A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02729896
Collaborator
(none)
36
19
3
34.9
1.9
0.1
Study Details
Study Description
Brief Summary
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab
- Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
36 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Actual Study Start Date
:
Nov 9, 2016
Actual Primary Completion Date
:
Sep 3, 2018
Actual Study Completion Date
:
Oct 7, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose-Escalation Phase During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, Atezo on Day 1, and Pola on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. |
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.
NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.
Drug: Obinutuzumab
Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).
|
| Experimental: Expansion Phase For FL during the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola at identified RP2D (decided from dose-escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1 and Pola at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months (during maintenance treatment for FL participants). |
Drug: Obinutuzumab
Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).
Drug: Rituximab
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).
|
| Experimental: Safety Run-In Phase For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1. |
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.
NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).
Drug: Rituximab
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)]
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Secondary Outcome Measures
- Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)]
Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
- Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)]
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population
- Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)]
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
- Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone [Baseline up to 35 months]
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
- Percentage of Participants With Adverse Events and Serious Adverse Events [Baseline up to 35 months]
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0.
- Serum Obinutuzumab Concentration [Pre-dose (0 hr) up to 35 months]
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr)
- Serum Rituximab Concentration [Pre-dose (0 hr) up to 35 months]
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr)
- Serum Atezo Concentration [Pre-dose (0 hr) up to 35 months]
pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
- Serum Pola Concentration [Pre-dose (0 hr) up to 35 months]
pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
- Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [Baseline up to 35 months]
Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
- Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab [Baseline to 35 months]
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo [Baseline to 35 months]
Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
- Percentage of Participants With ATAs to Pola [Baseline to 35 months]
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
-
For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
-
For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation
-
Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
-
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
-
For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period for greater than or equal to (>=) 5 months after last dose of Atezo, >= 12 months after last dose of rituximab, >= 12 months after last dose of Pola, and >= 18 months after last dose of obinutuzumab
-
For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of <1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period
Exclusion Criteria:
-
Grade 3b follicular lymphoma
-
History of transformation of indolent disease to DLBCL
-
Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration
-
Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)
-
Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
-
Treatment with systemic immunosuppressive medications, including but not limited to prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1
-
History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
-
Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease
-
Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1
