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 A Study of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Participants With Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Rituximab in Combination With Idasanutlin and Venetoclax in Participants With R/R Diffuse Large B-Cell Lymphoma (DLBCL) (NCT03135262), a non-randomized phase 1, phase 2 study. The primary outcome is RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03135262 |
| Phase | Phase 1, Phase 2 |
| Condition | Follicular Lymphoma, Lymphoma, Large B-Cell, Diffuse |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants had relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study enrolled 29 participants across its dose-escalation cohorts. The record describes the study as multicenter and open-label.
Intervention
The study evaluated idasanutlin and venetoclax in combination with an antibody. Obinutuzumab was used in the FL cohorts; the DLBCL plan included obinutuzumab or rituximab during dose escalation and rituximab in the expansion cohort. The study planned to identify recommended phase II doses (RP2Ds) and a regimen.
Comparator
There was no randomized control group. This was a non-randomized, parallel-group, open-label dose-escalation study, so cohort outcomes are not a like-for-like comparison of assigned treatments. Differences between cohorts cannot be attributed to a treatment difference from these data alone.
Primary question
The primary measure was the RP2D of idasanutlin when given with obinutuzumab or rituximab, expressed in mg. The question was whether escalation would identify a dose for use in a planned expansion phase. The expansion phase did not take place, and no RP2D was identified in Cohorts 1 and 3.
3. Trial Design
This was a Phase Ib/II, open-label, multicenter, non-randomized, dose-escalation study in relapsed or refractory FL and DLBCL. Its planned sequence was dose escalation followed by expansion. The escalation phase was intended to identify recommended phase II doses and regimens for idasanutlin and venetoclax combined with an antibody. The study record says the expansion phase did not take place.
The treatment combinations differed by lymphoma population and cohort. Obinutuzumab was used with idasanutlin and venetoclax in the FL plan. For DLBCL, the study evaluated combinations involving rituximab or obinutuzumab during escalation; the expansion plan specified rituximab. The safety cohort used a different venetoclax schedule from the remaining cohorts. Because the arm descriptions in the registry record are incomplete, the full regimen details cannot be established from that record.
Enrollment was 29. The study status is terminated. The record states that the study closed after the benefit was described as mild at escalation doses of 100 mg of idasanutlin with venetoclax 400 mg and 150 mg of idasanutlin with venetoclax 200 mg. It also describes dose-limiting toxicities showing adverse events in all cohorts. These statements provide the recorded rationale and context; they do not constitute a randomized comparison.
Allocation was non-randomized and masking was none. Cohort membership therefore cannot be treated as if participants had been assigned by chance to comparable treatment arms. The registry record does not report a control group, an allocation procedure beyond non-randomization, or a statistical analysis plan.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase. In each DLBCL and FL arm, participants are in Safety Cohort, Cohort 1, Cohort 2, Cohort 3 and Cohort 3- Not defined (DLBCL only). All Adverse Events are reported per Cohort rather than per Arm.
Overall Study
| Stage | Dose Escalation DLBCL and FL Safety Cohort | Dose Escalation DLBCL and FL Cohort 1 | Dose Escalation DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 |
|---|---|---|---|---|---|
| STARTED | 9 | 6 | 7 | 6 | 1 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 9 | 6 | 7 | 6 | 1 |
Reasons for not completing this period:
| Reason | Dose Escalation DLBCL and FL Safety Cohort | Dose Escalation DLBCL and FL Cohort 1 | Dose Escalation DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 |
|---|---|---|---|---|---|
| discontinued due to worsening of pre-existing medical condition | 1 | 0 | 0 | 0 | 0 |
| Progression of disease | 0 | 0 | 0 | 1 | 0 |
| Death | 6 | 2 | 2 | 2 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 |
| Study terminated by sponsor | 2 | 4 | 4 | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population
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 | Dose-Escalation DLBCL and FL Safety Cohort | Dose-Escalation DLBCL and FL Cohort 1 | Dose Escaltion DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 9 | 6 | 7 | 6 | 1 | 29 | |
| Age, Continuous | Years | 58.6 (SD 15.5) | 68.5 (SD 8.7) | 72.4 (SD 8.6) | 74.3 (SD 5.5) | 25.0 (SD 0) | 66.1 (SD 14.4) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 3 | 3 | 0 | 12 |
| Sex: Female, Male: Male | Participants | 6 | 3 | 4 | 3 | 1 | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 6 | 7 | 6 | 1 | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 1 | 2 | 0 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 7 | 5 | 6 | 2 | 1 | 21 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 0 | 1 | 0 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab, measured over Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary measure was the recommended phase II dose of idasanutlin when given with obinutuzumab or rituximab. It was expressed in mg, with a stated assessment timeframe from Cycle 1 Day 1 up to Cycle 2 Day 28, each cycle being 28 days. This is a dose-selection measure rather than a direct estimate of tumor response or survival.
