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 Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer (NCT02963610), a na phase 1, phase 2 study. The primary outcome is To Determine the Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With a Fixed Dose of Pembrolizumab in Subjects With Relapsed and/or Refractory Solid Tumors..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02963610 |
| Phase | Phase 1, Phase 2 |
| Condition | Relapsed or Refractory Solid Tumors, Nonsmall Cell Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Fox Chase Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The planned phase I population was people with histologically confirmed advanced, relapsed or refractory solid tumors. The planned phase II population was people with histologically confirmed non-small cell lung cancer, regardless of histologic subtype, who had completed one line of standard therapy. The registry record reports enrollment of 3, but does not report participant-level characteristics or which planned component or population those participants represented.
Intervention
The study investigated lenalidomide in combination with pembrolizumab. The phase I description says pembrolizumab would be given at a fixed dose while the lenalidomide dose escalated by cohort. The registry record describes the study as single-group and unmasked. It does not report analyses of treatment exposure or clinical outcomes.
Comparator
There was no separate comparator group in the registry design. Allocation is recorded as not applicable, and the model is single-group. The regimen therefore was not compared within this trial against pembrolizumab alone, lenalidomide alone, or another treatment. Any outcome description cannot establish a comparative treatment effect.
Primary question
The posted primary endpoint asks what maximum tolerated dose of lenalidomide can be used with a fixed dose of pembrolizumab in people with relapsed or refractory solid tumors. Its stated assessment time is Day 22 of cycle 1. The summary also describes a planned phase II question about progression-free survival in non-small cell lung cancer, but the posted primary outcome is the phase I dose question. The record says the study ended early because grantor funding or support was withdrawn and that no analyses occurred; consequently, it supplies no answer to either clinical question.
3. Trial Design
The registry describes a phase I/II, open-label, single-group study of lenalidomide plus pembrolizumab. It records allocation as not applicable and masking as none. These features mean there was no randomized assignment or blinded treatment comparison described in the record. The study was sponsored by Fox Chase Cancer Center.
The phase I component was planned to use a classic 3 + 3 dose-escalation design. Pembrolizumab was to remain at a fixed dose while lenalidomide doses changed across cohorts; the stated purpose was to determine the maximum tolerated lenalidomide dose in combination. The registry summary describes a 21-day treatment cycle and gives a fixed pembrolizumab dose of 200 mg. The available arm description is incomplete, so further dose-cohort details are not reported in the registry record.
The phase II component was planned as a two-stage design in non-small cell lung cancer. The summary states that it would initially enroll 13 patients, followed by 13 more if early stopping criteria were not met. Its planned primary endpoint was progression-free survival. The actual stopping criteria and the detailed statistical procedures for either component are not reported in the registry record.
The study started on 2017-03-29, had a primary completion date of 2017-10-03, and is recorded as terminated. Enrollment was 3. The registry attributes premature termination to funding or support being withdrawn by the grantor and explicitly states that no analyses occurred. Thus the planned design should not be confused with a completed evaluation: the stated dose-escalation and phase II plans do not amount to evidence that either endpoint was analyzed.
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
| Stage | Pembrolizumab, Lenalidomide |
|---|---|
| STARTED | 3 |
| COMPLETED | 0 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Pembrolizumab, Lenalidomide |
|---|---|
| Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | 3 |
Analysis population for the primary outcome, as defined in the registry: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred
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.
| Characteristic | Unit | Pembrolizumab, Lenalidomide |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 1 |
| Race/Ethnicity, Customized: White Non-Hispanic | Participants | 2 |
| Race/Ethnicity, Customized: Black or African American | Participants | 1 |
| Region of Enrollment: United States | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as To Determine the Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With a Fixed Dose of Pembrolizumab in Subjects With Relapsed and/or Refractory Solid Tumors., measured over Day 22 of cycle 1.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The posted primary endpoint is the maximum tolerated dose of lenalidomide combined with a fixed dose of pembrolizumab, with assessment at Day 22 of cycle 1. In a dose-escalation study, this endpoint is intended to identify a dose level whose observed tolerability meets a protocol-defined rule. It is a safety and dose-selection question, not a direct measure of tumor response or progression-free survival. The exact toxicity definitions, assessment rules, and dose-limiting toxicity window beyond the stated timeframe are not reported in the registry record.
