A Phase 1/2 interventional study of Idasanutlin and Obinutuzumab in Non-Hodgkin's Lymphoma, sponsored by Hoffmann-La Roche. Terminated at 24 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-05-18.
Sponsored by Hoffmann-La Roche · Phase 1/2, Interventional, and Treatment
This is a open-label, multicenter, non-randomized, study to evaluate the safety, efficacy, and pharmacokinetics of idasanutlin in combination with obinutuzumab in participants with R/R FL and rituximab in combination with idasanutlin in R/R DLBCL. The study will include an initial dose-escalation phase followed by an expansion phase. The dose-escalation phase is designed to determine the recommended phase 2 dose (RP2D) for idasanutlin in combination with obinutuzumab for FL and in combination with rituximab for DLBCL. The expansion phase is designed to further assess the safety and efficacy of obinutuzumab in combination with idasanutlin at the RP2D with the selected regimen in participants with R/R FL and of rituximab in combination with idasanutlin at the RP2D in participants with R/R DLBCL.
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Exclusion Criteria:
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).
Drug: Obinutuzumab
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Obinutuzumab
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 200 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Obinutuzumab
Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 150 mg orally in combination with rituximab 375 milligrams per square meter of body surface area (mg/m\^2) IV for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Rituximab
Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 200 mg orally in combination with rituximab 375 mg/m\^2 IV for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Rituximab
Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Obinutuzumab
Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Obinutuzumab
Participants with follicular lymphoma (FL) in this bridging cohort received induction treatment with single-agent obinutuzumab 1000 mg IV for Cycle 1 and then idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for Cycles 2-6 (1 cycle = 28 days).
Drug: Idasanutlin · Drug: Obinutuzumab
Participants received idasanutlin film-coated tablets orally at a starting dose of 100 mg daily on Days 1 to 5 of each 28-day cycle. Escalation was to occur in at least 50-mg increments, and daily doses greater than or equal to (≥) 400 mg will be split into twice daily dosing.
Also known as: RO5503781
Participants received a fixed dose of obinutuzumab 1000 mg intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 (1 cycle = 28 days). For eligible participants with FL, post-induction treatment was to be given at a dose of 1000 mg via IV infusion on Day 1 once every 2 months for a maximum of up to 24 months.
Also known as: RO5072759
Participants received a fixed dose of rituximab, 375 mg/m\^2 IV infusion on Day 1 of Cycles 1-6. Post-induction treatment for eligible participants was to be given at a dose of 375 mg/m\^2 IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.
Also known as: RO0452294
Percentage of Participants With Complete Response at the End of Induction, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
The plan was for the IRC to evaluate responses at the end of induction treatment in participants from the expansion phase using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if indeterminate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Number of Participants With a Dose-Limiting Toxicity
A dose-limiting toxicity (DLT) was defined as at least one of the following events occurring during Cycle 1 (or first 2 cycles in the bridging FL cohort) of treatment and assessed by the investigator as not clearly related to the underlying disease: Any Grade 5 adverse event (AE; severity graded per NCI-CTCAE v4.0) unless due to the underlying malignancy or extraneous causes; AE of any grade that leads to a delay of more than (\>)14 days in the start of the next treatment cycle; Grade 3 or 4 non-hematologic AEs (with exceptions); Lab results suggestive of potential drug-induced liver injury (according to Hy's law); Grade 3 or 4 neutropenia in the presence of sustained fever of \>38 C (lasting \>5 days) or a documented infection; Grade 4 neutropenia or thrombocytopenia lasting \>7 days; Grade 3 or 4 thrombocytopenia if associated with Grade ≥3 bleeding; Other toxicities considered clinically relevant and related to study treatment as determined by the investigator and medical monitor.
Time frame: Cycles 1, 2 (1 cycle is 28 days)
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if indeterminate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions; X = new areas of uptake unlikely to be related to lymphoma). The CR criteria for participants with bone marrow involvement at screening required no evidence of FDG-avid disease in the marrow. PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Complete Response at the End of Induction, Determined by the IRC on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Objective Response at the End of Induction, Determined by the IRC on the Basis of PET-CT Scans Using Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Objective Response at the End of Induction, Determined by an IRC on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Percentage of Participants With Best Response of Complete Response or Partial Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The investigator was to evaluate responses throughout the study using the Lugano 2014 response criteria for malignant lymphoma for a CT-based best response of a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: Baseline, Cycle 2, end of induction (up to 6 cycles; 1 cycle is 28 days), every 2 months (FL) until end of maintenance or at 4 months (DLBCL) of consolidation treatment, and then every 6 months during follow-up until disease progression (up to 3.5 years)
Plasma Idasanutlin Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints Grouped by Idasanutlin Dose and Combination Partner (Obinutuzumab or Rituximab)
The concentration of idasanutlin was determined using a validated assay. The duplication of the predose timepoint (0 hours) on Day 5 as an additional 24-hour timepoint on Day 5 was done in order to conduct pharmacokinetics analysis via non-compartmental analysis, and to derive idasanutlin exposure estimates up to the 24-hour post Day 5 dosing.
