Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer (NCT02981303), a non-randomized phase 2 study. The primary outcome is The Primary Efficacy Endpoint Was ORR, Defined as the Proportion of Subjects Demonstrating CR or PR Based on RECIST v1.1 Criteria..

2. Clinical Question

The study’s stated hypothesis was that Imprime PGG might restore sensitivity to checkpoint inhibitors in melanoma or enhance it in TNBC after front-line treatment failure. That is the rationale being tested, not an established effect. The registry identifies overall response rate (ORR) as the primary efficacy endpoint and describes safety characterization as an objective. It does not report numerical response results, so the main efficacy question cannot be answered from the registry record.

3. Trial Design

This was a multicenter, open-label, Phase 2 study with non-randomized allocation and parallel tumor-type cohorts. The registry records 64 participants enrolled. Participants with advanced melanoma and participants with TNBC received the same combination, Imprime PGG plus pembrolizumab. Because treatment assignment was not randomized and there was no control arm, the study does not provide a randomized estimate of the combination’s effect relative to another treatment or to no combination treatment.

The brief study description specifies a Simon optimal two-stage approach, with Stage 1 planned for 12 participants in each tumor type. The description set a Cycle 1 safety threshold: at most 4 (or 33%) participants with Grade 3/4 adverse events in either tumor type to proceed at that dose. If more than 4 (or 33%) had such events, it describes reducing Imprime PGG from 4 mg/kg to 2 mg/kg and repeating Stage 1 with an additional cohort of 12. It also describes a minimum response requirement in Stage 1 to proceed: at least 1 response among melanoma participants and 2 among TNBC participants. Stage 2 was described as an additional 17 participants with melanoma and 30 with TNBC. The available study summary ends before the full Stage 2 success rule is stated, so that rule is not reported in the registry record.

The registry records the study as completed, with a start date of 2017-02-22 and primary completion on 2020-12-31. These design details describe the planned conduct; without reported response outcomes and analysis details, they do not establish whether the planned decision criteria were met.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects screened for the study who received at least one dose of study drug (primary population for baseline characteristics and safety analyses and secondary population for efficacy analyses).

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 screened for the study who received at least one dose of study drug (primary population for baseline characteristics and safety analyses and secondary population for efficacy analyses).

6. Primary Endpoint

The registry lists the primary outcome as The Primary Efficacy Endpoint Was ORR, Defined as the Proportion of Subjects Demonstrating CR or PR Based on RECIST v1.1 Criteria., measured over From the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier, up to 24 months..

The primary efficacy endpoint was ORR, defined as the proportion of participants whose best response was complete response (CR) or partial response (PR) under RECIST v1.1. Tumor response criteria provide a standardized way to classify changes in measurable disease. ORR condenses those classifications into the share of participants who achieved either of the specified response categories. It does not, by itself, describe how long a response lasted, whether disease control was durable, or how participants fared on survival outcomes.

The registry says best response was assessed from the start of study treatment until the first progressive disease (PD) under RECIST v1.1 or the start of a new cancer therapy, whichever occurred earlier. Response assessment was scheduled every 6 weeks after the first dose. The listed timeframe extends up to 24 months. Thus, the endpoint depends on response observations over a defined treatment and follow-up period, as well as on the registry’s stated stopping rules for the response window.

ORR is commonly used in early-phase oncology studies because it records whether a participant’s disease met predefined response criteria during treatment. General statistical interpretation: a response proportion is a descriptive estimate for the participants analyzed; its precision depends on the number of participants and the number with response. The registry record does not report the CR count, PR count, ORR estimate, or confidence interval. Therefore, the endpoint’s definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: clinical trial design determines what conclusions can be drawn from observed outcomes. Random assignment can make treatment groups more comparable on average, while a non-randomized study can describe outcomes in the enrolled groups but is more vulnerable to differences between participants and other sources of bias. This study is recorded as non-randomized, open-label, and parallel. Both tumor-type cohorts received Imprime PGG plus pembrolizumab, and there was no randomized control group. The design therefore does not estimate a treatment contrast against a concurrent randomized comparator.

What does the two-stage plan mean?

The study summary describes a Simon optimal two-stage design separately for melanoma and TNBC. General: a two-stage design can use an initial cohort to assess whether a treatment appears promising enough, and sufficiently safe under specified rules, to justify enrolling a later cohort. The design may limit further enrollment if predefined criteria are not met. Here, the registry summary specifies 12 participants in Stage 1 for each tumor type, safety criteria based on Grade 3/4 adverse events during Cycle 1, and minimum response counts required to proceed. It also describes a possible reduction in Imprime PGG dose and a repeat Stage 1 cohort if the safety threshold was exceeded. The planned Stage 2 additions are 17 participants with melanoma and 30 with TNBC.