The registry summary separately describes progression-free survival as the planned primary endpoint for the phase II component. In general, progression-free survival measures time until a defined disease-progression event or death, but the endpoint definition and assessment procedures specific to this study are not reported in the registry record. The phase I primary outcome and the phase II plan address different questions and populations. The primary outcome record identifies the phase I maximum tolerated dose question, while the summary describes a future phase II efficacy assessment. Neither result is reported: the registry says the trial was terminated prematurely and no analyses occurred.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the trial has no reported analysis. Although the record lists enrollment of 3 and includes adverse-event counts, it states that the study was terminated prematurely after funding or support was withdrawn and that no analyses occurred. There is therefore no posted estimate of the maximum tolerated dose, no progression-free survival result, and no objective response result. A planned outcome is not an observed outcome, and a registered design is not evidence that its analysis was completed.
The design also limits what could be learned even if descriptive outcomes had been reported. This was a single-group study without a comparator. A single-group observation can describe what happened among enrolled participants, but it cannot distinguish the effect of the combination from the natural course of disease, other care, or other influences. It cannot establish comparative benefit or harm against another regimen. This is especially important when interpreting secondary outcomes such as objective response rate, which is listed as an intended assessment rather than a posted analysis.
For the phase I question, a maximum tolerated dose is ordinarily determined through a prespecified dose-escalation rule linked to toxicity observations. The registry gives the broad design label, but does not report the actual dose assignments, toxicity-based decisions, or a selected dose. Without those elements and an analysis, the endpoint cannot be reconstructed from the record. The phase II progression-free survival plan is also not accompanied by event counts, follow-up summaries, or a survival estimate. The record does not report a confidence interval or other measure of precision for either primary question.
The safety record lists 3 participants at risk for serious adverse events and 0 with serious adverse events; it also lists 3 at risk for other adverse events and 3 with other adverse events, along with 2 deaths. These counts should be read as registry safety entries, not as a treatment comparison or proof of causation. The record does not state whether the deaths were considered treatment-related, their timing, or their relationship to the adverse-event categories. Small enrollment and absent analysis make these figures limited descriptions rather than stable estimates of risk.
Overall, the registry documents a planned early-phase investigation and its termination, not a completed test of efficacy. The observed registry information does not support a treatment-effect estimate, a dose recommendation, or an inference that an outcome was caused by the study regimen. Additional outcome definitions, analytic methods, participant details, and reasons for the absence of analyses beyond the funding or support withdrawal are not reported in the registry record.
9. Statistical Methods Explained
The registry outlines two intended statistical stages, but does not report completed analyses. The concepts below explain the design labels generally; they do not describe analyses known to have been carried out in this trial.
How does a 3 + 3 dose-escalation design work?
In general, a 3 + 3 design assigns small cohorts of participants to successive dose levels and uses observed toxicities to guide whether escalation, expansion at a dose, or stopping is appropriate. The design is a structured way to make early dose decisions while limiting exposure to doses that appear poorly tolerated. Its result depends on the protocol's definitions of dose-limiting toxicity, assessment window, and escalation rules. The registry identifies a classic 3 + 3 plan and states that the phase I purpose was to determine the maximum tolerated dose of lenalidomide with fixed-dose pembrolizumab. The exact decision rules and toxicity definitions are not reported in the registry record. Because the registry says no analyses occurred, there is no reported dose decision to interpret.
What does a maximum tolerated dose represent?
In general, a maximum tolerated dose is a dose selected under defined rules based on the frequency or pattern of unacceptable toxicities during a specified period. It is a protocol-dependent dose-finding outcome, not a universal property of a drug combination. It should be interpreted together with the dose levels tested, observation period, toxicity definition, and number of participants assessed at each level. The registry gives Day 22 of cycle 1 as the primary outcome timeframe, but does not report toxicity definitions, cohort-level data, or the actual dose selected. No conclusion about a maximum tolerated dose can therefore be drawn from the record.
What is a two-stage design intended to do?
In general, a two-stage design allows an early look at accumulating data before proceeding to a further planned stage. Depending on its prespecified rules, such a design may stop early when results meet a stopping criterion, or continue enrollment when they do not. The registry summary says the phase II component was intended to begin with 13 patients and enroll 13 more if early stopping criteria were not met. It does not report the precise criteria, the statistical boundaries, or whether the planned stages were reached. The enrollment and termination information cannot by itself establish that the early stopping rule was applied; the record attributes termination to grantor funding or support being withdrawn and says no analyses occurred.
How should progression-free survival be understood?
