Lymphoma, Follicular
Conditions
Brief summary
This study will evaluate the safety, efficacy, pharmacokinetics and immunogenicity of induction treatment consisting of atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma (FL), followed by maintenance treatment with atezolizumab plus obinutzumab plus lenalidomide in patients who achieve a complete response (CR), a partial response (PR), or stable disease at end of induction.
Interventions
DRUGAtezolizumab (MPDL3280A) [TECENTRIQ]
Atezolizumab will be administered at a flat dose of 840 mg on Days 1 and 15 of Cycles 2 to 6, given in 28-day cycles as induction treatment and 840 mg on Days 1 and 2 of each month, given as maintenance treatment.
DRUGLenalidomide
Lenalidomide will be administered orally once daily on Days 1 to 21 of Cycles 1 to 6 (28-day cycles) during induction treatment and on Days 1 to 21 of each month during maintenance treatment. Lenalidomide will be administered at a dose of 15 or 20 mg (dose may be de-escalated to 10 mg) during induction treatment and at 10 mg during maintenance treatment. During the expansion phase, lenalidomide will be administered at the RP2D during induction treatment and at 10 mg during maintenance treatment.
DRUGObinutuzumab
Obinutuzumab will be administered by intravenous infusion at an absolute (flat) dose of 1000 mg on Days 1, 8, and 15 of the first cycle and on Day 1 of each subsequent cycle during induction treatment, and on Day 1 of every other month (i.e., every 2 months) during maintenance treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator * Histologically documented CD20-positive lymphoma as determined by the local laboratory * Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma) * At least one bi-dimensionally measurable lesion (\>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging \[MRI\]) * Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL * Agreement to comply with all local requirements of the lenalidomide risk minimization plan * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \<1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 18 months after the last dose of study treatment * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm for at least 3 months after the last dose of study treatment
Exclusion criteria
* Grade 3b follicular lymphoma * History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL) * Known CD20-negative status at relapse or progression * Central nervous system lymphoma or leptomeningeal infiltration * Prior allogeneic stem-cell transplantation (SCT) * Completion of autologous SCT within 100 days prior to Day (D) 1 of Cycle (C) 1 * Prior standard or investigational anti-cancer therapy as specified in protocol * History of resistance to lenalidomide or response duration of \<1 year * Treatment with systemic immunosuppressive medications * History of solid organ transplantation * Clinically significant toxicity from prior therapy that has not resolved to Grade \<=2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\], v4.0) prior to Day 1 of Cycle 1 * History of erythema multiforme, Grade \>= 3 rash, or blistering following prior treatment with immunomodulatory derivatives such as thalidomide and lenalidomide * Active bacterial, viral, fungal, or other infection * Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening * Known history of HIV positive status * History of progressive multifocal leukoencephalopathy * History of autoimmune disease * Contraindication to treatment for TE prophylaxis * Grade \<= 2 neuropathy * History of other malignancy that could affect compliance with the protocol or interpretation of results * Evidence of any significant, uncontrolled concomitant disease * Inadequate hematologic function (unless due to underlying lymphoma) * Abnormal laboratory values (unless due to underlying lymphoma) * Pregnant or lactating or intending to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria | 6 months (up to clinical cut-off date (CCOD) of 23 October 2018) | Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria | 6 months (up to CCOD of 23 October 2018) | CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator. |
| Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans | 6 months (up to CCOD of 23 October 2018) | Objective response was evaluated through use of PET-CT scans, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator. |
| Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone | 6 months (up to CCOD of 23 October 2018) | Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator. |
| Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone | 30 months | Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator. |
| Percentage of Participants With Adverse Events and Serious Adverse Events | Baseline up to approximately 59 months | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria | 6 months (up to CCOD of 23 October 2018) | CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator. |
| Serum Concentration of Obinutuzumab (mcg/mL) | Baseline up to approximately 59 months | The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year |
| Serum Concentration of Atezolizumab (mcg/mL) | Baseline up to approximately 59 months | The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year |
| Serum Concentration of Lenalidomide (ng/mL) | Baseline up to approximately 59 months | The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour |
| Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Baseline up to approximately 59 months | The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below. |
| Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Baseline up to approximately 59 months | The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below. |
| Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment | Day 1 - Day 28 of second cycle | Does limiting toxicity (DLT) is defined as any one of the following events occurring during Cycle 2 of treatment and assessed by the investigator as related to study treatment: - Adverse event of any grade that leads to a delay of more than 14 days at the start of the next treatment cycle; - Hematologic adverse events (neutropenia, thrombocytopenia); - Non-hematologic adverse event, except IRRs, diarrhea, nausea or vomiting |
Countries
France, United States
Participant flow
Recruitment details
The study was conducted at 14 sites in France (9) and USA (5).