-
Pre-existing Grade greater than (>) 1 neuropathy
-
Major surgical procedure other than for diagnosis within 28 days prior to D1C1
-
Inadequate hematologic function, renal function, and liver function
-
Pregnant or lactating women
-
Life expectancy < 3 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA | Los Angeles | California | United States | 90095 |
| 2 | University Miami | Miami | Florida | United States | 33136 |
| 3 | Stony Brook University Hospital | Stony Brook | New York | United States | 11794 |
| 4 | Columbia Basin Hem-Onc; Department Hematology Oncology | Kennewick | Washington | United States | 99336 |
| 5 | Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology | Morgantown | West Virginia | United States | 26506 |
| 6 | Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin | Dessau-Roßlau | Germany | 06847 | |
| 7 | Uniklinik Essen | Essen | Germany | 45122 | |
| 8 | Universitatsklinikum Frankfurt | Frankfurt | Germany | 60590 | |
| 9 | Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik | Greifswald | Germany | 17475 | |
| 10 | Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie | Hannover | Germany | 30625 | |
| 11 | Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie | Jena | Germany | 07747 | |
| 12 | Klinikum rechts der Isar der Technischen Universität München | Munchen | Germany | 81675 | |
| 13 | Universitätsklinikum Würzburg | Wuerzburg | Germany | 97080 | |
| 14 | Szpitale Wojewodzkie w Gdyni Sp. z o.o. | Gdynia | Poland | 81-519 | |
| 15 | Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego | Lodz | Poland | 9351 | |
| 16 | Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych | Warsaw | Poland | 02-776 | |
| 17 | MTZ Clinical Research Sp. z o.o. | Warszawa | Poland | 02-106 | |
| 18 | Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego | Warszawa | Poland | 02-781 | |
| 19 | Medical Uni of Wroclaw; Hematology | Wroclaw | Poland | 50-367 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02729896
Other Study ID Numbers:
- BO29561
- 2015-004845-25
First Posted:
Apr 6, 2016
Last Update Posted:
Dec 23, 2020
Last Verified:
Nov 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 11 investigational centres in Germany (3), Poland (5) and USA (3). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Period Title: Overall Study | |||
| STARTED | 3 | 10 | 23 |
| COMPLETED | 1 | 1 | 1 |
| NOT COMPLETED | 2 | 9 | 22 |
Baseline Characteristics
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | Total |
|---|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | Total of all reporting groups |
| Overall Participants | 3 | 10 | 23 | 36 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
66.7%
|
6
60%
|
12
52.2%
|
20
55.6%
|
| >=65 years |
1
33.3%
|
4
40%
|
11
47.8%
|
16
44.4%
|
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
52.3
(13.6)
|
57.7
(11.7)
|
64.3
(15.3)
|
61.5
(14.5)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
4
40%
|
9
39.1%
|
13
36.1%
|
| Male |
3
100%
|
6
60%
|
14
60.9%
|
23
63.9%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| Hispanic or Latino |
0
0%
|
1
10%
|
3
13%
|
4
11.1%
|
| Not Hispanic or Latino |
3
100%
|
9
90%
|
18
78.3%
|
30
83.3%
|
| Unknown |
0
0%
|
0
0%
|
2
8.7%
|
2
5.6%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| Unknown |
0
0%
|
1
10%
|
2
8.7%
|
3
8.3%
|
| White |
3
100%
|
9
90%
|
21
91.3%
|
33
91.7%
|
Outcome Measures
| Title | Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan |
|---|---|
| Description | Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Time Frame | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 7 | 16 |
| Number [Percentage of participants] |
33.33
1111%
|
14.30
143%
|
12.50
54.3%
|
| Title | Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone |
|---|---|
| Description | Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Time Frame | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 7 | 16 |
| Number [Percentage of participants] |
0.00
0%
|
57.14
571.4%
|
12.50
54.3%
|
| Title | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans |
|---|---|
| Description | Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population |
| Time Frame | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 7 | 16 |
| Number [Percentage of participants] |
33.33
1111%
|
57.14
571.4%
|
25.00
108.7%
|
| Title | Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone |
|---|---|
| Description | Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Time Frame | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 7 | 16 |