In general, progression-free survival is a time-to-event endpoint. It requires a definition of the event, a method for establishing when it occurred, and rules for handling participants whose event is not observed during follow-up. The phase II summary names progression-free survival as the planned primary endpoint, but the primary outcome entry concerns the phase I maximum tolerated dose. The registry does not report the phase II event definition, assessment schedule, censoring rules, follow-up duration, event count, or survival analysis. Without those details and an analysis, there is no progression-free survival estimate to interpret.
What would a confidence interval add?
In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision under those assumptions, while a wider interval indicates less precision. It does not remove bias, create a comparison that the design did not include, or prove that an effect is causal. No estimate or confidence interval for the primary outcomes is reported in the registry record. Consequently, there is no precision interval on which to base an inference about dose, progression-free survival, or treatment effect.
Why does the single-group design matter?
In general, a single-group trial can describe outcomes in participants receiving the studied regimen, but it lacks a concurrent control group for separating regimen-related differences from other explanations. Randomization, when used, helps make treatment groups comparable on average; this registry record instead describes a single-group design with allocation marked not applicable. There is no like-for-like control comparison. Thus even a reported response or survival result would need to be interpreted as an outcome in the enrolled group rather than a measured advantage over another treatment. In this record, no efficacy analyses are reported at all.
Taken together, the design descriptions explain how the investigators planned to approach dose finding and a later disease-outcome question. They do not supply evidence that the rules were applied or that either endpoint was estimated. The registry record's explicit statement that no analyses occurred takes precedence over assumptions that might otherwise be made from the design labels.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several planned secondary assessments, including objective response rate, PD-L1 expression, blood immune-cell proportions, cytokine profiles, natural killer cell responses, immune-cell activation markers, tumor immune composition, and response among participants previously treated with an anti-PD1 antibody. These are distinct questions and involve different types of measurements. When many outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or any completed tests. Since it states that no analyses occurred, there are no reported secondary findings to weigh or adjust.
Missing-data handling is also not reported in the registry record. It does not describe how incomplete outcome assessments, missed visits, or loss to follow-up would be handled for the planned endpoints. The phase II time-to-event plan would generally require rules for incomplete follow-up and censoring, but the study-specific rules are not reported. The record does not provide analysis populations, such as which participants would be included in a dose-limiting toxicity or progression-free survival analysis. Enrollment of 3 is reported, but this does not establish the population used for any endpoint analysis, particularly when the record explicitly says no analyses occurred.
Accordingly, statistical adjustment, missing-data assumptions, and analysis-population choices cannot be evaluated from the registry record. They should not be inferred from the two-stage or 3 + 3 design descriptions.
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 |
|---|---|---|---|
| Pembrolizumab, Lenalidomide | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pembrolizumab, Lenalidomide | 2 of 3 |
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 |
|---|---|
| Pembrolizumab, Lenalidomide | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pembrolizumab, Lenalidomide |
|---|---|---|
| Constipation | Gastrointestinal disorders | 2 of 3 |
| Abdominal distension | Gastrointestinal disorders | 2 of 3 |
| Pruritis | Skin and subcutaneous tissue disorders | 2 of 3 |
| Diarrhea | Gastrointestinal disorders | 1 of 3 |
| Fecal incontinence | Gastrointestinal disorders | 1 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 3 |
| Anorexia | Metabolism and nutrition disorders | 1 of 3 |
| Hypoalkemia | Metabolism and nutrition disorders | 1 of 3 |
| Hyponatremia | Metabolism and nutrition disorders | 1 of 3 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 3 |
The registry safety entries list the Pembrolizumab, Lenalidomide group with 3 participants at risk for serious adverse events and 0 affected by serious adverse events. For other adverse events, the record lists 3 at risk and 3 affected. It also lists 2 deaths. These are counts in the registry record, not comparative rates: the study has no separate control group, and no rate calculation or treatment comparison is reported.
The counts do not establish whether an adverse event was caused by the regimen. The record does not report the timing, event descriptions, severity details, or relationship assessments for the deaths. It also does not provide an explanation for how the deaths relate to the serious and other adverse-event categories. The absence of a reported serious adverse event in this small enrolled group should not be interpreted as evidence that serious events cannot occur. Conversely, the count of other adverse events does not by itself show that the regimen caused them. The registry's statement that no analyses occurred is relevant: these entries are safety counts, not a completed statistical assessment of comparative safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase I/II study of lenalidomide plus pembrolizumab was registered, that enrollment was 3, and that the study was terminated. Its summary attributes premature termination to withdrawal of funding or support by the grantor. It also states that no analyses occurred. These registry entries describe the status and intended aims of the investigation; they do not show whether the combination met a dose-finding criterion or produced a particular clinical outcome.
