Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors (NCT03150810), a non-randomized phase 1 study. The primary outcome is Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

The registry record describes a completed, non-randomized Phase 1 study, with an official title identifying it as Phase 1b. Enrollment was 139. The study began on 2017-06-28, and primary completion was 2023-05-04. The design model is sequential, and masking was none. These features describe a dose-finding study rather than a randomized comparison of treatment against a control.

Participants received pamiparib with temozolomide. Dose escalation varied temozolomide dose and administration schedule while the pamiparib schedule was generally 60 mg twice daily. Escalation regimens included temozolomide on Days 1 to 7, Days 1 to 14, or continuously on Days 1 to 28 of a 28-day cycle. Expansion groups used temozolomide 60 mg on Days 1 to 7 with pamiparib 60 mg twice daily on Days 1 to 28. The expansion groups were organized by tumor type.

The primary objective included assessing safety and tolerability, determining the maximum tolerated dose or maximum administered dose, selecting a recommended Phase 2 dose and schedule, and determining antitumor activity. The listed primary endpoint is the number of participants with dose-limiting toxicities in dose escalation. The registry record does not report the rationale for the enrollment target, a formal dose-escalation algorithm, or a statistical analysis plan. Because there was no randomized control group, differences between dose or tumor groups should not be interpreted as controlled treatment effects.

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.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The dose-escalation safety analysis set comprised all dose-escalation phase participants who received pamiparib and/or TMZ.

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.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs), measured over From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months).

The primary endpoint counts participants with dose-limiting toxicities during the dose-limiting toxicity assessment window. The registry defines a dose-limiting toxicity as specified severe toxicities occurring from first dose through the assessment window. The listed criteria include grade 3 or higher non-hematologic, non-hepatic major organ adverse events; prolonged grade 4 neutropenia; grade 3 or higher febrile neutropenia; clinically significant bleeding with grade 3 thrombocytopenia; specified severe thrombocytopenia; grade 4 or higher anemia; and grade 3 or higher total bilirubin or hepatic transaminases.

The assessment window is described as running from first dose of study drug or drugs to 28 days post-dose, with the timeframe stated as up to approximately 1 year and 6 months. The endpoint is used in early-phase dose escalation because observing these predefined toxicities can inform evaluation of tolerability and dose selection. A participant count is not itself a complete account of severity, timing, or clinical context; those details require the relevant event-level information.

The registry record does not report the number of participants who experienced a dose-limiting toxicity. Consequently, the primary endpoint cannot be interpreted from the listed endpoint definition alone. The record also does not report a dose-limiting toxicity rate, uncertainty interval, or dose-level conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count convey? The primary endpoint is a count of participants meeting the dose-limiting toxicity definition. In general, a count is most interpretable alongside the number of participants assessed and a clear time window. A count alone does not express the frequency in a population or the uncertainty around that frequency. Here, the endpoint definition and assessment window are stated, but the endpoint result is not reported in the registry record. A rate, confidence interval, or formal comparison cannot be recovered from the endpoint definition.

Why is a defined toxicity window important? Dose-limiting toxicity criteria are applied within a stated assessment period so that events relevant to early dose evaluation can be counted consistently. The registry specifies the period as from first dose to 28 days post-dose, with the timeframe described as up to approximately 1 year and 6 months. In general, events outside an assessment window may not be counted toward that endpoint even if they are included in other safety reporting. The record does not describe further rules for adjudication, handling incomplete observation, or attributing an event to a treatment.

How should the dose groups be understood? The study is described as sequential and non-randomized. The dose-escalation groups used varying temozolomide doses and schedules, and expansion groups were organized by cancer type. In general, sequential dose-finding designs evaluate experience as dosing proceeds, rather than assigning all participants concurrently to randomized alternatives. The registry record does not report the specific escalation algorithm, decision boundaries, or rules for moving between dose groups. Without those details, the design can be described, but its decision process cannot be reconstructed.

What can adverse-event counts show? The safety listings give, for each group, the number at risk and the number affected by serious adverse events and other adverse events, as well as a death count. These are descriptive summaries. In general, a count should be interpreted with its denominator, event definition, observation period, and participant characteristics in mind. A group with a different number of participants or different follow-up may have a different count for reasons unrelated to a treatment effect. The non-randomized design does not remove these potential differences. The registry record does not provide enough information in the registry record to determine treatment attribution or to compare risks using an adjusted analysis.