Time frame: Predose (0 hours) and 6 hours postdose on Day 1 of Cycles 1, 2, and 4; Predose (0 hours) and 2, 4, 6, and 24 hours postdose on Day 5 of Cycles 1 and 2; Predose (0 hours) and 6 and 24 hours postdose on Cycle 4, Day 5 (1 cycle is 28 days)
Serum Obinutuzumab Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints
Time frame: Pre-infusion (0 hour) and 0.5 hours after end of obinutuzumab infusion on Day 1 of Cycles 1, 2, 4, and 6
Serum Rituximab Concentrations in DLBCL Participants at Nominal Sampling Timepoints
Time frame: Pre-infusion (0 hours) at Cycle 1, Day 1 and Cycle 2, Day 1; Post-infusion 0.5 hours at Cycle 1, Day 1 (1 cycle is 28 days)
Safety Summary of the Number of Participants With at Least One Adverse Event by Type and Severity According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time frame: From first dose until 90 days after the last dose of study drug treatment (up to 31 months)
Baseline Value and Change From Baseline Values of Systolic Blood Pressure at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time frame: Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Baseline Value and Change From Baseline Values of Diastolic Blood Pressure at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time frame: Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Baseline Value and Change From Baseline Values of Pulse Rate at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time frame: Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Baseline Value and Change From Baseline Values of Respiratory Rate at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time frame: Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Baseline Value and Change From Baseline Values of Body Temperature at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time frame: Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Number of Participants by Electrocardiogram (ECG) Results Assessment Shift From Baseline to Specified Post-Baseline Timepoints
Single, resting, 12-lead ECG recordings were to be obtained after the participant had been resting in a supine position for at least 10 minutes. Any morphologic waveform changes or other ECG abnormalities were to be documented and clinical significance was determined based on the presence of symptoms, per the investigator's judgment. If the ECG assessment was missing at baseline then it was recorded as "Missing". The ECG results assessments are presented as the shift from baseline to post-baseline assessments at each timepoint. BL = baseline; Cyc1, D1 = Induction Cycle 1 Day 1; Cyc4, D1 = Induction Cycle 4 Day 1; CS = Clinically Significant; EOI = End of Induction Treatment - Completion/Discontinuation; EOM = End of Maintenance Treatment - Completion/Discontinuation; MM1 = Maintenance Month 1; Unsched = Unscheduled Visit
Time frame: Baseline, Induction Cycle 1 Day 1 and Cycle 4 Day 1, End of Induction (up to 6 cycles; 1 cycle is 28 days); Every 2 months during maintenance treatment from Months 1-23; End of Maintenance (up to 24 months); Unscheduled Visits (as clinically indicated)
Hematology Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. Abs. = absolute count; BL = baseline; WBC = white blood cell count
Time frame: From Baseline until 35 days after the last dose of study drug (up to 29 months)
Blood Chemistry Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Clinical laboratory tests for blood chemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. BL = Baseline; Blood Gluc., Fast. = blood glucose, fasting; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase; Triacylglyc. Lipase = triacylglycerol lipase
Time frame: From Baseline until 35 days after the last dose of study drug (up to 29 months)
| Milestone | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Started | 2 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Received any study treatment | 1 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 2 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Withdrew: Death | 0 | 1 | 2 | 2 | 2 | 0 | 0 | 1 |
| Withdrew: Study terminated by sponsor | 1 | 1 | 0 | 1 | 2 | 2 | 4 | 3 |
| Withdrew: Progressive disease | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
The plan was for the IRC to evaluate responses at the end of induction treatment in participants from the expansion phase using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if indeterminate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
A dose-limiting toxicity (DLT) was defined as at least one of the following events occurring during Cycle 1 (or first 2 cycles in the bridging FL cohort) of treatment and assessed by the investigator as not clearly related to the underlying disease: Any Grade 5 adverse event (AE; severity graded per NCI-CTCAE v4.0) unless due to the underlying malignancy or extraneous causes; AE of any grade that leads to a delay of more than (\>)14 days in the start of the next treatment cycle; Grade 3 or 4 non-hematologic AEs (with exceptions); Lab results suggestive of potential drug-induced liver injury (according to Hy's law); Grade 3 or 4 neutropenia in the presence of sustained fever of \>38 C (lasting \>5 days) or a documented infection; Grade 4 neutropenia or thrombocytopenia lasting \>7 days; Grade 3 or 4 thrombocytopenia if associated with Grade ≥3 bleeding; Other toxicities considered clinically relevant and related to study treatment as determined by the investigator and medical monitor.
| Participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Any DLT | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 1 |
| Thrombocytopenia | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 1 |
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if indeterminate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
| Percentage of participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 0 (0.00 to 77.64) | 33.3 (1.70 to 86.46) | 0 (0.00 to 77.64) | 0 (0.00 to 63.16) | 0 (0.00 to 52.71) | 50.0 (2.53 to 97.47) | 0 (0.00 to 52.71) | 40.0 (7.64 to 81.07) |
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based complete response (CR), which required a complete metabolic response with a score of 1, 2, or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[≤\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions; X = new areas of uptake unlikely to be related to lymphoma). The CR criteria for participants with bone marrow involvement at screening required no evidence of FDG-avid disease in the marrow. PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
| Percentage of participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria | 0 (0.00 to 77.64) | 33.3 (1.70 to 86.46) | 0 (0.00 to 77.64) | 0 (0.00 to 63.16) | 0 (0.00 to 52.71) | 50.0 (2.53 to 97.47) | 0 (0.00 to 52.71) | 40.0 (7.64 to 81.07) |
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
| Percentage of participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria | 0 (0.00 to 77.64) | 33.3 (1.70 to 86.46) | 0 (0.00 to 77.64) | 0 (0.00 to 63.16) | 0 (0.00 to 52.71) | 0 (0.00 to 77.64) | 0 (0.00 to 52.71) | 20.0 (1.02 to 65.74) |
The IRC was to evaluate responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT-based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The investigator was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The investigator was to evaluate responses throughout the study using the Lugano 2014 response criteria for malignant lymphoma for a CT-based best response of a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a ≥50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
No measurements were reported for this outcome.
The concentration of idasanutlin was determined using a validated assay. The duplication of the predose timepoint (0 hours) on Day 5 as an additional 24-hour timepoint on Day 5 was done in order to conduct pharmacokinetics analysis via non-compartmental analysis, and to derive idasanutlin exposure estimates up to the 24-hour post Day 5 dosing.