| Number [Percentage of participants] |
33.33
1111%
|
57.14
571.4%
|
25.00
108.7%
|
| Title | Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone |
|---|---|
| Description | Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. |
| Time Frame | Baseline up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 7 | 16 |
| Complete response |
33.3
1110%
|
14.3
143%
|
12.5
54.3%
|
| Partial response |
0
0%
|
42.9
429%
|
12.5
54.3%
|
| Stable disease |
33.3
1110%
|
14.3
143%
|
6.3
27.4%
|
| Progressive disease |
33.3
1110%
|
14.3
143%
|
31.3
136.1%
|
| Not available |
0
0%
|
14.3
143%
|
37.5
163%
|
| Title | Percentage of Participants With Adverse Events and Serious Adverse Events |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0. |
| Time Frame | Baseline up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 | 21 |
| Number [Percentage of participants] |
100.00
3333.3%
|
100.00
1000%
|
81.00
352.2%
|
| Title | Serum Obinutuzumab Concentration |
|---|---|
| Description | pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr) |
| Time Frame | Pre-dose (0 hr) up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg |
|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 |
| Induction cycle 1 Day 1 Pre-dose |
NA
(NA)
|
NA
(NA)
|
| Induction cycle 1 Day 1 Post-dose |
308
(41.6)
|
295
(171)
|
| Induction cycle 2 Day 1 Pre-dose |
351
(81.3)
|
403
(143)
|
| Induction cycle 2 Day 1 Post-dose |
616
(115)
|
672
(130)
|
| Induction cycle 4 Day 1 Pre-dose |
433
(322)
|
311
(177)
|
| Induction cycle 4 Day 1 Post-dose |
583
(189)
|
619
(160)
|
| Induction cycle 6 Day 1 Pre-dose |
288
(123)
|
308
(194)
|
| Induction cycle 6 Day 1 Post-dose |
514
(121)
|
605
(161)
|
| Maintenance Month 1 Day 1 Pre-dose |
221
(NA)
|
171
(131)
|
| Maintenance Month 7 Pre-dose |
90.4
(58.8)
|
83.8
(59.6)
|
| Maintenance Month 13 Pre-dose |
78.8
(42.8)
|
158
(1.41)
|
| Study drug completion or early discontinuation |
37.2
(NA)
|
|
| PK and Immunogenicity follow up |
110
(120)
|
15.4
(3.20)
|
| Title | Serum Rituximab Concentration |
|---|---|
| Description | pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr) |
| Time Frame | Pre-dose (0 hr) up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Safety Run-In Phase |
|---|---|
| Arm/Group Description | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 21 |
| Induction Cycle 1 Day 1 Pre-dose |
30.4
(28.8)
|
| Induction Cycle 1 Day 1 Post-dose |
197
(56.9)
|
| Induction Cycle 2 Day 1 Pre-dose |
43.5
(28.7)
|
| Induction Cycle 4 Day 1 Pre-dose |
84.8
(35.7)
|
| Induction Cycle 6 Day 1 Pre-dose |
101
(45.5)
|
| Induction Cycle 6 Day 1 Post-dose |
239
(42.8)
|
| Title | Serum Atezo Concentration |
|---|---|
| Description | pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min) |
| Time Frame | Pre-dose (0 hr) up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 | 21 |
| Induction Cycle 2 Day 1 Pre-dose |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Induction Cycle 2 Day 1 Post-dose |
332
(56.7)
|
365
(80.7)
|
355
(78.8)
|
| Induction Cycle 3 Day 1 Pre-dose |
86.9
(28.8)
|
78.7
(18.4)
|
79.7
(30.6)
|
| Induction Cycle 4 Day 1 Pre-dose |
139
(33.1)
|
125
(47.3)
|
139
(56.4)
|
| Induction Cycle 4 Day 1 Post-dose |
462
(82.0)
|
450
(136)
|
489
(131)
|
| Induction Cycle 6 Day 1 Pre-dose |
194
(67.7)
|
181
(112)
|
180
(90.6)
|
| Maintenance Month 1 Day 1 Pre-dose |
100
(66.0)
|
70.7
(55.5)
|
|
| Maintenance Month 1 Day 2 Post-dose |
577
(144)
|
473
(177)
|
|
| Maintenance Month 4 Pre-dose |
240
(101)
|
140
(141)
|
|
| Maintenance Month 7 Pre-dose |
226
(134)
|
221
(90.5)
|
|
| Maintenance Month 13 Pre-dose |
106
(83.0)
|
||
| Study drug completion or early discontinuation |
127
(NA)
|
93.0
(14.2)
|
|
| Consolidation Month 1 Day 1 Pre-dose |
132
(43.3)
|
||
| Consolidation Month 1 Day 2 Post-dose |
503
(214)
|
||
| PK and Immunogenicity followup 120D |
61.4
(60.3)
|
16.8
(26.8)
|
19.9
(0.778)
|
| PK and Immunogenicity followup 1 Year |
NA
(NA)
|
| Title | Serum Pola Concentration |
|---|---|
| Description | pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min) |
| Time Frame | Pre-dose (0 hr) up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 | 21 |
| Pre Day 120 Follow-up |
0.136
(NA)
|
2.91
(NA)
|
|
| Induction Cycle 1 Day 1 Pre-dose |
0.847
(NA)
|
35.9
(NA)
|
|
| Induction Cycle 2 Day 1 Pre-dose |
2.54
(0.918)
|
2.62
(1.22)
|
3.37
(3.60)
|
| Induction Cycle 4 Day 1 Pre-dose |
4.73
(2.10)
|
4.27
(1.63)
|
4.92
(2.65)
|
| Maintenance Month 1 Day 1 Pre-dose |
