head-to-head ranking of all listed regimens. They also should not be interpreted as medical advice or as evidence that any treatment works or does not work.
13. Why This Trial Matters Statistically
This study is statistically notable for bringing several treatment combinations and study phases into one randomized, parallel-group record. The dose-escalation groups differ in oleclumab dose and chemotherapy regimen, and the dose-expansion groups add comparisons involving oleclumab and durvalumab with gemcitabine plus nab-paclitaxel. That structure makes the definition of each comparison essential: a group-level safety count has meaning in relation to its treatment, disease-line setting, and analysis population.
The primary endpoint is a count of participants with TEAEs and TESAEs, rather than a single efficacy measure. Counts are valuable for describing the observed safety experience, while their interpretation depends on group sizes, follow-up, event definitions, and uncertainty. The registry records at-risk counts but does not report inferential estimates for the primary outcome. This illustrates why descriptive safety results should be distinguished from comparative statistical evidence.
The as-treated analysis population also matters. General statistical explanation: randomization is intended to make treatment groups comparable at assignment; an analysis based on treatment received can depart from that assignment-based comparison. The registry does not report enough allocation or treatment-received detail to assess whether this issue affected the findings.
Finally, the record lists many outcomes, including response, disease control, and survival, but their results and the multiplicity approach are not reported in the registry record. The distinction between an outcome being listed and an outcome having an interpretable result is important. The record supports a description of safety counts, but not a conclusion about comparative efficacy or a definitive statistical ranking of the regimens.
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 available registry information does not report a detailed statistical analysis plan, the randomization procedure, the allocation ratio, or the intended pairwise comparisons. This restricts assessment of how the randomized design maps to the reported treatment groups and whether the analysis followed the planned assignment.
The primary analysis uses an as-treated population. The registry does not report the corresponding assignment-based population results or explain whether treatment received differed from treatment assigned. It also does not report missing-data rules, completeness of follow-up by group, exposure duration by group, or sensitivity analyses. Those details would help assess whether differences in observed counts reflect differences in event experience or in observation.
The safety outcome is reported as participant counts. Event episode counts, recurrent-event methods, group-level uncertainty estimates, and formal tests are not reported. The listed serious adverse event terms have percentages, but the relevant denominators and event-counting details are not reported in the registry record. These limitations prevent assessment of precision and of comparability between the term percentages and group-level counts.
The registry includes response, disease-control, and survival outcomes, but their results are not reported in the registry record. It also does not report how multiplicity across the many outcomes was addressed. Parts of the treatment descriptions are truncated, limiting detail about full regimens and stopping rules. These limitations are specific to interpreting this record; they do not establish that analyses or procedures were absent from the conduct of the study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study. — NCT03611556.
- Registry record last updated 2023-10-03; status last verified 2023-09.
- Results first posted 2023-10-03.
- 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
NCT03611556 is a completed randomized, non-masked, parallel Phase 1b/2 study sponsored by MedImmune LLC. It enrolled 213 participants with metastatic pancreatic ductal adenocarcinoma. Recorded study dates are 2018-06-21 for start and 2022-07-22 for primary completion.
The study evaluated oleclumab with chemotherapy, with or without durvalumab, across dose-escalation and dose-expansion groups. Chemotherapy regimens included gemcitabine plus nab-paclitaxel and mFOLFOX. The primary outcome counted participants with TEAEs and TESAEs during Day 1 through 65.7 weeks (maximum observed duration), using an as-treated population.
The registry reports safety counts by group and lists additional safety, response, disease-control, and survival outcomes. Detailed efficacy results, inferential comparisons, missing-data procedures, and a multiplicity strategy are not reported in the registry record.