The phase I aim was to determine the maximum tolerated lenalidomide dose with fixed-dose pembrolizumab. The phase II plan concerned progression-free survival in non-small cell lung cancer. Neither outcome is reported as an analyzed result. The registry also lists secondary immune and tumor activity assessments, but no findings from those assessments are posted. Therefore, no estimate of efficacy, dose, or outcome precision can be drawn from this record.
The single-group design further limits interpretation. Without a control group, the trial could not directly estimate how outcomes differed from another treatment in a like-for-like comparison. The safety counts also do not provide a causal comparison, and the registry does not describe whether the deaths were attributed to treatment.
These limitations do not erase the fact that a clinical study was planned and enrolled participants. They define what the registry record can support: a description of the design, enrollment, termination, and recorded safety counts. It cannot establish that the combination was effective or ineffective, that a particular dose was tolerable, or that the regimen caused the listed outcomes. More detailed participant information, endpoint results, and analyses are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its intended design and its available results are not the same thing. The record describes a phase I dose-escalation approach and a planned phase II expansion, but also states that termination occurred before analyses and that no analyses occurred. Readers must distinguish planned methods from completed statistical evidence. The presence of a detailed study aim does not mean the endpoint was measured or estimated.
The study also illustrates why endpoint alignment matters. The posted primary outcome is the phase I maximum tolerated dose, while the registry summary describes progression-free survival as the planned primary endpoint for the phase II component. Those endpoints answer different questions and apply to different planned populations. Treating them as one result would blur dose safety with disease outcome. Neither is reported as an analyzed result.
Its single-group design is another important statistical feature. Without a comparator, the design cannot estimate a relative treatment effect against another regimen. Even if an outcome had been reported, interpretation would need to account for the absence of a control group. Here, the record adds a more basic constraint: there are no posted analyses from which to estimate an outcome or its precision.
Finally, the registry shows why safety counts require context. Serious and other adverse-event entries and deaths are reported, but the causal relationship, timing, and analysis details are not. Counts alone cannot replace a structured comparison or a complete safety analysis. Together, these features make the study a useful example of the distinction between a registered clinical question, a planned statistical method, and an answer supported by analyzed data.
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 principal limitation is the absence of analyses. The registry explicitly states that the study ended prematurely because grantor funding or support was withdrawn and that no analyses occurred. There is no reported primary-endpoint result, no confidence interval, and no progression-free survival estimate. The stated enrollment of 3 does not indicate how many participants contributed to any specific endpoint or dose cohort.
The record gives only a broad description of the phase I 3 + 3 design and the phase II two-stage plan. Dose levels and escalation decisions are not fully described in the available arm text. Toxicity definitions, stopping rules, statistical boundaries, and specific analysis methods are not reported in the registry record. Consequently, planned methods cannot be audited against actual implementation.
The single-group design has no comparator and therefore cannot provide a within-trial comparative treatment effect. The registry also lacks detailed participant characteristics, treatment exposure, follow-up, endpoint event definitions, and missing-data procedures. The reported adverse-event counts are not accompanied by event-level detail or a stated causal assessment. Although 2 deaths are listed, their timing and relationship to treatment are not reported in the registry record.
These limitations mean that the posted information supports description of the registered plan, enrollment, termination, and safety counts only. It does not support estimates of efficacy, tolerability at a selected dose, or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer — NCT02963610.
- Registry record last updated 2021-12-30; status last verified 2021-12.
- Results first posted 2021-12-30.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a phase I/II, single-group, unmasked study of lenalidomide plus pembrolizumab in relapsed or refractory solid tumors, with a planned phase II expansion in non-small cell lung cancer. The phase I aim was to determine the maximum tolerated lenalidomide dose with fixed-dose pembrolizumab; the summary describes progression-free survival as the phase II aim. Enrollment was 3. The study started on 2017-03-29, had a primary completion date of 2017-10-03, and is recorded as terminated after grantor funding or support was withdrawn. The registry states that no analyses occurred. It lists 0 serious adverse events among 3 at risk, 3 other adverse events among 3 at risk, and 2 deaths. No analyzed primary or secondary outcome results are reported in the registry record.