| nanograms per millilitre (ng/mL) | DLBCL/FL Combined: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL/FL Combined: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 |
|---|---|---|---|---|---|
| Cycle 1, Day 1: 0 hours | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 |
| Cycle 1, Day 1: 6 hours | 1540 ± 21.6 | 2210 ± 42.4 | 5540 ± 21.5 | 2130 ± 91.3 | 2980 ± 49.9 |
| Cycle 1, Day 5: 0 hours | 1150 ± 19.9 | 2150 ± 46.4 | 4120 ± 27.3 | 1660 ± 77.9 | 2920 ± 56.8 |
| Cycle 1, Day 5: 2 hours | 1230 ± 20.8 | 3570 ± 68.4 | 7850 ± 23 | 2970 ± 53.2 | 4970 ± 45.7 |
| Cycle 1, Day 5: 4 hours | 1670 ± 17.5 | 4360 ± 67.6 | 7930 ± 15.5 | 2910 ± 73.2 | 5910 ± 54.6 |
| Cycle 1, Day 5: 6 hours | 1730 ± 15.5 | 4220 ± 94.8 | 7310 ± 13.6 | 2820 ± 68.7 | 5200 ± 49.8 |
| Cycle 1, Day 5: 24 hours | 1150 ± 19.9 | 2150 ± 46.4 | 4120 ± 27.3 | 1660 ± 77.9 | 2920 ± 56.8 |
| Cycle 2, Day 1: 0 hours | 0 ± 0 | 0 ± 0 | — | 0 ± 0 | — |
| Cycle 2, Day 1: 6 hours | 1660 ± 33.1 | 2480 ± 51.5 | — | 1260 ± 49.8 | — |
| Cycle 2, Day 5: 0 hours | — | 2380 ± 27.2 | — | 2400 ± 67 | — |
| Cycle 2, Day 5: 2 hours | — | 4050 ± 54.9 | — | — | — |
| Cycle 2, Day 5: 4 hours | — | 4200 ± 38.2 | — | — | — |
| Cycle 2, Day 5: 6 hours | — | 4010 ± 31.6 | — | — | — |
| Cycle 2, Day 5: 24 hours | — | 2380 ± 27.2 | — | — | — |
| Cycle 4, Day 1: 0 hours | — | 0 ± 0 | — | — | — |
| Cycle 4, Day 1: 6 hours | — | 2730 ± 9.9 | — | — | — |
| Cycle 4, Day 5: 0 hours | — | 2600 ± 25.6 | — | — | — |
| Cycle 4, Day 5: 6 hours | — | 5210 ± 19.5 | — | — | — |
| Cycle 4, Day 5: 24 hours | — | 2600 ± 25.6 | — | — | — |
| micrograms per millilitre (μg/mL) | DLBCL/FL: Idasanutlin 100/150/200 mg + Obinutuzumab 1000 mg |
|---|---|
| Cycle 1, Day 1: 0 hours | 0 ± 0 |
| Cycle 1, Day 1: 0.5 hours | 397 ± 32.9 |
| Cycle 2, Day 1: 0 hours | 325 ± 59.8 |
| Cycle 2, Day 1: 0.5 hours | 703 ± 40.2 |
| Cycle 4, Day 1: 0 hours | 346 ± 46.1 |
| Cycle 4, Day 1: 0.5 hours | 685 ± 38.5 |
| Cycle 6, Day 1: 0 hours | 303 ± 49.5 |
| Cycle 6, Day 1: 0.5 hours | 639 ± 34.2 |
| micrograms per millilitre (μg/mL) | DLBCL Combined: Idasanutlin 150/200 mg + Rituximab 375 mg/m^2 |
|---|---|
| Cycle 1, Day 1: 0 hours | 0 ± 0 |
| Cycle 1, Day 1: 0.5 hours | 197 ± 14.1 |
| Cycle 2, Day 1: 0 hours | 37.9 ± 58.1 |
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
| Participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Any Adverse Event (AE) | 1 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Grade 5 AE | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 3-5 AE | 1 | 3 | 2 | 2 | 3 | 1 | 3 | 4 |
| Serious AE | 1 | 1 | 1 | 0 | 2 | 1 | 1 | 2 |
| AE Leading to any Study Treatment Discontinuation | 0 | 1 | 2 | 1 | 1 | 0 | 2 | 2 |
| AE Leading to Dose Reductions | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| AE Leading to Dose Interruptions | 1 | 0 | 0 | 0 | 1 | 0 | 3 | 1 |
| AE Leading to Study Discontinuation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Related to Idasanutlin - Any AE | 1 | 2 | 2 | 2 | 4 | 1 | 4 | 5 |
| Related to Idasanutlin - Grade 3-5 AE | 1 | 2 | 2 | 1 | 2 | 1 | 3 | 4 |
| Related to Idasanutlin - Serious AE | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 2 |
| Related to Obinutuzumab - Any AE | 1 | 2 | 2 | 0 | 1 | 0 | 3 | 5 |
| Related to Obinutuzumab - Grade 3-5 AE | 1 | 1 | 2 | 0 | 0 | 0 | 2 | 3 |
| Related to Obinutuzumab - Serious AE | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 |
| Related to Rituximab - Any AE | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 |
| Related to Rituximab - Grade 3-5 AE | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Related to Rituximab - Serious AE | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Related AE Leading to Treatment Discontinuation | 0 | 0 | 2 | 1 | 1 | 0 | 2 | 1 |
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
| millimeters of mercury (mmHg) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline (BL) - Value at Visit | 176.0 ± NA | 124.0 ± 7.9 | 107.5 ± 2.1 | 125.7 ± 39.4 | 119.0 ± 16.8 | 120.5 ± 17.7 | 109.3 ± 9.1 | 116.4 ± 10.5 |
| Change from BL at Cycle 1 Day 1 | -34.0 ± NA | -2.0 ± 10.5 | -5.0 ± 4.2 | -2.7 ± 14.6 | -0.8 ± 10.6 | -3.5 ± 10.6 | 3.5 ± 9.4 | 4.8 ± 14.8 |
| Change from BL at Cycle 1 Day 8 | -4.0 ± NA | -5.0 ± 8.5 | -7.0 ± 8.5 | — | — | -6.5 ± 6.4 | -2.3 ± 15.2 | 6.4 ± 10.3 |
| Change from BL at Cycle 1 Day 15 | 24.0 ± NA | -5.3 ± 14.6 | — | — | — | -3.5 ± 7.8 | 9.7 ± 13.4 | 8.0 ± 12.9 |
| Change from BL at Cycle 2 Day 1 | -17.0 ± NA | -3.5 ± 19.1 | — | 0.0 ± 39.6 | — | -14.0 ± NA | 4.5 ± 4.9 | 8.6 ± 10.4 |
| Change from BL at Cycle 3 Day 1 | -1.0 ± NA | 11.0 ± NA | — | — | — | -13.5 ± 3.5 | 10.5 ± 2.1 | 7.0 ± 8.9 |
| Change from BL at Cycle 4 Day 1 | -22.0 ± NA | — | — | — | — | 12.5 ± 27.6 | 2.0 ± 1.4 | -10.0 ± NA |
| Change from BL at Cycle 5 Day 1 | -21.0 ± NA | — | — | — | — | 0.5 ± 4.9 | 12.5 ± 9.2 | 8.5 ± 9.2 |
| Change from BL at Cycle 6 Day 1 | — | — | — | — | — | -2.0 ± NA | 20.0 ± NA | 0.5 ± 0.7 |
| Change from BL at Maint. Month 1 | — | — | — | — | — | -14.0 ± NA | — | 14.0 ± 9.9 |
| Change from BL at Maint. Month 3 | — | — | — | — | — | 9.0 ± NA | — | 7.5 ± 10.6 |
| Change from BL at Maint. Month 5 | — | — | — | — | — | -12.0 ± NA | — | 9.0 ± NA |
| Change from BL at Maint. Month 7 | — | — | — | — | — | -5.0 ± NA | — | 0.0 ± NA |
| Change from BL at Maint. Month 9 | — | — | — | — | — | -3.0 ± NA | — | 7.0 ± NA |
| Change from BL at Maint. Month 11 | — | — | — | — | — | -5.0 ± NA | — | — |