Those are planned rules, not evidence that the rules were applied as described or that a stage was passed. The registry record does not report the stage-specific enrollment and outcomes, the dose actually received by each cohort, or whether the response and safety thresholds were satisfied. The available summary also ends before the full Stage 2 success rule, so that rule is not reported in the registry record.

How should ORR be understood?

The primary endpoint counts participants whose best response was CR or PR under RECIST v1.1. General: the response proportion is a binary outcome at the participant level: each participant either meets the response definition or does not. This makes the endpoint straightforward to describe, but a proportion alone does not show response duration, progression-free survival, overall survival, or the treatment’s effect relative to a control. The registry lists time to response, complete response rate, duration of overall response, progression-free survival, and overall survival among secondary outcomes. Their definitions or numerical results are not reported in the available record.

The registry describes response assessment every 6 weeks after the first dose and a response window ending at the first PD or start of new cancer therapy, whichever occurred earlier, up to 24 months. General: the timing and rules for assessment matter because an endpoint depends on when measurements are made and how follow-up ends. The record does not describe independent central review, missing-scan handling, or additional rules for confirmation of response; these details are not reported in the registry record.

What does statistical precision mean?

General: a confidence interval represents the uncertainty around an estimated effect or proportion under the statistical model used. A narrower interval indicates greater precision, while a wider interval indicates less precision. The registry record does not report an ORR confidence interval, so readers cannot assess the precision of an observed response estimate from this record. It also lists zero analyses, and no primary efficacy p-value or inferential analysis is reported.

The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. General: such calculations depend on their assumptions and are planning illustrations rather than observed trial findings. They are not observed power, and they cannot replace a reported effect estimate with its uncertainty. The study itself is non-randomized and does not have two treatment arms in a like-for-like control comparison, so any two-arm planning illustration should not be mistaken for the trial’s design or an estimate of comparative efficacy. The registry record does not report the trial’s own sample-size justification.

How do safety counts differ from efficacy estimates?

Safety summaries count participants with specified adverse events among those at risk for the relevant summary. The registry records serious adverse events in 3 of 20 melanoma participants and 9 of 44 TNBC participants. These counts do not describe the primary response endpoint. General: adverse-event counts can also depend on definitions, observation time, and whether events are counted by participant or by event; the record’s exact conventions beyond the displayed group counts are not reported in the registry record. Safety counts are descriptive and do not establish causation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary efficacy endpoint, ORR, and several secondary outcomes: time to response, complete response rate, duration of overall response, progression-free survival, and overall survival. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan. These details are not reported in the registry record. General: when several outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiple testing. Without a stated approach, the strength of any collection of outcome claims cannot be assessed from the registry record.

Missing-data methods are not reported in the registry record. The endpoint description gives a response-assessment schedule and a stopping rule based on PD or new cancer therapy, but it does not state how unevaluable participants, missed assessments, or withdrawal from follow-up were handled in the primary efficacy analysis. The record’s population description says participants were screened and received at least one dose; it characterizes this population as primary for baseline and safety analyses and secondary for efficacy analyses. A separate, clearly described efficacy analysis population and its handling of participants with incomplete response assessments are not reported.

The registry lists zero analyses and does not report an ORR estimate, confidence interval, or p-value. This does not establish that no analyses were conducted; it means analyses and results are not reported in the registry record. Without those details, readers cannot evaluate the prespecified testing approach, missing-data assumptions, or the relationship between the planned design and the reported efficacy analysis.

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: femur fracture (5.0%), infusion related reactions (5.0%), pulmonary embolism (5.0%), hypotension (5.0%), haemorrhage intracranial (5.0%).

The registry records serious adverse events for 3 of 20 participants with melanoma and 9 of 44 participants with TNBC. It lists deaths for 1 participant in the melanoma group and 2 participants in the TNBC group. The record does not state whether these deaths were caused by an adverse event or related to study treatment. The figures should therefore be read as counts in the registry’s safety summary, not as causal treatment effects.

The registry also lists serious adverse event terms with percentages: Femur Fracture, Infusion Related Reactions, Pulmonary Embolism, Hypotension, and Haemorrhage intracranial are each listed as 5.0%; Pancreatitis is listed as 4.5%. The record does not provide the event-specific participant counts alongside these percentages or explain their denominator in the available information. It is therefore not appropriate to infer a count or compare the percentages across tumor types from these entries alone.

General: serious adverse event summaries are useful for describing events that meet seriousness criteria, but they do not by themselves show whether treatment caused an event. Interpretation also depends on the definition, follow-up period, and attribution process. Those details are not reported in the registry record. The listed other adverse events affect 20 of 20 melanoma participants and 44 of 44 TNBC participants in the recorded safety groups; the registry does not provide further detail about event severity or attribution.

