A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers (NCT02643303), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Subjects With Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The clinical question is therefore mainly about the safety experience of the study regimens in a varied, biopsy-accessible cancer population, alongside planned assessments of tumor response and time-to-event outcomes. The registry record does not establish a comparative question against standard care or another control regimen. It also does not provide a single efficacy estimate that can be interpreted across all cancer types. The cohort structure reflects the inclusion of multiple disease groups and treatment schedules; findings for one group should not automatically be extended to another.

3. Trial Design

This was an open-label, multicenter Phase 1/2 study with non-randomized allocation and a parallel-group model. The registry record reports an enrollment of 58 and a completed status. The recorded start date is 2016-12-28, and the primary completion date is 2022-02-23. The study concerned people with advanced, measurable, biopsy-accessible cancers.

The treatment approach combined durvalumab, an intravenous PD-L1 antibody, with poly-ICLC, a TLR3 agonist described as a tumor microenvironment modulator. Tremelimumab, a CTLA-4 antibody, was included in some cohorts. The cohort descriptions indicate that schedules and routes varied: durvalumab was described as intravenous, poly-ICLC as intratumoral and intramuscular, and tremelimumab as intravenous in one cohort and intratumoral in other cohort descriptions. The available descriptions are incomplete in places, so the full schedule for every cohort is not reported in the registry record.

The listed groups include Phase 1 Cohorts 1A and 1B, and Cohort 1C plus Phase 2 groups for head and neck squamous cell carcinoma, locally recurrent or metastatic breast cancer, sarcoma, Merkel cell carcinoma, melanoma after failure of available therapies, genitourinary cancers with accessible metastases, and solid tumors with accessible masses. Cutaneous T-cell lymphoma is also among the listed conditions, although a corresponding cohort label is not included in the posted arm descriptions. No randomized allocation is reported, and the cohort sizes differ. These features make the design useful for describing experience across cohorts, but not for estimating a randomized comparison between treatment strategies.

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: The Phase 1 Cohort 1C dosing regimen was used in Phase 2 without any dose modifications. As indicated in the protocol, the subjects enrolled in Cohort 1C are included in the appropriate Phase 2 cohort based on tumor type. For this reason, Cohort 1C is not presented separately.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who received at least one dose of study treatment.

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 subjects who received at least one dose of study medication.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Treatment-emergent Adverse Events (TEAEs), measured over up to 15 months.

The primary endpoint was the number of participants with treatment-emergent adverse events, assessed up to 15 months. A treatment-emergent event was defined as one that occurred or worsened after the first dose of study treatment. Adverse events were collected from signing informed consent through 90 days after the last dose, using clinical laboratory tests, vital signs, physical examinations and other medically indicated assessments, including subject interviews. Toxicity grading followed National Cancer Institute CTCAE version 4.03.

A participant-count endpoint is useful in a safety-focused study because it records how many participants experienced an event, rather than only describing event counts. A participant may experience more than one event, so a count of affected participants and a count of all events answer different questions. General statistical context: participant-level summaries help describe the proportion of the enrolled safety population with at least one event, while event-level summaries can convey recurrence or burden. Neither alone describes severity, timing or causal attribution completely.

The registry record identifies the safety population as all subjects who received at least one dose. However, a numerical result for the stated primary endpoint is not reported in the registry record. The posted cohort safety data include counts for serious adverse events and other adverse events, but those entries are not an explicit overall numerical result for the primary treatment-emergent adverse-event endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant-count safety endpoint and lists several tumor-response and time-to-event outcomes. It does not report a statistical analysis plan, analysis methods for the primary safety endpoint, or numerical efficacy results. The distinctions below explain the methods named in the record and what they can generally contribute; they should not be mistaken for evidence that a particular unreported analysis was performed.

What does a participant count describe?

For the primary endpoint, the intended quantity is the number of participants who experienced at least one treatment-emergent adverse event. This is different from counting every event. If a participant has repeated events, a participant-level count still counts that person once, whereas an event-level tally can include multiple occurrences. General statistical context: an event proportion is easier to interpret when its population and observation period are explicit. Here, the record defines the safety population as people who received at least one dose and specifies event collection from informed consent through 90 days after the last dose. The endpoint timeframe is stated as up to 15 months. The numerical result for the primary endpoint is not reported in the registry record.

How should the response criteria be understood?

The secondary outcomes name RECIST 1.1 and immune-related RECIST, or irRECIST. These are response-assessment frameworks used to classify tumor response and disease control. The registry lists a best overall tumor response outcome under RECIST 1.1, as well as overall disease control under both RECIST 1.1 and irRECIST. The record does not provide numerical category counts or response estimates for these outcomes. It also does not report details of assessment timing, review procedures, or whether response assessments were performed by investigators or an independent review process.

What does Kaplan-Meier estimation do?