| Change from BL at Maint. Month 13 | — | — | — | — | — | -5.0 ± NA | — | — |
| Change from BL at Maint. Month 15 | — | — | — | — | — | -9.0 ± NA | — | — |
| Change from BL at Maint. Month 17 | — | — | — | — | — | -35.0 ± NA | — | — |
| Change from BL at Maint. Month 19 | — | — | — | — | — | 2.0 ± NA | — | — |
| Change from BL at Maint. Month 21 | — | — | — | — | — | -21.0 ± NA | — | — |
| Change from BL at Follow-Up | -32.0 ± NA | — | -3.5 ± 9.2 | -25.0 ± 55.2 | -3.5 ± 0.7 | 9.5 ± 3.5 | 20.0 ± 15.5 | -1.3 ± 9.0 |
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
| millimeters of mercury (mmHg) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline (BL) - Value at Visit | 100.0 ± NA | 67.3 ± 12.1 | 72.0 ± 9.9 | 72.3 ± 12.3 | 70.3 ± 7.6 | 71.5 ± 9.2 | 76.3 ± 12.7 | 65.8 ± 6.9 |
| Change from BL at Cycle 1 Day 1 | -17.0 ± NA | -2.0 ± 19.5 | -2.5 ± 2.1 | 7.3 ± 23.1 | -2.3 ± 7.4 | -2.0 ± 4.2 | 3.0 ± 4.9 | 6.4 ± 2.1 |
| Change from BL at Cycle 1 Day 8 | -1.0 ± NA | 1.3 ± 15.0 | -2.5 ± 6.4 | — | — | -2.0 ± 0.0 | -6.5 ± 1.3 | 9.2 ± 8.5 |
| Change from BL at Cycle 1 Day 15 | -1.0 ± NA | 3.0 ± 16.4 | — | — | — | 6.0 ± 4.2 | 0.0 ± 6.6 | 2.4 ± 8.3 |
| Change from BL at Cycle 2 Day 1 | 7.0 ± NA | 0.0 ± 17.0 | — | 3.5 ± 13.4 | — | 0.0 ± NA | -8.0 ± 2.8 | 12.0 ± 5.1 |
| Change from BL at Cycle 3 Day 1 | 3.0 ± NA | 3.0 ± NA | — | — | — | -5.5 ± 6.4 | -1.0 ± 4.2 | 5.3 ± 5.0 |
| Change from BL at Cycle 4 Day 1 | -4.0 ± NA | — | — | — | — | 3.0 ± 8.5 | -8.0 ± 7.1 | 7.0 ± NA |
| Change from BL at Cycle 5 Day 1 | -2.0 ± NA | — | — | — | — | 3.5 ± 0.7 | -2.0 ± 7.1 | 2.5 ± 4.9 |
| Change from BL at Cycle 6 Day 1 | — | — | — | — | — | 10.0 ± NA | 9.0 ± NA | 2.5 ± 3.5 |
| Change from BL at Maint. Month 1 | — | — | — | — | — | 0.0 ± NA | — | 2.0 ± 0.0 |
| Change from BL at Maint. Month 3 | — | — | — | — | — | 14.0 ± NA | — | 5.0 ± 8.5 |
| Change from BL at Maint. Month 5 | — | — | — | — | — | -7.0 ± NA | — | -5.0 ± NA |
| Change from BL at Maint. Month 7 | — | — | — | — | — | 7.0 ± NA | — | -1.0 ± NA |
| Change from BL at Maint. Month 9 | — | — | — | — | — | 6.0 ± NA | — | 3.0 ± NA |
| Change from BL at Maint. Month 11 | — | — | — | — | — | -13.0 ± NA | — | — |
| Change from BL at Maint. Month 13 | — | — | — | — | — | 1.0 ± NA | — | — |
| Change from BL at Maint. Month 15 | — | — | — | — | — | 9.0 ± NA | — | — |
| Change from BL at Maint. Month 17 | — | — | — | — | — | -4.0 ± NA | — | — |
| Change from BL at Maint. Month 19 | — | — | — | — | — | 7.0 ± NA | — | — |
| Change from BL at Maint. Month 21 | — | — | — | — | — | 0.0 ± NA | — | — |
| Change from BL at Follow-Up | -16.0 ± NA | — | -9.0 ± 21.2 | -15.5 ± 20.5 | 4.0 ± 4.2 | 10.5 ± 2.1 | 7.5 ± 20.2 | 9.3 ± 3.3 |
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
| beats per minute | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline (BL) - Value at Visit | 73.0 ± NA | 65.7 ± 1.2 | 100.5 ± 17.7 | 81.7 ± 3.1 | 76.0 ± 10.6 | 77.5 ± 12.0 | 79.5 ± 18.6 | 80.2 ± 9.9 |
| Change from BL at Cycle 1 Day 1 | 10.0 ± NA | 15.7 ± 21.5 | -9.0 ± 8.5 | 0.0 ± 9.8 | 8.8 ± 12.0 | 2.5 ± 14.8 | 2.3 ± 6.4 | 9.0 ± 11.1 |
| Change from BL at Cycle 1 Day 8 | -2.0 ± NA | 11.0 ± 2.0 | -2.0 ± 1.4 | — | — | -0.5 ± 20.5 | 2.3 ± 6.4 | 9.0 ± 11.1 |
| Change from BL at Cycle 1 Day 15 | -11.0 ± NA | 12.7 ± 13.4 | — | — | — | -3.5 ± 16.3 | -1.7 ± 13.1 | 3.2 ± 14.5 |
| Change from BL at Cycle 2 Day 1 | 4.0 ± NA | 17.5 ± 17.7 | — | 7.0 ± 1.4 | — | -17.0 ± NA | -2.5 ± 4.9 | 6.4 ± 9.7 |
| Change from BL at Cycle 3 Day 1 | -1.0 ± NA | 19.0 ± NA | — | — | — | -1.5 ± 16.3 | -4.5 ± 20.5 | -3.5 ± 10.6 |
| Change from BL at Cycle 4 Day 1 | 1.0 ± NA | — | — | — | — | -7.0 ± 12.7 | -5.0 ± 5.7 | 4.0 ± NA |
| Change from BL at Cycle 5 Day 1 | 15.0 ± NA | — | — | — | — | -6.5 ± 10.6 | 3.0 ± 28.3 | 6.5 ± 4.9 |
| Change from BL at Cycle 6 Day 1 | — | — | — | — | — | -1.0 ± NA | 31.0 ± NA | 15.0 ± 2.8 |
| Change from BL at Maint. Month 1 | — | — | — | — | — | 6.0 ± NA | — | 10.0 ± 5.7 |
| Change from BL at Maint. Month 3 | — | — | — | — | — | 0.0 ± NA | — | 2.0 ± 9.9 |
| Change from BL at Maint. Month 5 | — | — | — | — | — | -5.0 ± NA | — | 11.0 ± NA |
| Change from BL at Maint. Month 7 | — | — | — | — | — | 1.0 ± NA | — | 2.0 ± NA |
| Change from BL at Maint. Month 9 | — | — | — | — | — | 6.0 ± NA | — | 11.0 ± NA |
| Change from BL at Maint. Month 11 | — | — | — | — | — | 18.0 ± NA | — | — |
| Change from BL at Maint. Month 13 | — | — | — | — | — | 11.0 ± NA | — | — |
| Change from BL at Maint. Month 15 | — | — | — | — | — | 2.0 ± NA | — | — |
| Change from BL at Maint. Month 17 | — | — | — | — | — | -2.0 ± NA | — | — |
| Change from BL at Maint. Month 19 | — | — | — | — | — | 1.0 ± NA | — | — |
| Change from BL at Maint. Month 21 | — | — | — | — | — | 13.0 ± NA | — | — |
| Change from BL at Follow-Up | 15.0 ± NA | — | -20.0 ± 18.4 | 11.5 ± 10.6 | 23.5 ± 20.5 | 15.0 ± 8.5 | 5.8 ± 14.8 | 10.3 ± 9.2 |
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
| breaths per minute | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline (BL) - Value at Visit | 18.0 ± NA | 17.0 ± 2.6 | 19.0 ± 1.4 | 17.0 ± 1.7 | 17.0 ± 2.0 | 16.0 ± 0.0 | 16.0 ± 3.3 | 16.8 ± 3.0 |
| Change from BL at Cycle 1 Day 1 | 0.0 ± NA | 0.7 ± 1.2 | -1.0 ± 1.4 | -0.7 ± 1.2 | 0.3 ± 1.3 | 1.0 ± 1.4 | 2.3 ± 0.5 | 0.0 ± 0.0 |
| Change from BL at Cycle 1 Day 8 | 0.0 ± NA | -1.7 ± 2.1 | -1.0 ± 1.4 | — | — | 0.0 ± 0.0 | 2.0 ± 4.0 | 0.0 ± 2.4 |
| Change from BL at Cycle 1 Day 15 | 0.0 ± NA | -3.5 ± 2.1 | — | — | — | 1.0 ± 1.4 | 1.7 ± 1.5 | -0.2 ± 2.7 |