Pre-assignment details
All participants received daily low-dose aspirin (81-100 mg) during lenalidomide treatment and until 28 days after the last dose of lenalidomide. Participants who are unable to tolerate aspirin, who have a history of thromboembolism (TE), and who are at high risk of TE, received warfarin or low-molecular-weight heparin (LMWH).
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab-G-lena 15mg Participants were administered obinutuzumab, atezolizumab, and 15 mg of lenalidomide | 4 |
| Atezolizumab-G-lena 20mg Participants were administered obinutuzumab, atezolizumab, and 20 mg of lenalidomide. | 34 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 7 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Atezolizumab-G-lena 20mg | Total | Atezolizumab-G-lena 15mg |
|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 9.7 | 60.0 Years STANDARD_DEVIATION 9.6 | 56.5 Years STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 13 Participants | 16 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Stated | 12 Participants | 12 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 20 Participants | 9 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 18 Participants | 4 Participants |
| Sex: Female, Male Female | 18 Participants | 19 Participants | 1 Participants |
| Sex: Female, Male Male | 16 Participants | 19 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 7 / 34 |
| other Total, other adverse events | 4 / 4 | 34 / 34 |
| serious Total, serious adverse events | 2 / 4 | 16 / 34 |
Outcome results
Primary
Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria
Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC.
Time frame: 6 months (up to clinical cut-off date (CCOD) of 23 October 2018)
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria | 71.9 Percentage of Participants |
Secondary
Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below.
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C2 D15 - Negative | 2 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M7 - Negative | 2 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C6 D1 - Negative | 3 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M13 - Negative | 1 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C2 D1 - Negative | 4 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M19 - Negative | 2 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M1 - Negative | 3 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Study drug completion or early discontinuation - Negative | 2 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C4 D1 - Negative | 3 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | ATEZO, PK, IMMUNO FU 120D - Negative | 1 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M4 - Negative | 3 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | ATEZO, PK, IMMUNO FU 1YR - Negative | 2 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M4 - Negative | 25 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C2 D1 - Negative | 31 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C2 D15 - Negative | 32 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C4 D1 - Negative | 29 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Ind C6 D1 - Negative | 28 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M1 - Negative | 27 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | ATEZO, PK, IMMUNO FU 1YR - Negative | 3 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M7 - Negative | 21 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M13 - Negative | 20 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Maint M19 - Negative | 12 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | Study drug completion or early discontinuation - Negative | 15 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab | ATEZO, PK, IMMUNO FU 120D - Negative | 11 Participants |
Secondary
Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below.
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Ind C6 D1 - Negative | 3 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Baseline - Negative | 4 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Study drug completion or early discontinuation - Negative | 0 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | OB, PK, IMMUNO FU 120D - Negative | 1 Participants |
| Atezolizumab-G-lena 15mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | OB, PK, IMMUNO FU 1YR - Negative | 2 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | OB, PK, IMMUNO FU 120D - Negative | 11 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Study drug completion or early discontinuation - Negative | 15 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | OB, PK, IMMUNO FU 1YR - Negative | 4 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Baseline - Negative | 34 Participants |
| Atezolizumab-G-lena 20mg | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab | Ind C6 D1 - Negative | 27 Participants |
Secondary
Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment
Does limiting toxicity (DLT) is defined as any one of the following events occurring during Cycle 2 of treatment and assessed by the investigator as related to study treatment: - Adverse event of any grade that leads to a delay of more than 14 days at the start of the next treatment cycle; - Hematologic adverse events (neutropenia, thrombocytopenia); - Non-hematologic adverse event, except IRRs, diarrhea, nausea or vomiting
Time frame: Day 1 - Day 28 of second cycle
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab-G-lena 15mg | Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment | 0 Number of Participants |
| Atezolizumab-G-lena 20mg | Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment | 0 Number of Participants |
Secondary
Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria
CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator.
Time frame: 6 months (up to CCOD of 23 October 2018)
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria | 75 Percentage of Participants |
Secondary
Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria
CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Time frame: 6 months (up to CCOD of 23 October 2018)
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria | Determined by the IRC with CT or MRI | 31.3 Percentage of Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria | Determined by Investigator with CT or MRI | 50 Percentage of Participants |
Secondary
Percentage of Participants With Adverse Events and Serious Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab-G-lena 15mg | Percentage of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 4 Participants |
| Atezolizumab-G-lena 15mg | Percentage of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 2 Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 34 Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 16 Participants |
Secondary
Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone
Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator.
Time frame: 30 months
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone | Best Response (CR,PR) | 87.5 Percentage |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone | CR | 68.8 Percentage |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone | PR | 18.8 Percentage |
Secondary
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone
Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator.