The registry names Kaplan-Meier estimation for median progression-free survival under irRECIST and RECIST 1.1, and for median overall survival. General statistical context: the Kaplan-Meier method estimates the probability of remaining free of an event over time while accounting for participants whose event status is not yet known at the end of observation or who leave observation earlier. The median is the time at which the estimated event-free probability reaches a specified point in the distribution, if that point is reached. A median cannot be read without knowing the event definition, follow-up and censoring context. The registry record does not report numerical medians, confidence intervals, event counts for these outcomes, or detailed censoring rules.

Progression-free survival depends on how progression and death are defined and assessed. Overall survival concerns time to death, but the record does not provide a numerical estimate or analysis details. General statistical context: a time-to-event estimate is not simply a count of participants with an event; it uses the timing of events and censoring information. Interpretation is stronger when the event definition, follow-up, number at risk over time and uncertainty intervals are available. Those numerical details are not reported in the registry record.

What can the cohort safety counts establish?

The safety entries give counts of participants at risk and affected by serious adverse events, other adverse events, and deaths for each cohort. These counts describe what was recorded within those groups. They are not adjusted comparisons, and the design has no randomized control group. General statistical context: small cohorts tend to yield unstable estimates, because a small change in the number of affected participants can substantially change a proportion. The registry record does not report confidence intervals for the cohort safety counts or a model adjusting for differences between groups.

The record states that toxicity was graded under CTCAE version 4.03 and that adverse events were based on clinical assessments and other medically indicated evaluations. It does not report the full grading distribution, event-level timing, relatedness assessments, or a detailed rule for attributing events to treatment. The serious-event terms and percentages are presented, but their denominators are not reported in the registry record.

No analysis count is listed, and no statistical tests or confidence intervals for the outcomes are reported. Thus, the methods named in the registry establish which kinds of outcomes were planned, but the record does not provide enough results to assess their estimated magnitude or precision. The treatment schedules, disease groups and cohort sizes also differ, which limits descriptive comparisons even before considering statistical uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: disease control under irRECIST and RECIST 1.1, best overall tumor response under RECIST 1.1, progression-free survival under each of the two response frameworks, and overall survival. These outcomes create multiple opportunities to examine results. A statistical plan describing how multiplicity was handled is not reported in the registry record. It is also not reported whether any outcome was designated as a key secondary endpoint for confirmatory interpretation or whether formal hypothesis tests were planned.

General statistical context: when many outcomes are tested, the chance of observing an apparently notable result by chance can increase if each test is judged separately. Prespecified adjustment or a clear exploratory interpretation can help readers understand that issue. Because the registry record lists no analyses and gives no numerical efficacy outcomes, multiplicity-adjusted or unadjusted efficacy conclusions cannot be assessed.

Missing-data methods are not reported in the registry record. For response outcomes, the record does not explain how participants without an evaluable post-baseline assessment were handled. For survival outcomes, it does not provide censoring rules, follow-up summaries, or the number of participants at risk over time. For safety, it identifies a population of participants who received at least one dose, but it does not report an explicit overall primary-endpoint result or details of missing safety assessments.

Analysis populations are only partly described. The primary safety population is all subjects who received at least one dose. The record does not report the analysis population definitions for the response and survival endpoints, nor whether all enrolled participants, treated participants, or another group contributed to each analysis. A sample-size justification, planned interim analyses, and the statistical plan are not reported in the registry record. Those omissions prevent assessment of planned precision, stopping rules, or how incomplete observations may have affected the reported outcomes.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (66.7%), malignant neoplasm progression (66.7%), dyspnoea (33.3%), abdominal pain (25.0%), asthenia (25.0%).

The serious-adverse-event entries are counts within each cohort, not a comparison of treatment with a control group. They should be read alongside the cohort-specific numbers at risk: the recorded serious-event counts range from 0 of 1 in the head and neck squamous cell carcinoma group and 0 of 4 in Phase 1 Cohort 1A to 4 of 15 in the breast cancer group. The other listed cohort counts are 3 of 5, 3 of 7, 2 of 4, 3 of 10, 2 of 3 and 2 of 7. The groups are small and vary in size, so apparent differences can be sensitive to individual observations.

The record separately lists deaths by cohort. Those counts should not be interpreted as treatment-related deaths: causal attribution is not stated in these entries. The serious-event terms include Sepsis and Malignant neoplasm progression, each reported as 66.7%, as well as Dyspnoea at 33.3%, Abdominal pain and Asthenia at 25.0%, and Anaemia at 20.0%. The denominators and event-level context for these percentages are not reported in the registry record. A percentage for an event term is not necessarily the same as the proportion of participants with any serious adverse event.

Safety summaries also do not establish whether an event was caused by treatment. The registry describes how adverse events were collected and graded, but detailed relatedness, timing and severity distributions are not reported in the registry record.