| Change from BL at Cycle 2 Day 1 | 0.0 ± NA | -2.5 ± 3.5 | — | 0.5 ± 0.7 | — | 0.0 ± NA | 4.0 ± 5.7 | 0.0 ± 4.6 |
| Change from BL at Cycle 3 Day 1 | 2.0 ± NA | -4.0 ± NA | — | — | — | 0.0 ± 0.0 | 4.0 ± 5.7 | -1.0 ± 4.2 |
| Change from BL at Cycle 4 Day 1 | -2.0 ± NA | — | — | — | — | 0.0 ± 0.0 | 2.0 ± 2.8 | 4.0 ± NA |
| Change from BL at Cycle 5 Day 1 | 0.0 ± NA | — | — | — | — | 0.0 ± 0.0 | 1.0 ± 1.4 | 0.0 ± 5.7 |
| Change from BL at Cycle 6 Day 1 | — | — | — | — | — | -4.0 ± NA | 5.0 ± NA | -2.0 ± 2.8 |
| Change from BL at Maint. Month 1 | — | — | — | — | — | -4.0 ± NA | — | -1.0 ± 4.2 |
| Change from BL at Maint. Month 3 | — | — | — | — | — | 0.0 ± NA | — | -2.0 ± 2.8 |
| Change from BL at Maint. Month 5 | — | — | — | — | — | 0.0 ± NA | — | -4.0 ± NA |
| Change from BL at Maint. Month 7 | — | — | — | — | — | 0.0 ± NA | — | -4.0 ± NA |
| Change from BL at Maint. Month 9 | — | — | — | — | — | 2.0 ± NA | — | -4.0 ± NA |
| Change from BL at Maint. Month 11 | — | — | — | — | — | 0.0 ± NA | — | — |
| Change from BL at Maint. Month 13 | — | — | — | — | — | 0.0 ± NA | — | — |
| Change from BL at Maint. Month 15 | — | — | — | — | — | 0.0 ± NA | — | — |
| Change from BL at Maint. Month 17 | — | — | — | — | — | 2.0 ± NA | — | — |
| Change from BL at Maint. Month 19 | — | — | — | — | — | 0.0 ± NA | — | — |
| Change from BL at Maint. Month 21 | — | — | — | — | — | 2.0 ± NA | — | — |
| Change from BL at Follow-Up | -2.0 ± NA | — | -2.0 ± 2.8 | -4.0 ± NA | 0.0 ± 2.8 | 1.0 ± 1.4 | 3.3 ± 3.2 | -0.7 ± 3.1 |
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
| degrees Celsius (C) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline (BL) - Value at Visit | 36.60 ± NA | 36.47 ± 0.45 | 36.35 ± 0.21 | 36.83 ± 0.15 | 36.58 ± 0.34 | 36.55 ± 0.21 | 36.50 ± 0.18 | 36.70 ± 3.3 |
| Change from BL at Cycle 1 Day 1 | 0.00 ± NA | 0.00 ± 0.92 | -0.15 ± 0.21 | -0.07 ± 0.15 | 0.18 ± 0.33 | 0.05 ± 0.49 | 0.30 ± 0.22 | -0.18 ± 0.30 |
| Change from BL at Cycle 1 Day 8 | 0.10 ± NA | 0.37 ± 0.50 | 0.95 ± 0.85 | — | — | 0.30 ± 0.28 | -0.13 ± 0.22 | 0.10 ± 0.45 |
| Change from BL at Cycle 1 Day 15 | 0.10 ± NA | 0.20 ± 0.82 | — | — | — | 0.20 ± 0.28 | -0.23 ± 0.45 | -0.18 ± 0.26 |
| Change from BL at Cycle 2 Day 1 | 0.00 ± NA | 0.10 ± 0.14 | — | -0.30 ± 0.14 | — | -0.50 ± NA | -0.25 ± 0.49 | -0.04 ± 0.09 |
| Change from BL at Cycle 3 Day 1 | -0.20 ± NA | -0.10 ± NA | — | — | — | -0.10 ± 0.42 | -0.50 ± 0.28 | -0.17 ± 0.21 |
| Change from BL at Cycle 4 Day 1 | 0.00 ± NA | — | — | — | — | 0.05 ± 0.64 | 0.05 ± 0.21 | -0.10 ± NA |
| Change from BL at Cycle 5 Day 1 | 0.20 ± NA | — | — | — | — | 0.35 ± 0.64 | -0.35 ± 0.49 | -0.20 ± 0.14 |
| Change from BL at Cycle 6 Day 1 | — | — | — | — | — | 0.20 ± NA | 0.20 ± NA | -0.05 ± 0.21 |
| Change from BL at Maint. Month 1 | — | — | — | — | — | 0.60 ± NA | — | -0.20 ± 0.14 |
| Change from BL at Maint. Month 3 | — | — | — | — | — | 0.40 ± NA | — | -0.20 ± 0.57 |
| Change from BL at Maint. Month 5 | — | — | — | — | — | 0.20 ± NA | — | -0.20 ± NA |
| Change from BL at Maint. Month 7 | — | — | — | — | — | 0.60 ± NA | — | -0.10 ± NA |
| Change from BL at Maint. Month 9 | — | — | — | — | — | 0.30 ± NA | — | 0.20 ± NA |
| Change from BL at Maint. Month 11 | — | — | — | — | — | 0.70 ± NA | — | — |
| Change from BL at Maint. Month 13 | — | — | — | — | — | 0.40 ± NA | — | — |
| Change from BL at Maint. Month 15 | — | — | — | — | — | 0.70 ± NA | — | — |
| Change from BL at Maint. Month 17 | — | — | — | — | — | 0.40 ± NA | — | — |
| Change from BL at Maint. Month 19 | — | — | — | — | — | 0.80 ± NA | — | — |
| Change from BL at Maint. Month 21 | — | — | — | — | — | 0.50 ± NA | — | — |
| Change from BL at Follow-Up | 0.10 ± NA | — | 0.00 ± 0.14 | -0.40 ± 0.14 | 0.53 ± 0.71 | 0.30 ± 0.57 | -0.15 ± 0.47 | -0.10 ± 0.24 |
Single, resting, 12-lead ECG recordings were to be obtained after the participant had been resting in a supine position for at least 10 minutes. Any morphologic waveform changes or other ECG abnormalities were to be documented and clinical significance was determined based on the presence of symptoms, per the investigator's judgment. If the ECG assessment was missing at baseline then it was recorded as "Missing". The ECG results assessments are presented as the shift from baseline to post-baseline assessments at each timepoint. BL = baseline; Cyc1, D1 = Induction Cycle 1 Day 1; Cyc4, D1 = Induction Cycle 4 Day 1; CS = Clinically Significant; EOI = End of Induction Treatment - Completion/Discontinuation; EOM = End of Maintenance Treatment - Completion/Discontinuation; MM1 = Maintenance Month 1; Unsched = Unscheduled Visit
| Participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Cyc1, D1: Normal (BL) to Normal | — | 1 | 1 | 0 | 2 | 0 | 4 | 2 |
| Cyc1, D1: Normal (BL) to Abnormal, not CS | — | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Cyc1, D1: Abnormal, not CS (BL) to Normal | — | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Cyc1,D1: Abnormal, not CS (BL) to Abnormal, not CS | — | 1 | 1 | 1 | 2 | 1 | 0 | 2 |
| Cyc4, D1: Normal (BL) to Normal | 0 | — | — | — | — | 0 | 2 | 1 |
| Cyc4, D1: Normal (BL) to Abnormal, not CS | 1 | — | — | — | — | 0 | 0 | 0 |
| Cyc4, D1: Abnormal, not CS (BL) to Normal | 0 | — | — | — | — | 0 | 0 | 1 |
| Cyc4,D1: Abnormal, not CS (BL) to Abnormal, not CS | 0 | — | — | — | — | 1 | 0 | 0 |
| Cyc4, D1: Missing (BL) to Normal | 0 | — | — | — | — | 1 | 0 | 0 |