In general, an RP2D is selected to guide later study of a regimen. Dose-escalation studies use safety and tolerability information, including dose-limiting toxicities, to inform whether a dose can be carried forward. The precise decision criteria used in this trial are not reported in the registry record, so the measure should not be interpreted as a dose selected under a known, fully specified rule.
The record says the expansion phase did not take place and that no RP2D was identified in Cohorts 1 and 3. It does not report a complete dose-selection result for every cohort. Consequently, the primary measure does not provide a single identified recommended dose for the overall study population. It also does not, by itself, establish efficacy or compare the combinations.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central result is about feasibility of dose selection, not a definitive comparison of clinical outcomes. The trial was designed to escalate doses and then carry a selected regimen into expansion, but the record says expansion did not occur. It reports that no RP2D was identified in Cohorts 1 and 3. The record does not give a complete RP2D result for every cohort, so the missing cohort-specific result should not be inferred.
The study closed after the sponsor described benefit as mild at the listed escalation doses and reported dose-limiting toxicities showing adverse events in all cohorts. These descriptions are important context for termination, but the registry record does not provide enough statistical detail to quantify benefit, compare doses, or determine how dose-limiting toxicity was defined and adjudicated. The listed doses and combinations should not be read as evidence that one regimen was superior to another.
The registry lists 21 outcome measures, including response measures assessed by investigators or an independent review committee and using PET-CT or CT criteria. However, no numerical response results are reported in the registry record. The number of posted analyses is 0. Without response estimates, denominators for those endpoints, or uncertainty intervals, the response outcomes cannot support a quantitative efficacy interpretation.
Likewise, the non-randomized design limits comparisons between cohorts. Participants were not randomized to a common set of treatment alternatives, and the cohorts may differ in their lymphoma population, dose, schedule, or other characteristics. Apparent differences between cohort results would therefore not isolate a treatment effect. The registry record itself notes that the FL and DLBCL subpopulations showed no difference in genetic subtype make-up, but it does not report the supporting data or a statistical assessment of that statement.
The enrollment of 29 gives the scale of the study, but it does not establish that the study had adequate precision for response or safety estimates. A sample-size justification is not reported in the registry record. In general, small studies can yield imprecise estimates, and the absence of reported confidence intervals makes it difficult to judge the range of values compatible with the observed data. No inferential efficacy conclusion should be drawn from the termination status or dose-selection result alone.
9. Statistical Methods Explained
What the design can establish. General statistical principle: a dose-escalation study primarily gathers information about tolerability across doses and schedules. It is suited to informing dose selection, not to estimating a comparative treatment effect unless it includes an appropriate comparison and analysis. This study was non-randomized and open-label, with a planned escalation followed by expansion. Since expansion did not take place, the registry record describes a study that ended during escalation rather than a completed confirmatory comparison.
Why randomization matters. General statistical principle: randomization helps balance measured and unmeasured participant characteristics between treatment groups on average. Without randomization, differences in outcomes may reflect differences in the participants, disease subtype, dose, schedule, or other factors rather than the treatment combination. The registry record explicitly identifies this as a non-randomized study, and there is no like-for-like control comparison. Cohort-to-cohort contrasts should therefore be read descriptively.
How dose selection is interpreted. General statistical principle: dose selection usually considers the relationship between dose and toxicity, alongside activity and the planned regimen. Dose-limiting toxicity is used to flag adverse effects relevant to escalation decisions. The registry record mentions dose-limiting toxicities and adverse events in all cohorts, but does not report the operational toxicity definition, observation window used for dose-limiting toxicity, decision boundaries, or full dose-by-dose results. Those omissions prevent an independent reconstruction of the selection process.
The primary measure is an RP2D in mg, with a timeframe from Cycle 1 Day 1 up to Cycle 2 Day 28. The registry record states that the intended selection would occur during escalation and be carried into expansion, but that expansion did not take place. It reports no RP2D in Cohorts 1 and 3. The complete selection outcome for Cohort 2 is not reported in the registry record, so it cannot be filled in by assumption.