12. What the Result Does, and Does Not, Mean

The record documents a completed, non-randomized Phase 1/2 study of durvalumab and poly-ICLC, with tremelimumab included in some cohorts, among people with several types of advanced, measurable, biopsy-accessible cancer. Its cohort-level safety entries show serious adverse events recorded in multiple groups, with counts varying by cohort. The record also reports that other adverse events affected all participants in each listed group. These are descriptive observations from the posted results, not evidence that one cohort’s regimen is safer or less safe than another’s.

The primary endpoint is defined as the number of participants with treatment-emergent adverse events, but its numerical result is not reported in the registry record. The secondary outcomes include tumor response, disease control, progression-free survival and overall survival. Their numerical results are also not reported in the registry record. Without those estimates and measures of uncertainty, readers cannot assess the magnitude or precision of any efficacy outcome from this record.

The data do not establish that the treatments caused the recorded events or deaths. Nor do they show whether the treatment combinations improve tumor response, disease control, progression-free survival or overall survival. Those conclusions would require reported outcome estimates and appropriate context; a non-randomized design also limits causal comparisons. The treatment regimens and cancer groups differ across cohorts, and there is no randomized control group for comparison.

General statistical context: an observed count is a description of the participants followed in a study, while a treatment effect is a comparison designed to distinguish treatment differences from chance and other differences between groups. The registry information supports the former more than the latter. It therefore offers a limited descriptive account of safety, but not a basis for a firm comparative efficacy or causal conclusion.

13. Why This Trial Matters Statistically

This study raises a set of statistical issues common to early-phase trials that enroll people with different cancers and use evolving treatment cohorts. The registry combines a safety-focused primary endpoint with tumor-response and time-to-event outcomes. That combination makes it important to distinguish what is defined as an endpoint from what has a numerical result available. Here, the endpoint definitions and analysis methods are partly described, but the primary endpoint result and the listed efficacy estimates are not reported in the registry record.

The cohort structure also matters. A non-randomized design can describe safety and outcomes within treated groups, but differences between groups may reflect differences in disease type, cohort eligibility or treatment schedule as well as treatment itself. The registry does not offer a randomized comparison that could balance such factors. Cohort sizes are small and unequal, so individual observations can have considerable influence on the descriptive counts.

Safety interpretation depends on the distinction between affected participants and event occurrences, and on details such as severity, timing and attribution. The registry gives selected cohort-level counts and serious-event terms, while not reporting the primary treatment-emergent adverse-event count or full event-level context. For efficacy, Kaplan-Meier methods are named, but the necessary estimates, uncertainty intervals and follow-up details are not included.

These limitations do not make the record uninformative: it identifies the study population, treatment approach, endpoint definitions and selected safety observations. They do mean that a statistically careful reading must avoid converting descriptive cohort counts into comparative effects or treating planned outcomes as demonstrated results.

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 registry record reports an enrollment of 58, but the cohort-level safety groups are small and uneven. The study is non-randomized and open-label, with no like-for-like control comparison. Different cohorts represent different cancer groups and treatment schedules, so direct comparisons would be confounded by differences in population and regimen. The record does not report adjusted comparisons that address those differences.

The primary endpoint is specified, but its numerical result is not reported in the registry record. Secondary response and survival outcomes are listed without numerical estimates. Confidence intervals, p-values, full response distributions and follow-up details are not reported. The registry states that Kaplan-Meier estimation was used for certain medians, but it does not provide those medians or the supporting event and censoring information.

The safety entries are limited to cohort counts, death counts and selected serious-event terms. The registry does not report the denominator for the serious-event percentages, full event-level timing, detailed severity distributions, or complete treatment-relatedness assessments. The record describes data collection and grading, but the resulting detail needed to characterize the full safety profile is not available in the reported entries.

Some arm descriptions are truncated, and the complete dosing schedule for every cohort is not reported in the registry record. The record also does not report the statistical analysis plan, multiplicity approach, missing-data methods, analysis populations for efficacy outcomes, sample-size justification or interim-analysis plan. These gaps restrict assessment of precision, completeness and the intended interpretation of the outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers — NCT02643303.
• Registry record last updated 2022-12-02; status last verified 2022-11.
• Results first posted 2022-12-02.
• 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.

18. Record Summary

The registry record describes a completed, open-label, non-randomized Phase 1/2 study of durvalumab and poly-ICLC, with tremelimumab in some cohorts, in advanced, measurable, biopsy-accessible cancers. Enrollment was 58. Cohorts covered several cancer groups and used different treatment schedules.

The primary endpoint was the number of participants with treatment-emergent adverse events, assessed up to 15 months, with toxicity graded under CTCAE version 4.03. The numerical result for that endpoint is not reported in the registry record. Cohort-level serious-adverse-event counts, other-adverse-event counts, death counts and selected serious-event terms are reported. The listed response, disease-control and survival outcomes have no numerical results reported in the registry record.

Because the study was non-randomized, had no control group, and included small, differing cohorts, the posted safety counts are descriptive rather than comparative treatment-effect estimates.