| EOI: Normal (BL) to Normal | 0 | 0 | 1 | 0 | 2 | 0 | 3 | 2 |
| EOI: Normal (BL) to Abnormal, not CS | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| EOI: Abnormal, not CS (BL) to Abnormal, not CS | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 |
| EOI: Missing (BL) to Normal | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| MM1: Normal (BL) to Normal | — | — | — | — | — | — | — | 1 |
| MM1: Abnormal, not CS (BL) to Abnormal, not CS | — | — | — | — | — | — | — | 1 |
| MM3: Abnormal, not CS (BL) to Normal | — | — | — | — | — | — | — | 1 |
| MM5: Abnormal, not CS (BL) to Normal | — | — | — | — | — | — | — | 1 |
| MM7: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM9: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM11: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM13: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM15: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM17: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM19: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM21: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| MM23: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | — | — |
| EOM: Normal (BL) to Normal | — | — | — | — | — | 0 | 1 | — |
| EOM: Missing (BL) to Abnormal, not CS | — | — | — | — | — | 1 | 0 | — |
| Unsched: Normal (BL) to Normal | 1 | — | — | — | — | 0 | 1 | 0 |
| Unsched: Normal (BL) to Abnormal, not CS | 0 | — | — | — | — | 0 | 1 | 0 |
| Unsched: Abnormal, not CS (BL) to Normal | 0 | — | — | — | — | 0 | 0 | 1 |
| Unsched: Abnormal, not CS (BL) to Abnormal, not CS | 0 | — | — | — | — | 1 | 0 | 0 |
| Unsched: Abnormal, not CS (BL) to Abnormal, CS | 0 | — | — | — | — | 0 | 0 | 1 |
Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. Abs. = absolute count; BL = baseline; WBC = white blood cell count
| Participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Hemoglobin (g/L), High: Grade (Gr.) 0 (BL) to 0 | 1 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Hemoglobin (g/L), Low: Gr. 0 (BL) to 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Hemoglobin (g/L), Low: Gr. 0 (BL) to 2 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Hemoglobin (g/L), Low: Gr. 0 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Hemoglobin (g/L), Low: Gr. 1 (BL) to 1 | 0 | 2 | 0 | 2 | 3 | 0 | 1 | 1 |
| Hemoglobin (g/L), Low: Gr. 1 (BL) to 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 2 |
| Hemoglobin (g/L), Low: Gr. 1 (BL) to 3 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin (g/L), Low: Gr. 2 (BL) to 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Hemoglobin (g/L), Low: Gr. 2 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Hemoglobin (g/L), Low: Gr. 3 (BL) to 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 0 (BL) to 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 0 (BL) to 2 | 1 | 0 | 0 | 1 | 2 | 0 | 1 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 0 (BL) to 3 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 0 (BL) to 4 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 1 (BL) to 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 1 (BL) to 3 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 2 (BL) to 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 2 (BL) to 4 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 3 (BL) to 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 3 (BL) to 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 3 (BL) to 4 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocytes Abs. (10^9/L), Low: Gr. 4 (BL) to 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 0(BL) to 0 | 0 | 2 | 0 | 2 | 2 | 0 | 1 | 2 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 0(BL) to 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 0(BL) to 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 0(BL) to 3 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 0(BL) to 4 | 0 | 0 | 2 | 0 | 0 | 1 | 2 | 1 |
| Neutrophils,Total Abs (10^9/L),Low: Gr. 2(BL) to 4 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Platelets (10^9/L), Low: Gr. 0 (BL) to 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Platelets (10^9/L), Low: Gr. 0 (BL) to 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 |
| Platelets (10^9/L), Low: Gr. 0 (BL) to 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Platelets (10^9/L), Low: Gr. 0 (BL) to 3 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Platelets (10^9/L), Low: Gr. 0 (BL) to 4 | 0 | 0 | 2 | 1 | 2 | 1 | 2 | 1 |
| Platelets (10^9/L), Low: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Platelets (10^9/L), Low: Gr. 1 (BL) to 3 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Platelets (10^9/L), Low: Gr. 1 (BL) to 4 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| WBC (10^9/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 4 | 2 | 4 | 5 |
| WBC (10^9/L), Low: Gr. 0 (BL) to 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 1 |
| WBC (10^9/L), Low: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| WBC (10^9/L), Low: Gr. 0 (BL) to 2 | 1 | 2 | 0 | 1 | 0 | 1 | 1 | 0 |
| WBC (10^9/L), Low: Gr. 0 (BL) to 3 | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 0 |