1.30
(0.696)
|
1.63
(1.75)
|
|
| Study drug completion or early discontinuation |
0.716
(0.200)
|
| Title | Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab |
|---|---|
| Description | Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr) |
| Time Frame | Baseline up to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg |
|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 |
| Number [Percentage of participants] |
0
0%
|
0
0%
|
| Title | Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab |
|---|---|
| Description | Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr) |
| Time Frame | Baseline to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. (FL cohorts not applicable as rituximab was only administered in the Safety Run- in phase). |
| Arm/Group Title | Safety Run-In Phase |
|---|---|
| Arm/Group Description | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 21 |
| Baseline, positive |
5.6
186.7%
|
| Baseline, negative |
94.4
3146.7%
|
| Induction Cycle 2 Day 1, positive |
5.6
186.7%
|
| Induction Cycle 2 Day 1, negative |
94.4
3146.7%
|
| Induction Cycle 4 Day 1 |
100
3333.3%
|
| Induction Cycle 6 Day 1 |
100
3333.3%
|
| Study drug completion |
100
3333.3%
|
| Title | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo |
|---|---|
| Description | Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min) |
| Time Frame | Baseline to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population for this outcome measure includes participants in the DLBCL cohort who received at least one dose of any study treatment. Participants in the FL 1.4 mg and FL 1.8 mg were not anazlyed. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 | 21 |
| Induction, Cycle 2 Day 1, positive |
0
0%
|
0
0%
|
5.3
23%
|
| Induction, Cycle 2 Day 1, negative |
0
0%
|
0
0%
|
94.7
411.7%
|
| Induction, Cycle 3 Day 1, positive |
0
0%
|
0
0%
|
7.1
30.9%
|
| Induction, Cycle 3 Day 1, negative |
0
0%
|
0
0%
|
92.9
403.9%
|
| Induction, Cycle 4 Day 1, negative |
0
0%
|
0
0%
|
100.0
434.8%
|
| Induction, Cycle 6 Day 1, negative |
0
0%
|
0
0%
|
100.0
434.8%
|
| Consolidation Month 1 Day 1, negative |
0
0%
|
0
0%
|
100.0
434.8%
|
| Study drug completion, negative |
0
0%
|
0
0%
|
100.0
434.8%
|
| Atezo PK Immunogenicity Follow up (120D), negative |
0
0%
|
0
0%
|
100.0
434.8%
|
| Title | Percentage of Participants With ATAs to Pola |
|---|---|
| Description | Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min) |
| Time Frame | Baseline to 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Evaluable Population that includes patients who received at least one dose of any study treatment. |
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-In Phase |
|---|---|---|---|
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. |
| Measure Participants | 3 | 10 | 21 |
| Number [Percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From randomization up to 35 months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All adverse events that occurred on or after the first dose of study treatment are summarized by mapped term, appropriate thesaurus levels, and National Cancer Institute Common Terminology Criteria (NCI CTCAE) v4.0 grade. All-Cause Mortality is reported for the ITT population. | |||||
| Arm/Group Title | Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | |||
| Arm/Group Description | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 milligram (mg) of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and 1.4 mg/kilogram (kg) of pola on Day 1. The 1.4 mg/kg dose was cleared by an Internal Monitoring Committee (IMC) review and escalated to 1.8 mg/kg. This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. | During the induction treatment Cycle 1 (21-day cycles): participants received obinutuzumab on Days 1, 8, and 15 and pola on Day 1; Cycles 2-6: participants received 1000 mg of obinutuzumab on Day 1, 1200 mg of atezo on Day 1, and pola was escalated to 1.8 mg/kg (on Day 1); once cleared by the IMC it was declared as the recommended phase 2 dose (RP2D). This was followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants received a 375 mg/m^2 IV of rituximab on Day 1 and on Day 1 of every other month during consolidation. Participants also received a 1.8 mg/kg IV of Pola on Day 1. Cycles 2-6: participants received 1200 mg of Atezo on Day 1. Due to unexpected toxicity, recruitment was stopped, and atezolizumab discontinued in all treated patients. This combination will not be further developed. | |||
