A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors (NCT02718911), a non-randomized phase 1 study. The primary outcome is Recommended Phase 2 Dose of LY3022855 Combined With Durvalumab (Maximum Tolerated Dose [MTD]).

2. Clinical Question

3. Trial Design

This was a phase 1, non-randomized, unmasked, sequential trial. It evaluated LY3022855 in combination with durvalumab or tremelimumab in participants with advanced solid tumors. The study is marked completed, with enrollment of 72. The registry lists a start date of 2016-06-16 and a primary completion date of 2018-12-14.

The design included dose escalation and expansion. In dose escalation, cohorts received combinations at different stated doses. For the durvalumab combination, the listed escalation cohorts included LY3022855 doses of 25 mg, 50 mg, 75 mg, and 100 mg, with durvalumab at 750 mg. For tremelimumab, the listed cohorts varied LY3022855 and tremelimumab doses. The expansion description includes NSCLC and ovarian cancer cohorts receiving LY3022855 with durvalumab. The registry descriptions are not complete for every cohort, so further regimen details are not reported in the registry record.

Sequential dose escalation is intended to evaluate dose levels in an ordered process, rather than assigning participants at random among concurrent comparison groups. The registry does not report enough detail to reconstruct the escalation rules or the number of participants enrolled at every dose for the primary endpoint. It also does not report a randomized comparator. The displayed safety cohorts therefore describe observations within groups, not controlled estimates of differences between treatments.

The stated primary endpoint concerns the recommended phase 2 dose of LY3022855 with durvalumab, based on DLT assessment and the registry’s MTD definition, during Cycle 1 (4 weeks). Secondary outcomes include response and disease control rates, antibody counts, and pharmacokinetic measures. Their listed presence does not by itself show that results were posted. No analysis results are available in the posted analysis set, and the numerical primary endpoint result is 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: This study has two parts: Part A: Dose-escalation of LY3022855 combined with durvalumab or tremelimumab. Part B: Dose-expansion of LY3022855 combined with durvalumab.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug LY3022855 + Durvalumab.

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 participants who received at least one dose of study drug.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Recommended Phase 2 Dose of LY3022855 Combined With Durvalumab (Maximum Tolerated Dose [MTD]), measured over Cycle 1 (4 weeks).

The primary endpoint is the recommended phase 2 dose of LY3022855 when combined with durvalumab, expressed in milligrams. The registry says the dose recommendation was based on dose-limiting toxicity assessment and the maximum tolerated dose definition over Cycle 1 (4 weeks). It defines the MTD as the highest tested dose with less than 33% probability of causing a DLT. The endpoint population is participants who received at least one dose of LY3022855 with durvalumab.

In general, a dose-finding endpoint is used in early-phase research to identify a dose that can be taken forward for further study while accounting for toxicity observed during the specified assessment period. It is not an efficacy endpoint: a dose recommendation does not establish whether a treatment improves tumor outcomes. The registry also lists response, disease control, antibody, and pharmacokinetic outcomes as secondary measures, but numerical results for these are not reported in the registry record.

The primary endpoint is stated as a dose-selection outcome, but the posted record does not give the recommended dose or the underlying DLT counts used to reach it. Consequently, readers can describe the endpoint’s purpose and definition, but cannot verify the dose recommendation from the posted primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a sequential, non-randomized design imply?

In a randomized trial, assignment by chance is used to make comparison groups more alike, on average, with respect to measured and unmeasured characteristics. This study is described as non-randomized and sequential. Participants were therefore not assigned through random allocation to the listed cohorts. Cohort counts should be read as separate observations at dose levels or in expansion groups, not as if each cohort were a concurrent control for the others.

Sequential dose escalation is a common general approach in early-phase studies: investigators assess a dose level and use safety information to guide progression through planned dose levels. The registry record does not report the detailed escalation algorithm, stopping rules, or decision process for this study. The primary endpoint description does state that the dose recommendation used DLT assessment and an MTD definition, but it does not provide the numerical endpoint result or the DLT data needed to retrace the decision.

How should the MTD definition be read?

The record defines the MTD as the highest tested dose with less than 33% probability of causing a DLT. This is the study’s stated dose-selection criterion. In general, the probability in such a definition refers to an underlying risk that is estimated using observed toxicity and a statistical or decision procedure. A small cohort can leave considerable uncertainty about that risk. The record does not report the estimation procedure, prior assumptions, or uncertainty interval, so those details cannot be evaluated from the posted information.

The endpoint is specific to LY3022855 combined with durvalumab. It should not be treated as a reported dose recommendation for the tremelimumab combinations. Nor does identifying an MTD, by itself, establish that the selected dose is effective or the best balance of benefit and harm. It is a dose-finding outcome intended to inform later study.