| WBC (10^9/L), Low: Gr. 0 (BL) to 4 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| WBC (10^9/L), Low: Gr. 1 (BL) to 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| WBC (10^9/L), Low: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| WBC (10^9/L), Low: Gr. 1 (BL) to 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| WBC (10^9/L), Low: Gr. 1 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Clinical laboratory tests for blood chemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. BL = Baseline; Blood Gluc., Fast. = blood glucose, fasting; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase; Triacylglyc. Lipase = triacylglycerol lipase
| Participants | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Albumin (g/L), Low: Grade (Gr.) 0 (BL) to 0 | 1 | 3 | 2 | 1 | 2 | 2 | 4 | 3 |
| Albumin (g/L), Low: Grade (Gr.) 0 (BL) to 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Albumin (g/L), Low: Grade (Gr.) 0 (BL) to 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Albumin (g/L), Low: Grade (Gr.) 1 (BL) to 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Alkaline Phosphatase (U/L), High: Gr. 0 (BL) to 0 | 0 | 3 | 2 | 2 | 3 | 1 | 4 | 3 |
| Alkaline Phosphatase (U/L), High: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
| Alkaline Phosphatase (U/L), High: Gr. 1 (BL) to 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Amylase (U/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 1 | 2 | 3 | 5 |
| Amylase (U/L), High: Missing (BL) to Gr. 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Amylase (U/L), High: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Bilirubin (umol/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 4 | 2 | 3 | 5 |
| Bilirubin (umol/L), High: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Blood Gluc,Fast(mmol/L), High: Missing(BL) to Gr 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Blood Gluc,Fast(mmol/L), High: Gr. 0(BL) to 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood Gluc,Fast(mmol/L), High: Gr. 1 (BL) to 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood Gluc,Fast(mmol/L), High: Missing(BL) to Gr 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood Gluc.,Fast.(mmol/L), High: Missing (All) | 0 | 3 | 0 | 3 | 4 | 1 | 3 | 4 |
| Blood Gluc,Fast(mmol/L), Low: Gr. 0 (BL) to 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Blood Gluc,Fast(mmol/L), Low: Missing(BL) to Gr 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Blood Gluc.,Fast.(mmol/L), Low: Missing (All) | 0 | 3 | 0 | 3 | 4 | 1 | 3 | 4 |
| Calcium (mmol/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 3 | 2 | 4 | 5 |
| Calcium (mmol/L), High: Gr. 1 (BL) to 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Calcium (mmol/L), Low: Gr. 0 (BL) to 0 | 1 | 2 | 2 | 2 | 3 | 2 | 3 | 4 |
| Calcium (mmol/L), Low: Gr. 0 (BL) to 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 |
| Calcium (mmol/L), Low: Gr. 0 (BL) to 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Calcium (mmol/L), Low: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Creatinine (umol/L), High: Gr. 0 (BL) to 0 | 0 | 2 | 0 | 1 | 0 | 0 | 2 | 3 |
| Creatinine (umol/L), High: Gr. 0 (BL) to 1 | 0 | 1 | 2 | 2 | 2 | 2 | 1 | 1 |
| Creatinine (umol/L), High: Gr. 0 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Creatinine (umol/L), High: Gr. 1 (BL) to 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Creatinine (umol/L), High: Gr. 1 (BL) to 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Creatinine (umol/L), High: Gr. 1 (BL) to 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Glucose (mmol/L), High: Gr. 0 (BL) to 0 | 0 | 3 | 0 | 3 | 4 | 2 | 4 | 5 |
| Glucose (mmol/L), High: Missing (BL) to Gr. 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Glucose (mmol/L), High: Gr. 0 (BL) to 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose (mmol/L), High: Missing (All) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Glucose (mmol/L), Low: Gr. 0 (BL) to 0 | 1 | 2 | 0 | 2 | 4 | 2 | 4 | 4 |
| Glucose (mmol/L), Low: Missing (BL) to Gr. 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Glucose (mmol/L), Low: Gr. 0 (BL) to 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 |
| Glucose (mmol/L), Low: Missing (All) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Phosphorus (mmol/L), Low: Gr. 0 (BL) to 0 | 0 | 2 | 2 | 1 | 2 | 0 | 0 | 2 |
| Phosphorus (mmol/L), Low: Missing (BL) to Gr. 0 | 1 | 1 | 0 | 1 | 0 | 0 | 2 | 1 |
| Phosphorus (mmol/L), Low: Missing (BL) to Gr. 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Phosphorus (mmol/L), Low: Missing (All) | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 2 |
| Potassium (mmol/L), High: Gr. 0 (BL) to 0 | 0 | 3 | 2 | 2 | 4 | 2 | 4 | 5 |
| Potassium (mmol/L), High: Gr. 0 (BL) to 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Potassium (mmol/L), Low: Gr. 0 (BL) to 0 | 1 | 2 | 2 | 3 | 3 | 2 | 4 | 3 |
| Potassium (mmol/L), Low: Gr. 0 (BL) to 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Potassium (mmol/L), Low: Gr. 2 (BL) to 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Potassium (mmol/L), Low: Gr. 2 (BL) to 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| SGOT/AST (U/L), High: Gr. 0 (BL) to 0 | 1 | 2 | 2 | 2 | 4 | 2 | 4 | 5 |
| SGOT/AST (U/L), High: Gr. 1 (BL) to 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| SGPT/ALT (U/L), High: Gr. 0 (BL) to 0 | 1 | 2 | 1 | 3 | 2 | 2 | 4 | 5 |
| SGPT/ALT (U/L), High: Gr. 1 (BL) to 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| SGPT/ALT (U/L), High: Gr. 1 (BL) to 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Sodium (mmol/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 3 | 2 | 4 | 4 |