Uncertainty and inference. General statistical principle: a confidence interval expresses the precision of an estimate by giving a range of values compatible with the data under the method used. No confidence intervals or numerical response estimates are reported for the listed response outcomes. Without estimates and uncertainty intervals, readers cannot assess the precision of response rates or distinguish a stable pattern from a result that could vary substantially with additional observations. No p-values or inferential analyses are posted.
General statistical principle: small cohorts often produce imprecise safety and activity estimates, particularly when outcomes are uncommon. Enrollment was 29, but the registry does not provide a sample-size justification or an analysis plan describing how precision or power was considered. The enrollment count alone cannot show that the study could reliably detect a particular effect.
Planning illustrations. A sample-size calculation is a planning exercise, not a measurement of what a completed trial achieved. The stated illustration framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of an observed effect. For time-to-event outcomes, the stated convention is a total event count; other outcomes use participants per arm. Such illustrations do not establish observed power, and the study’s non-randomized design is not a two-arm randomized comparison. No numerical sample-size results are reported in the registry record.
Over-dispersion and count outcomes. General statistical principle: over-dispersion occurs when count data vary more than a model assumes. If present, standard errors from a model that assumes less variability can be too small, making intervals too narrow and tests too optimistic. The primary measure is a dose level, not a count comparison, and no count-model analysis is reported. The registry record does not report an over-dispersion assessment or a model-based analysis plan.
Multiplicity. The registry lists numerous secondary response outcomes using different assessors and imaging approaches. General statistical principle: making many statistical comparisons can increase the chance of at least one apparently notable result by chance if no adjustment or prespecified interpretation strategy is used. The record does not report a multiplicity plan, and no numerical analyses are posted. It is therefore not possible to determine whether any adjustment was intended or performed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 21 outcome measures, including several versions of complete response and objective response. The measures vary by assessor, imaging basis, and timing. This range of outcomes creates a multiplicity issue if results are tested or interpreted as separate opportunities to find a difference. General statistical principle: a prespecified testing hierarchy or multiplicity adjustment can help control the chance of misleading findings across multiple comparisons. The multiplicity strategy is not reported in the registry record.
Numerical response results, analysis populations for those response outcomes, and methods for handling missing assessments are not reported in the registry record. The record identifies the primary measure’s population as the Safety Population, but does not describe the full analysis populations for the secondary outcomes or how participants with unevaluable scans were handled. No imputation method or missing-data sensitivity analysis is reported.
The number of posted analyses is 0. There are no reported confidence intervals, p-values, or adjusted analyses with which to assess the influence of multiplicity or missing data. General statistical principle: missing outcome data can affect an estimate when the probability of missingness is related to prognosis or treatment experience. Without information on missingness and the analysis rule, that possibility cannot be evaluated.
A statistical analysis plan, interim-analysis plan, and sample-size justification are not reported in the registry record. It is therefore not possible to confirm which outcomes or comparisons were prespecified, whether any interim decisions were planned, or how the reported termination decision related to a formal analysis rule.
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 |
|---|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | 3 | 9 | 33.3% |
| Dose Escalation DLBCL and FL Cohort 1 | 3 | 6 | 50.0% |
| Dose Escalation DLBCL and FL Cohort 2 | 4 | 7 | 57.1% |