What do the adverse-event counts show?

The posted safety data give the number at risk and the number affected in each cohort for serious adverse events and other adverse events. A count such as 1 of 5 is a direct description of the cohort’s reported participants; it is not an adjusted estimate of risk. In general, a proportion based on a small group is imprecise, and a single additional event can have a substantial effect on the displayed percentage. Follow-up time, event timing, severity grading, and attribution to treatment matter for interpretation, but the necessary detail is not reported in the registry record.

Seriousness and severity are distinct concepts in general safety reporting. Seriousness refers to specified consequences or criteria, whereas severity describes intensity. The registry’s serious-event counts should not be combined with the separate counts for other adverse events as if they were mutually exclusive categories. A participant may experience more than one event, and the record does not provide person-level overlap or event-level detail.

What can the sample-size illustrations say?

The accompanying sample-size section is a planning illustration computed from an observed effect, not the original trial design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations show what a hypothetical future comparison might require under selected assumptions. They do not describe the number of participants actually enrolled in this study, and they are not observed power.

The record is non-randomized and does not supply a like-for-like control comparison. A planning illustration based on an observed effect cannot repair that design limitation. It does not demonstrate that a future trial will achieve the assumed effect, nor does it validate the observed effect as unbiased. The figures should be read as conditional planning scenarios rather than evidence about the present study’s treatment effects.

Why are confidence intervals and analysis details important?

In general, a confidence interval expresses the precision of an estimate under a statistical model and sampling process. Narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. The registry record does not report confidence intervals for the safety counts, and the posted analysis set contains no analysis results. There is consequently no reported interval-based estimate to interpret for the primary endpoint or secondary outcomes.

The record does not report the statistical analysis plan, interim analyses, sample-size justification, or missing-data methods. Those omissions matter because analytic choices can influence how outcomes are summarized and which participants contribute to an estimate. They should not be filled in by assumption. The defensible interpretation is limited to the design features, endpoint definition, and descriptive counts that are actually posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: response rate, disease control rate, antibody counts, and pharmacokinetic measures. The record also has a primary dose-selection endpoint. Testing or estimating multiple outcomes can raise multiplicity concerns in general, because the chance of at least one apparently notable result can increase when many hypotheses are examined. Whether and how that issue was addressed is not reported in the registry record. No analysis results are present in the posted analysis set, so there are no reported inferential tests to assess for multiplicity adjustment.

The statistical analysis plan, including any prespecified hierarchy among outcomes or adjustment strategy, is not reported in the registry record. It is also not reported whether interim analyses were planned or conducted. The endpoint descriptions identify what the study intended to measure, but do not establish how each outcome was analyzed.

Missing-data handling is not reported in the registry record. The primary endpoint population is described as participants who received at least one dose of LY3022855 with durvalumab, but the posted record does not explain how missing toxicity assessments, discontinuations, or incomplete follow-up were handled. Nor does it provide denominators and follow-up detail for every secondary outcome. In general, missingness can affect an estimate when participants with unavailable outcomes differ systematically from those with observed outcomes.

The registry also does not report a full account of analysis populations for the secondary outcomes. Readers should therefore avoid assuming that all enrolled participants contributed to every analysis or that the same denominator was used for each endpoint. The available summaries support only cautious description of the posted counts and endpoint definitions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: confusional state (40.0%), anaemia (20.0%), hypothyroidism (20.0%), abdominal discomfort (20.0%), nausea (20.0%).

The safety display gives, for each cohort, the number at risk and the number affected by serious adverse events, other adverse events, and deaths. For instance, the durvalumab 100 mg dose-escalation cohort lists 1 of 5 participants affected by a serious adverse event, while the NSCLC expansion cohort lists 12 of 19. These counts describe what the registry reports for each group; they are not adjusted comparisons between regimens.

The record lists deaths in the cohort summaries, but those counts alone do not establish that the deaths were caused by study treatment. The event timing, circumstances, attribution, and participant-level overlap are not reported in the registry record. Likewise, the count of participants with other adverse events does not tell how many events each person experienced or their severity.

The registry lists serious-event terms with percentages: confusional state at 40.0%, and anaemia, hypothyroidism, abdominal discomfort, nausea, and vomiting at 20.0% each. The denominator used for these percentages is not reported in the registry record. Treat them as a brief listing of reported terms rather than a complete account of all harms or a basis for comparing cohorts.

In general, safety counts from small, non-randomized groups are descriptive and can be imprecise. They do not by themselves establish whether an event is more frequent under one combination than another.