| Sodium (mmol/L), High: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Sodium (mmol/L), High: Gr. 1 (BL) to 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Sodium (mmol/L), Low: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 2 | 4 | 2 | 4 | 3 |
| Sodium (mmol/L), Low: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Sodium (mmol/L), Low: Gr. 0 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Sodium (mmol/L), Low: Gr. 1 (BL) to 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Triacylglyc. Lipase (U/L), High: Gr. 0 (BL) to 0 | 0 | 3 | 2 | 3 | 2 | 1 | 3 | 4 |
| Triacylglyc. Lipase (U/L), High: Gr. 0 (BL) to 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Triacylglyc. Lipase (U/L), High: Gr. 0 (BL) to 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Triacylglyc Lipase (U/L),High: Missing(BL) to Gr 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Triacylglyc Lipase (U/L),High: Missing(BL) to Gr 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Uric Acid (umol/L), High: Gr. 0 (BL) to 0 | 1 | 3 | 2 | 3 | 2 | 2 | 3 | 4 |
| Uric Acid (umol/L), High: Missing(BL) to Gr. 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Uric Acid (umol/L), High: Gr. 0 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Uric Acid (umol/L), High: Gr. 3 (BL) to 3 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Uric Acid (umol/L), High: Gr. 4 (BL) to 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Collected over From first dose until 90 days after the last dose of study drug treatment (up to 31 months), except for serious AEs related to treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | 2/2 (100%) | 1/2 (50%) | 2/2 (100%) |
| DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | 2/3 (66.7%) | 0/3 (0%) | 3/3 (100%) |
| DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | 2/4 (50%) | 2/4 (50%) | 4/4 (100%) |
| FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | 0/2 (0%) | 1/2 (50%) | 2/2 (100%) |
| FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | 0/4 (0%) | 1/4 (25%) | 4/4 (100%) |
| FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | 1/5 (20%) | 2/5 (40%) | 5/5 (100%) |
| Event | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 1/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 1/5 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/1 | 0/3 | 0/2 | 0/3 | 1/4 | 1/2 | 0/4 | 0/5 |
| PancytopeniaBlood and lymphatic system disorders | 0/1 | 0/3 | 1/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| Acute myocardial infarctionCardiac disorders | 0/1 | 1/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| AscitesGastrointestinal disorders | 0/1 | 0/3 | 0/2 | 0/3 | 1/4 | 0/2 | 0/4 | 0/5 |
| GastroenteritisInfections and infestations | 0/1 | 0/3 | 0/2 | 0/3 | 1/4 | 0/2 | 0/4 | 0/5 |
| Infusion related reactionInjury, poisoning and procedural complications | 0/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 1/4 | 0/5 |
| Peripheral swellingGeneral disorders | 0/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 1/5 |
| PneumoniaInfections and infestations | 0/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 1/5 |
| Acute kidney injuryRenal and urinary disorders | 0/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 1/5 |
| Event | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg |
|---|---|---|---|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/1 | 0/3 | 2/2 | 1/3 | 0/4 | 1/2 | 3/4 | 2/5 |
| NeutropeniaBlood and lymphatic system disorders | 1/1 | 0/3 | 2/2 | 1/3 | 4/4 | 1/2 | 3/4 | 3/5 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/1 | 2/3 | 2/2 | 1/3 | 2/4 | 2/2 | 4/4 | 4/5 |
| NauseaGastrointestinal disorders | 1/1 | 1/3 | 1/2 | 2/3 | 0/4 | 2/2 | 3/4 | 5/5 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 1/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| Musculoskeletal chest painMusculoskeletal and connective tissue disorders | 1/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| FlatulenceGastrointestinal disorders | 1/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| FatigueGeneral disorders | 1/1 | 1/3 | 1/2 | 1/3 | 0/4 | 1/2 | 3/4 | 1/5 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 1/1 | 1/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 0/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/1 | 0/3 | 0/2 | 0/3 | 0/4 | 0/2 | 0/4 | 2/5 |
Intent-to-Treat (ITT) Population: all enrolled participants.
| Age, Continuous(Years) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Mean | 62.5 ± 6.4 | 70.7 ± 15.2 | 55.5 ± 10.6 | 67.3 ± 8.4 | 56.5 ± 12.9 | 52.5 ± 6.4 | 53.3 ± 6.7 | 64.2 ± 9.8 | 60.6 ± 10.8 |
| Sex: Female, Male(Participants) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 1 | 1 | 1 | 1 | 2 | 0 | 2 | 4 | 12 |
| Male | 1 | 2 | 1 | 2 | 2 | 2 | 2 | 1 | 13 |
| Ethnicity (NIH/OMB)(Participants) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Not Hispanic or Latino | 2 | 3 | 2 | 2 | 3 | 2 | 4 | 5 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB)(Participants) | DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg | DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 | DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 | FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg | FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 2 | 0 | 1 | 1 | 2 | 0 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 2 | 3 | 0 | 2 | 3 | 1 | 1 | 5 | 17 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
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Hoffmann-La Roche