All Cause Mortality |
||||||
| Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 2/10 (20%) | 13/23 (56.5%) | |||
Serious Adverse Events |
||||||
| Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 4/10 (40%) | 2/21 (9.5%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| FEBRILE NEUTROPENIA | 0/3 (0%) | 0 | 2/10 (20%) | 2 | 0/21 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/21 (4.8%) | 1 |
| STOMATITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| General disorders | ||||||
| DEATH | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| PYREXIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Infections and infestations | ||||||
| BRONCHOPULMONARY ASPERGILLOSIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| ERYSIPELAS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| SEPSIS | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/21 (4.8%) | 1 |
| Investigations | ||||||
| C-REACTIVE PROTEIN INCREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Nervous system disorders | ||||||
| GUILLAIN-BARRE SYNDROME | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| LETHARGY | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/21 (4.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| PLEURAL EFFUSION | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 1/21 (4.8%) | 1 |
| PNEUMONITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| DERMATITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| ERYTHEMA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Dose-Escalation FL Cohort 1.4 mg | Dose-Escalation and Expansion FL Cohort 1.8 mg | Safety Run-in and Expansion DLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 10/10 (100%) | 15/21 (71.4%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 2/21 (9.5%) | 2 |
| ANAEMIA FOLATE DEFICIENCY | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| LEUKOPENIA | 0/3 (0%) | 0 | 2/10 (20%) | 5 | 1/21 (4.8%) | 1 |
| NEUTROPENIA | 1/3 (33.3%) | 1 | 4/10 (40%) | 7 | 3/21 (14.3%) | 4 |
| THROMBOCYTOPENIA | 0/3 (0%) | 0 | 4/10 (40%) | 5 | 0/21 (0%) | 0 |
| Cardiac disorders | ||||||
| SINUS TACHYCARDIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Endocrine disorders | ||||||
| AUTOIMMUNE THYROIDITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| HYPOTHYROIDISM | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Eye disorders | ||||||
| DRY EYE | 0/3 (0%) | 0 | 2/10 (20%) | 2 | 1/21 (4.8%) | 1 |
| GLAUCOMA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| SCLERITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| CATARACT NUCLEAR | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| VITREOUS DEGENERATION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 1/21 (4.8%) | 1 |
| CONSTIPATION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| DIARRHOEA | 0/3 (0%) | 0 | 3/10 (30%) | 3 | 0/21 (0%) | 0 |
| DRY MOUTH | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| DYSPEPSIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| STOMATITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| VOMITING | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| General disorders | ||||||
| CHEST PAIN | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| FACE OEDEMA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| FATIGUE | 2/3 (66.7%) | 2 | 3/10 (30%) | 3 | 1/21 (4.8%) | 1 |
| INFLUENZA LIKE ILLNESS | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| INFUSION SITE EXTRAVASATION | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| OEDEMA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| OEDEMA PERIPHERAL | 0/3 (0%) | 0 | 3/10 (30%) | 3 | 5/21 (23.8%) | 5 |
| PERIPHERAL SWELLING | 0/3 (0%) | 0 | 1/10 (10%) | 3 | 1/21 (4.8%) | 1 |
| PYREXIA | 0/3 (0%) | 0 | 4/10 (40%) | 6 | 0/21 (0%) | 0 |
| Infections and infestations | ||||||
| BACTERAEMIA | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| BACTERIAL INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| BRONCHOPULMONARY ASPERGILLOSIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| CONJUNCTIVITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| CYTOMEGALOVIRUS INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| LARYNGITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| NASOPHARYNGITIS | 1/3 (33.3%) | 2 | 2/10 (20%) | 2 | 0/21 (0%) | 0 |