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

The study was designed to examine ORR and safety for Imprime PGG plus pembrolizumab in participants with advanced melanoma or metastatic TNBC after specified front-line treatment failure. The registry describes the endpoint definition, response-assessment schedule, planned staged design, and safety counts. It does not report numerical primary efficacy results. As a result, the posted information cannot establish the observed ORR, its precision, or whether the response thresholds in the study plan were met.

This distinction is not a conclusion that the combination had no responses or that it was ineffective. The registry record does not report the response data needed to make those judgments. Similarly, the presence of serious adverse events or deaths in the safety summaries does not establish that study treatment caused them. The record does not state the relationship of the listed deaths to treatment.

Even if the response results were available, the non-randomized design and lack of a control group would limit comparative interpretation. Responses among treated participants would be observed outcomes in these cohorts; they would not on their own show what would have happened under another treatment. The melanoma and TNBC groups also represent distinct clinical populations, so their outcomes should not be treated as a direct comparison of treatment efficacy.

General: an early-phase study can provide descriptive information about response and safety and can use prespecified progression rules to guide further study. It does not automatically establish comparative benefit or resolve uncertainty about outcomes in other populations. For this record, the planned questions are clear, but the absence of posted efficacy estimates and analysis details leaves the primary statistical result unresolved.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of an early-phase, non-randomized study organized around separate tumor-type cohorts and a planned two-stage decision process. The design summary distinguishes safety monitoring from efficacy screening: continuation was to depend on Cycle 1 adverse-event criteria as well as minimum response counts. Such rules make the decision structure explicit in the protocol description, but interpretation still requires the stage-specific outcomes and the final success rule.

The registry also illustrates why an endpoint definition is not a result. ORR is clearly defined as CR or PR by RECIST v1.1, with regular response assessment and a stated observation window. Yet no response counts or ORR estimates are reported. Without those values and their uncertainty, readers cannot evaluate whether the planned efficacy question was answered.

The non-randomized structure is important to statistical interpretation. Both disease cohorts received the combination, so there is no randomized treatment contrast. Descriptive response or safety summaries, when posted, would characterize outcomes in these enrolled groups but would not by themselves quantify the effect of the combination compared with a control.

Finally, the record underscores the role of complete reporting. Stage-specific enrollment, dose allocation, missing-data methods, analysis populations, multiplicity handling, and efficacy estimates would all help readers connect the study plan to its results. These details are not reported in the registry record. The study’s design can be described, but the missing outcome and analysis information prevents a full statistical assessment of its primary objective.

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 most important limitation for interpreting the primary endpoint is that the registry record does not report numerical ORR results. There are no CR or PR counts, cohort-specific response estimates, confidence intervals, or efficacy p-values in the available record. As a result, the primary efficacy question remains unanswered by the posted results.

The study is non-randomized and does not include a like-for-like control group. Any observed outcomes would therefore be difficult to separate from differences in participant characteristics, disease type, prior treatment, or other factors. The melanoma and TNBC cohorts are different populations and should not be interpreted as randomized alternatives to one another.

The design description outlines planned stage criteria, but actual stage-by-stage enrollment, dose use, and whether the criteria were met are not reported in the registry record. The brief summary does not give the complete Stage 2 success rule. The registry also does not report the trial’s own sample-size justification, a statistical analysis plan, multiplicity procedures, or methods for missing and unevaluable response assessments.

Safety figures are limited to the recorded counts and listed terms. The available record does not give event attribution, detailed follow-up context, or the denominator used for the listed serious-event term percentages. The deaths are not described as treatment-related or unrelated. These omissions limit causal and comparative interpretation of the safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer — NCT02981303.
• Registry record last updated 2024-07-09; status last verified 2024-06.
• Results first posted 2024-07-09.
• 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.

18. Record Summary

NCT02981303 is a completed, multicenter, open-label, non-randomized Phase 2 study of Imprime PGG plus pembrolizumab in advanced melanoma and TNBC. The registry records 64 participants enrolled. Its primary efficacy endpoint was ORR, defined by CR or PR under RECIST v1.1, with response assessments every 6 weeks after the first dose and a stated timeframe up to 24 months. The study summary describes a Simon two-stage plan with safety and response criteria.

The registry records serious adverse events in 3 of 20 melanoma participants and 9 of 44 TNBC participants, and deaths in 1 and 2 participants, respectively. It does not report numerical ORR results, efficacy analyses, or the treatment relationship of deaths. Stage-specific outcomes and several statistical analysis details are not reported in the registry record.