What does a confidence interval mean? In general, a confidence interval expresses the uncertainty of an estimated quantity under a specified statistical method. It is not a guarantee that the true value lies in the interval, and its interpretation depends on the estimate, data, and method. No confidence interval for the primary endpoint is reported in the registry record, so uncertainty about the dose-limiting toxicity result cannot be quantified from the posted endpoint information.

What do the planning assumptions mean? The stated sample-size planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes an effect to detect as a stated fraction of the observed effect. These are planning assumptions for an illustration, not evidence that the trial was designed with those assumptions. The record specifically distinguishes the illustration from the trial's own design. The arms in this study are not a randomized, like-for-like comparison, so those hypothetical planning assumptions should not be read as a description of the actual allocation. Any sample sizes from such an illustration are planning quantities, not observed power.

What statistical plan is documented? The registry record lists no statistical analyses. The full analysis methods, including whether estimates were adjusted, how missing observations were handled, how multiplicity was addressed, and how dose selection was formally determined, are not reported in the registry record. General statistical principles can explain why these choices matter, but they cannot fill in the study-specific methods that are absent from the record.

Why does over-dispersion matter in general? For count outcomes, a simple model may assume that variability follows a particular probability structure. Over-dispersion means the observed variability is greater than that assumption allows; if ignored, uncertainty can be understated. This is a general consideration for count analyses, not a method reported for this study. The primary endpoint is a count of participants with an event, and the registry record does not report a model or analysis that would allow assessment of over-dispersion.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Dose Escalation: Pamiparib + Temozolomide (TMZ) 40", "Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)", "Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)", "Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)", "Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)", "Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)")
n      <- c(4, 13, 9, 3, 3, 14)
events <- c(0, 0, 0, 2, 2, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dose Escalation: Pamiparib + Temozolomide (TMZ) 40  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple additional outcomes, including pharmacokinetic measures such as maximum observed plasma concentration, trough concentration, time to maximum concentration, areas under the curve, terminal elimination half-life, apparent clearance, and apparent volume of distribution. It also states that the study objectives included antitumor activity. The statistical plan for these outcomes, including whether any formal hypothesis tests were planned, is not reported in the registry record.

Multiplicity arises when several outcomes, doses, groups, or comparisons are examined. In general, conducting many statistical tests can increase the chance of a seemingly notable result arising by chance. Study-specific interpretation depends on which outcomes were prespecified as primary or secondary, what testing hierarchy or adjustment was used, and how results were selected for reporting. Those details are not reported in the registry record, so no multiplicity adjustment or testing strategy can be attributed to this study.

The record lists no statistical analyses. It also does not report methods for missing data, incomplete follow-up, participants excluded from particular analyses, or sensitivity analyses. The primary endpoint population is described as the dose-escalation safety analysis set, comprising all dose-escalation participants who received pamiparib and/or temozolomide. That definition does not by itself explain how missing assessments or partial exposure were handled. The analysis population for the expansion groups is not stated in the registry record for interpretation.

These omissions matter because outcome estimates can depend on the analysis population and the treatment of missing observations. In general, analyses based on different participant sets can answer different questions. Without the study-specific methods and results, neither the effect of missing information nor the treatment of multiple outcomes can be evaluated.

12. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (33.3%), oesophagitis (33.3%), urinary tract infection (33.3%), spinal compression fracture (33.3%), acute kidney injury (33.3%).

The serious adverse-event listings give group-specific numbers at risk and numbers affected. For example, the dose-escalation group receiving temozolomide 60 mg on Days 1 to 7 had 4 of 13 participants listed as affected by serious adverse events; the gastric cancer expansion group had 9 of 21. These are descriptive counts for their respective groups, not controlled comparisons. The treatment groups differ in regimen, tumor population, and size, and the study was not randomized.

The listings also report other adverse events and deaths by group. These entries should not be assumed to establish treatment causation. The registry record does not state that the listed deaths were caused by study treatment, and the safety counts do not establish whether a particular event met the primary dose-limiting toxicity criteria. Serious adverse events, other adverse events, deaths, and dose-limiting toxicities are distinct reporting categories.

The registry lists Abdominal pain, Oesophagitis, Urinary tract infection, Spinal compression fracture, Acute kidney injury, and Haematuria among the top serious terms, each at 33.3%. The denominator and event-count context for those term percentages are not reported in the registry record. They should not be interpreted as percentages of all enrolled participants or compared across groups without that context.