| ORAL FUNGAL INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| PELVIC ABSCESS | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| PNEUMONIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| RHINITIS | 1/3 (33.3%) | 4 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| SINUSITIS | 2/3 (66.7%) | 2 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 3/21 (14.3%) | 3 |
| URINARY TRACT INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| VIRAL INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| VIRAL UPPER RESPIRATORY TRACT INFECTION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| ACUTE SINUSITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| CONJUNCTIVITIS VIRAL | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| INFUSION RELATED REACTION | 1/3 (33.3%) | 1 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Investigations | ||||||
| ALANINE AMINOTRANSFERASE INCREASED | 1/3 (33.3%) | 1 | 2/10 (20%) | 2 | 0/21 (0%) | 0 |
| BLOOD CREATININE INCREASED | 0/3 (0%) | 0 | 2/10 (20%) | 2 | 0/21 (0%) | 0 |
| BLOOD LACTATE DEHYDROGENASE INCREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| C-REACTIVE PROTEIN INCREASED | 0/3 (0%) | 0 | 2/10 (20%) | 5 | 0/21 (0%) | 0 |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| LIPASE INCREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| NEUTROPHIL COUNT DECREASED | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| PROCALCITONIN INCREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| THYROXINE DECREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| TRI-IODOTHYRONINE DECREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| WEIGHT DECREASED | 0/3 (0%) | 0 | 4/10 (40%) | 4 | 0/21 (0%) | 0 |
| WHITE BLOOD CELL COUNT DECREASED | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| DECREASED APPETITE | 0/3 (0%) | 0 | 3/10 (30%) | 3 | 1/21 (4.8%) | 1 |
| FLUID RETENTION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| HYPERGLYCAEMIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| HYPOALBUMINAEMIA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| HYPOKALAEMIA | 0/3 (0%) | 0 | 3/10 (30%) | 3 | 1/21 (4.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHRALGIA | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 2/21 (9.5%) | 2 |
| BACK PAIN | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| BONE PAIN | 1/3 (33.3%) | 1 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| SACROILIITIS | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| TENDONITIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| BASAL CELL CARCINOMA | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| Nervous system disorders | ||||||
| DIZZINESS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 2/21 (9.5%) | 2 |
| FACIAL PARALYSIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| HEADACHE | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 1/21 (4.8%) | 1 |
| HYPOAESTHESIA | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 1/21 (4.8%) | 1 |
| NEUROPATHY PERIPHERAL | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| PARAESTHESIA | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| POLYNEUROPATHY | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Psychiatric disorders | ||||||
| DEPRESSION | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 1/21 (4.8%) | 1 |
| INSOMNIA | 1/3 (33.3%) | 1 | 0/10 (0%) | 0 | 0/21 (0%) | 0 |
| ANXIETY | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 1/21 (4.8%) | 1 |
| Renal and urinary disorders | ||||||
| ACUTE KIDNEY INJURY | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 2/21 (9.5%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| COUGH | 0/3 (0%) | 0 | 2/10 (20%) | 3 | 2/21 (9.5%) | 3 |
| DYSPNOEA | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 2/21 (9.5%) | 2 |
| DYSPNOEA EXERTIONAL | 0/3 (0%) | 0 | 0/10 (0%) | 0 | 2/21 (9.5%) | 2 |
| HICCUPS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| LARYNGEAL OEDEMA | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| PULMONARY EMBOLISM | 0/3 (0%) | 0 | 1/10 (10%) | 2 | 0/21 (0%) | 0 |
| PULMONARY THROMBOSIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| NIGHT SWEATS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| RASH | 0/3 (0%) | 0 | 1/10 (10%) | 4 | 0/21 (0%) | 0 |
| Vascular disorders | ||||||
| HYPERTENSION | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
| THROMBOSIS | 0/3 (0%) | 0 | 1/10 (10%) | 1 | 0/21 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800 821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02729896
Other Study ID Numbers:
- BO29561
- 2015-004845-25
First Posted:
Apr 6, 2016
Last Update Posted:
Dec 23, 2020
Last Verified:
Nov 1, 2020