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

The posted record establishes that this completed phase 1 study evaluated LY3022855 with durvalumab or tremelimumab in advanced solid tumors, using sequential dose cohorts and expansion groups. It states that the primary aim was to determine a recommended phase 2 dose of LY3022855 with durvalumab based on DLT assessment and an MTD definition. It also reports cohort-level safety counts and lists several planned secondary outcomes.

It does not report the numerical recommended dose, the underlying DLT results, or numerical results for the listed response, disease control, antibody, and pharmacokinetic outcomes. The record therefore does not establish a response rate, treatment effect, or comparative benefit. The absence of posted outcome figures is not evidence that an outcome did or did not occur; it means the registry record does not report those results.

The cohort safety counts can be read as descriptive observations, but not as estimates from randomized comparisons. The study was non-randomized, and the cohorts differed in regimen and in whether they were escalation or expansion groups. Without a like-for-like control, differences between their counts cannot be attributed to the drugs or doses. Counts of deaths and serious events likewise do not establish causation.

More generally, a phase 1 dose-finding result, even if fully reported, answers a different question from a later trial designed to estimate treatment benefit. A dose recommendation would guide further research; it would not establish efficacy or comparative safety. Here, because the primary numerical result is not reported, readers cannot verify even the stated dose-selection outcome from the posted record.

The interpretation is thus bounded: the registry documents the study’s design, endpoint intent, and selected safety summaries, while leaving key outcome and analysis details unavailable. The findings should not be extended to treatment decisions or to claims about effectiveness.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines dose escalation with expansion cohorts while evaluating two different immunotherapy combinations. That structure raises distinct interpretive questions: dose selection depends on toxicity observations across dose levels, whereas expansion cohorts can describe further experience in specified groups. The record identifies these elements but does not provide enough detail to reconstruct the dose-escalation decisions or the recommended dose.

The primary endpoint is a dose-finding outcome, not a conventional efficacy comparison. Its stated MTD threshold gives readers a criterion for understanding the intended decision, while the missing numerical result prevents assessment of what dose was selected or how much uncertainty surrounded that selection. This is a useful distinction between a clearly described endpoint and a result that can actually be evaluated.

The cohort-level adverse-event summaries also illustrate why design matters when reading numbers. Counts can be informative descriptions, but non-randomized cohorts with different regimens are not interchangeable comparison groups. Apparent differences in counts may reflect cohort composition, exposure, follow-up, or chance, as well as possible treatment effects. The registry summaries do not resolve those explanations.

Finally, the study underscores the difference between observed trial evidence and planning calculations. Sample-size illustrations can explore hypothetical future comparisons under stated assumptions, but they are not observed power and do not transform the current study into a randomized comparison. Keeping the dose-finding aim, descriptive safety data, missing outcome results, and planning scenarios separate is essential for statistically sound interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to interpreting this record. First, the study is non-randomized and sequential, with no reported randomized control group. The cohort summaries cannot support a like-for-like comparison of the combinations or dose levels. Second, the primary endpoint’s numerical result is not reported in the registry record, and the DLT counts and dose-selection analysis needed to verify the recommendation are also not reported.

Third, although the record lists 72 participants enrolled, it does not provide a complete account of endpoint-specific denominators or participant flow. The population definition for the primary endpoint is stated, but missing assessments, discontinuations, and analysis populations are not described. Fourth, safety summaries are limited to counts and selected serious-event terms. Event-level timing, attribution, severity details, overlap between categories, and the denominator for the listed term percentages are not reported in the registry record.

Fifth, secondary outcomes are named but their numerical results are not reported. The statistical analysis plan, multiplicity approach, missing-data methods, sample-size justification, and interim analyses are also not reported in the registry record. The cohort descriptions are partly abbreviated, so not every regimen detail can be recovered from the posted descriptions.

These gaps limit assessment of precision, completeness, and analytic decisions. They do not show that the study’s investigators did or did not perform a particular analysis; they mean that the relevant information is unavailable in this registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors — NCT02718911.
• Registry record last updated 2023-10-16; status last verified 2023-10.
• Results first posted 2023-10-16.
• 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

This completed phase 1 study evaluated LY3022855 with durvalumab or tremelimumab in participants with advanced solid tumors. It was non-randomized, unmasked, and sequential, with reported enrollment of 72. The primary endpoint concerned the recommended phase 2 dose of LY3022855 with durvalumab, based on DLT assessment and an MTD definition during Cycle 1 (4 weeks).

The registry provides cohort-level safety counts and lists response, disease control, antibody, and pharmacokinetic outcomes. It does not report the numerical primary endpoint result or numerical results for those secondary outcomes. Because there was no randomized control arm, the safety cohorts should be interpreted descriptively rather than as direct comparisons. The record also does not report key analysis details, including missing-data methods and the statistical analysis plan.