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

The record describes an early-phase, non-randomized study of pamiparib combined with temozolomide. It documents dose-escalation regimens, tumor-specific expansion groups, the dose-limiting toxicity definition, and group-level safety counts. The record also identifies safety, tolerability, dose selection, and antitumor activity as study objectives. These descriptions establish what the trial set out to examine, but they do not provide the primary endpoint result.

The reported adverse-event counts can be read as observations among participants in the listed groups. They do not establish comparative safety because there was no randomized control group and the groups were not like-for-like. They also do not establish that an event or death was caused by study treatment. Interpretation of the listed serious-event percentages is constrained because their denominator and event-count context are not reported in the registry record.

The registry record does not report the number of participants with dose-limiting toxicities, the estimated antitumor activity, or a recommended Phase 2 dose conclusion. It also does not provide inferential analyses or confidence intervals for these results. Accordingly, the posted information cannot establish the frequency or precision of the primary endpoint, compare treatment effects, or show whether the combination had antitumor activity.

More generally, an early-phase dose-escalation study and a randomized efficacy study answer different questions. Dose-finding can describe experience across regimens and help inform further evaluation, while a controlled comparison is designed to estimate differences between assigned treatments. The registry record supports the former design description; it does not supply results sufficient to draw conclusions about comparative benefit or harm.

14. Why This Trial Matters Statistically

This study illustrates why an early-phase trial should be interpreted through its design and endpoint, not only through its treatment-group labels. Its sequential, non-randomized structure and varying doses and schedules are relevant to dose exploration. They do not create a randomized control comparison. Tumor-specific expansion groups also represent different clinical populations, so their counts should be read separately rather than treated as interchangeable arms.

The distinction between the primary dose-limiting toxicity endpoint and broader adverse-event reporting is statistically important. The endpoint uses a defined set of toxicity criteria and an assessment window; serious adverse events and other adverse events are separate registry summaries. One category cannot serve as a substitute for another. When the primary result itself is absent, detailed safety counts still do not answer the registered primary endpoint question.

The record also shows why completeness of statistical reporting matters. The objectives include dose selection and antitumor activity, yet the primary endpoint result and analysis methods are not reported in the registry information available for interpretation. Without those results, readers cannot assess the uncertainty around dose-limiting toxicity or the evidence underlying a dose-selection conclusion. Missing details on analysis populations, missing observations, and multiplicity further limit evaluation of the reported objectives.

For biostatisticians and clinical researchers, the practical lesson is to separate design description, descriptive safety reporting, and inferential evidence. A registry can document important features of a trial while leaving essential results and methods unavailable. Each claim should be kept within the scope of what is actually reported.

15. 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 that the registry record does not report the result for the stated primary endpoint, the number of participants with dose-limiting toxicities. The record therefore does not support estimating the observed endpoint frequency or its uncertainty. Although adverse-event counts are listed, they are distinct from the dose-limiting toxicity endpoint and cannot fill this gap.

The study is non-randomized, unmasked, and sequential, and it has no like-for-like control comparison. Regimens vary across dose-escalation groups, while expansion groups represent different tumor types. The group-level adverse-event counts should not be interpreted as controlled differences in risk. The record does not provide adjusted comparisons or enough information to evaluate treatment attribution for events and deaths.

Statistical methods for dose escalation, dose selection, missing observations, multiplicity, and inferential analysis are not reported in the registry record. The record lists no statistical analyses. It also does not report results for the antitumor activity objective or a recommended Phase 2 dose conclusion. For the top serious adverse-event terms, the denominator and event-count context behind the reported percentages are not stated in the registry record for interpretation.

These limitations concern the available registry information; they do not establish what analyses may have been conducted elsewhere. The record supports description of the trial design and listed safety counts, but not conclusions beyond those reported quantities.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors — NCT03150810.
• Registry record last updated 2024-12-20; status last verified 2024-12.
• Results first posted 2024-12-20.
• 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.

19. Record Summary

This completed, non-randomized Phase 1 study enrolled 139 participants with locally advanced or metastatic solid tumors. The official title describes a Phase 1b study. Pamiparib was combined with temozolomide in sequential dose escalation and tumor-specific expansion groups. The primary endpoint was the number of dose-escalation participants with dose-limiting toxicities during the stated assessment window.

The registry lists group-specific adverse-event and death counts, but does not report the primary endpoint result, antitumor activity results, a dose-selection conclusion, or statistical analyses. The methods for missing data and multiplicity are not reported in the registry record. Because allocation was non-randomized and there was no control comparison, the group counts are descriptive rather than evidence of comparative treatment effects.