| Dose Escalation DLBCL and FL Cohort 3 | 4 | 6 | 66.7% |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | 6 of 9 |
| Dose Escalation DLBCL and FL Cohort 1 | 2 of 6 |
| Dose Escalation DLBCL and FL Cohort 2 | 2 of 7 |
| Dose Escalation DLBCL and FL Cohort 3 | 2 of 6 |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | 9 of 9 |
| Dose Escalation DLBCL and FL Cohort 1 | 6 of 6 |
| Dose Escalation DLBCL and FL Cohort 2 | 7 of 7 |
| Dose Escalation DLBCL and FL Cohort 3 | 6 of 6 |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | 0 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Escalation DLBCL and FL Safety Cohort | Dose Escalation DLBCL and FL Cohort 1 | Dose Escalation DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 |
|---|---|---|---|---|---|---|
| NEUTROPENIA | Blood and lymphatic system disorders | 1 of 9 | 0 of 6 | 1 of 7 | 1 of 6 | 0 of 1 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | 0 of 9 | 0 of 6 | 0 of 7 | 1 of 6 | 0 of 1 |
| ABDOMINAL PAIN | Gastrointestinal disorders | 0 of 9 | 1 of 6 | 0 of 7 | 0 of 6 | 0 of 1 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | 0 of 9 | 0 of 6 | 1 of 7 | 0 of 6 | 0 of 1 |
| NON-CARDIAC CHEST PAIN | General disorders | 0 of 9 | 0 of 6 | 1 of 7 | 0 of 6 | 0 of 1 |
| PYREXIA | General disorders | 0 of 9 | 1 of 6 | 0 of 7 | 0 of 6 | 0 of 1 |
| CHOLECYSTITIS | Hepatobiliary disorders | 0 of 9 | 0 of 6 | 1 of 7 | 0 of 6 | 0 of 1 |
| HYPERBILIRUBINAEMIA | Hepatobiliary disorders | 0 of 9 | 1 of 6 | 0 of 7 | 0 of 6 | 0 of 1 |
| DEVICE RELATED INFECTION | Infections and infestations | 0 of 9 | 0 of 6 | 0 of 7 | 1 of 6 | 0 of 1 |
| PNEUMONIA | Infections and infestations | 0 of 9 | 0 of 6 | 0 of 7 | 1 of 6 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Escalation DLBCL and FL Safety Cohort | Dose Escalation DLBCL and FL Cohort 1 | Dose Escalation DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 |
|---|---|---|---|---|---|---|
| NEUTROPENIA | Blood and lymphatic system disorders | 7 of 9 | 5 of 6 | 7 of 7 | 5 of 6 | n/a of 1 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | 7 of 9 | 4 of 6 | 7 of 7 | 5 of 6 | n/a of 1 |
| DIARRHOEA | Gastrointestinal disorders | 5 of 9 | 3 of 6 | 4 of 7 | 4 of 6 | n/a of 1 |
| NAUSEA | Gastrointestinal disorders | 6 of 9 | 4 of 6 | 3 of 7 | 3 of 6 | n/a of 1 |
| ANAEMIA | Blood and lymphatic system disorders | 4 of 9 | 1 of 6 | 4 of 7 | 3 of 6 | n/a of 1 |
| VOMITING | Gastrointestinal disorders | 3 of 9 | 3 of 6 | 1 of 7 | 2 of 6 | n/a of 1 |
| LEUKOPENIA | Blood and lymphatic system disorders | 3 of 9 | 1 of 6 | 3 of 7 | 1 of 6 | n/a of 1 |
| FATIGUE | General disorders | 1 of 9 | 3 of 6 | 3 of 7 | 1 of 6 | n/a of 1 |
| HEADACHE | Nervous system disorders | 3 of 9 | 1 of 6 | 2 of 7 | 1 of 6 | n/a of 1 |
| CONSTIPATION | Gastrointestinal disorders | 2 of 9 | 1 of 6 | 0 of 7 | 2 of 6 | n/a of 1 |
Serious events with the highest arm-level rate: neutropenia (16.7%), thrombocytopenia (16.7%), abdominal pain (16.7%), pyrexia (16.7%), hyperbilirubinaemia (16.7%).
The adverse-event record separates serious adverse events, other adverse events, and deaths by listed cohort. In the Dose Escalation DLBCL and FL Safety Cohort, 3 of 9 participants were affected by serious adverse events, 9 of 9 by other adverse events, and 6 deaths were recorded. In Cohort 1, the corresponding counts were 3 of 6, 6 of 6, and 2 deaths. In Cohort 2, they were 4 of 7, 7 of 7, and 2 deaths. In Cohort 3, they were 4 of 6, 6 of 6, and 2 deaths. The separately listed group not defined for DLBCL or FL subgroups in Cohort 3 had 0 of 1 affected by serious or other adverse events and 0 deaths.
The registry lists neutropenia, thrombocytopenia, abdominal pain, pyrexia, hyperbilirubinaemia, and device related infection as serious adverse-event terms, each at 16.7%. The denominator and exact basis for these percentages are not reported in the registry record. These event figures are descriptive; they do not establish that an event was caused by study treatment. The relationship of the recorded deaths to treatment, lymphoma, or other causes is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study provides a record of a dose-escalation effort in relapsed or refractory FL and DLBCL, including the treatment combinations considered, cohort-level safety counts, and the decision to stop before expansion. Its primary measure concerned identification of an RP2D, not a randomized estimate of whether one regimen outperformed another. The registry record reports no RP2D for Cohorts 1 and 3 and does not provide a complete result for every cohort.
The record also states that the study closed because benefit was mild at specified escalation doses and that dose-limiting toxicities showed adverse events in all cohorts. This helps explain the recorded course of the study, but the available information does not quantify clinical benefit or establish the cause of individual adverse events. The posted response outcomes have no numerical results, so response rates, differences, and their precision cannot be evaluated.
The results should not be interpreted as proof that the combinations are effective or ineffective. The study was non-randomized, had no like-for-like control comparison, and did not reach its planned expansion phase. The registry does not report the statistical analysis plan, sample-size justification, missing-data procedures, or numerical efficacy analyses. These limitations leave substantial uncertainty about treatment activity and between-cohort differences.
General statistical principle: an early-phase dose-escalation study can inform whether a regimen merits further study, but it usually cannot provide the same evidence as a randomized comparative trial. The status and findings describe what happened in this study; they do not settle what would happen in a different population, setting, or regimen.
13. Why This Trial Matters Statistically
This trial illustrates a statistical distinction between a dose-selection objective and an efficacy comparison. The primary measure was the RP2D of idasanutlin with an antibody, while the broader study also listed response outcomes. Those goals require different forms of evidence: dose selection depends on dose and safety information, whereas a comparative efficacy claim requires interpretable outcome estimates and a suitable comparison.
The planned progression from escalation to expansion is also important. Expansion could have carried a selected regimen into a larger evaluation, but it did not take place. The registry record reports termination during escalation and no RP2D for Cohorts 1 and 3. That leaves the primary dose-selection question only partly answered in the available record and limits what can be learned about later-phase activity.
The design makes careful language essential. Non-randomized cohorts are not equivalent to randomized treatment arms, and any differences among them may reflect more than the regimen. Likewise, the safety counts describe events in the listed cohorts but do not by themselves establish causation. The absence of numerical response analyses and uncertainty estimates further limits quantitative interpretation.
For clinical researchers and biostatisticians, the record is a useful example of why a trial’s intended sequence, endpoint, analysis population, and stopping context all matter. Enrollment and an outcome list do not substitute for reported estimates and methods. Transparent reporting of dose decisions, outcome denominators, missingness, and analysis rules is necessary to understand both what the study learned and what remains uncertain.
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 consequential limitation is that the study ended before its planned expansion phase. The primary measure was intended to identify an RP2D for use in expansion, yet the registry reports no RP2D in Cohorts 1 and 3 and does not give a complete result for every cohort. This prevents a complete account of dose selection across the study.
The design was non-randomized and open-label. It therefore does not support a direct, unbiased comparison among the antibody combinations or between lymphoma populations. The enrollment of 29 also leaves cohort-level safety counts based on small numbers of participants; the registry does not report precision estimates for those counts.
The registry lists response outcomes but does not report their numerical results. It also does not report the analysis plan, sample-size justification, multiplicity handling, missing-data methods, or interim-analysis plan. The full dose-escalation criteria and the definitions and assessment rules for dose-limiting toxicities are not reported in the registry record. Arm descriptions are incomplete, so the full schedules cannot be reconstructed from the record.
Finally, the adverse-event record includes deaths, but their causes and relationship to treatment are not reported. The listed serious adverse-event percentages lack a reported denominator basis. The registry’s statement about genetic subtype make-up is not accompanied by supporting data or a statistical assessment, so it should not be treated as a quantified comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Participants With Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Rituximab in Combination With Idasanutlin and Venetoclax in Participants With R/R Diffuse Large B-Cell Lymphoma (DLBCL) — NCT03135262.
- Registry record last updated 2021-12-07; status last verified 2021-12.
- Results first posted 2021-07-27.
- 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.
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18. Record Summary
NCT03135262 was a Phase Ib/II, open-label, multicenter, non-randomized dose-escalation study sponsored by Hoffmann-La Roche. It enrolled 29 participants with relapsed or refractory FL or DLBCL and evaluated idasanutlin and venetoclax with an antibody. The planned study included dose escalation followed by expansion, but the expansion phase did not take place.
The primary measure was the RP2D of idasanutlin with obinutuzumab or rituximab. The record states that no RP2D was identified in Cohorts 1 and 3 and that the study closed after the benefit was described as mild at specified escalation doses, with dose-limiting toxicities showing adverse events in all cohorts. Numerical response results and statistical analyses are not reported in the registry record.