Time frame: 6 months (up to CCOD of 23 October 2018)
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone | Determined by IRC, based on Lugano 2014 - CT | 81.3 Percentage of Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone | Determined by Inv., based on Lugano 2014 - CT | 87.5 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans
Objective response was evaluated through use of PET-CT scans, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Time frame: 6 months (up to CCOD of 23 October 2018)
Population: As no DLTs were observed, the dose of 20 mg lenalidomide was confirmed as the recommended Phase II dose (RP2D) for lenalidomide. Only participants who received lenalidomide induction at the 20 mg RP2D were included in the Efficacy Evaluable population, hence participants in the Atezo-G-L 15 mg arm were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans | Determined by IRC, based on Lugano 2014 - PET | 81.3 Percentage of Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans | Determined by Inv., based on Lugano 2014 - PET | 84.4 Percentage of Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans | Determined by IRC, Modified Lugano 2014 - PET-CT | 78.1 Percentage of Participants |
| Atezolizumab-G-lena 20mg | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans | Determined by Inv, Modified Lugano 2014 - PET-CT | 84.4 Percentage of Participants |
Secondary
Serum Concentration of Atezolizumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C4 D1 - 30 min. Postdose | 340 micrograms per milliliter (mcg/mL) | Standard Deviation 38.2 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M4 - Predose | 174 micrograms per milliliter (mcg/mL) | Standard Deviation 32.9 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C2 D1 - 30 min. Postdose | 345 micrograms per milliliter (mcg/mL) | Standard Deviation 195 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M7 - Predose | 209 micrograms per milliliter (mcg/mL) | Standard Deviation 12.7 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C6 D1 - Predose | 194 micrograms per milliliter (mcg/mL) | Standard Deviation 40.6 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M13 - Predose | 203 micrograms per milliliter (mcg/mL) | — |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C4 D1 - Predose | 128 micrograms per milliliter (mcg/mL) | Standard Deviation 33.9 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M19 - Predose | 351 micrograms per milliliter (mcg/mL) | — |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M1 - Predose | 79.0 micrograms per milliliter (mcg/mL) | Standard Deviation 67.6 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C2 D15 - Predose | 73.8 micrograms per milliliter (mcg/mL) | Standard Deviation 6.47 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | PK FU 120D | 46.0 micrograms per milliliter (mcg/mL) | — |
| Atezolizumab-G-lena 15mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M1 - Day 2, 30 min. Postdose | 653 micrograms per milliliter (mcg/mL) | Standard Deviation 106 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | TRTC | 116 micrograms per milliliter (mcg/mL) | Standard Deviation 81.9 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C2 D1 - Predose | 0.184 micrograms per milliliter (mcg/mL) | — |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | PK FU 120D | 38.4 micrograms per milliliter (mcg/mL) | Standard Deviation 24.6 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C2 D1 - 30 min. Postdose | 279 micrograms per milliliter (mcg/mL) | Standard Deviation 123 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C2 D15 - Predose | 90.0 micrograms per milliliter (mcg/mL) | Standard Deviation 33.8 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C4 D1 - Predose | 226 micrograms per milliliter (mcg/mL) | Standard Deviation 93.9 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C4 D1 - 30 min. Postdose | 477 micrograms per milliliter (mcg/mL) | Standard Deviation 126 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Ind C6 D1 - Predose | 279 micrograms per milliliter (mcg/mL) | Standard Deviation 117 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M1 - Predose | 172 micrograms per milliliter (mcg/mL) | Standard Deviation 76.5 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M1 - Day 2, 30 min. Postdose | 666 micrograms per milliliter (mcg/mL) | Standard Deviation 185 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M4 - Predose | 292 micrograms per milliliter (mcg/mL) | Standard Deviation 97.1 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M7 - Predose | 322 micrograms per milliliter (mcg/mL) | Standard Deviation 109 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M13 - Predose | 309 micrograms per milliliter (mcg/mL) | Standard Deviation 140 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Atezolizumab (mcg/mL) | Maint M19 - Predose | 327 micrograms per milliliter (mcg/mL) | Standard Deviation 140 |
Secondary
Serum Concentration of Lenalidomide (ng/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - Predose | 3.57 nanograms/milliliter (ng/mL) | Standard Deviation 3.25 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 2.0 hr. Postdose | 146 nanograms/milliliter (ng/mL) | Standard Deviation 41.9 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C1 D15 - 2.0 hr. Postdose | 254 nanograms/milliliter (ng/mL) | Standard Deviation 115 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 4.0 hr. Postdose | 95.8 nanograms/milliliter (ng/mL) | Standard Deviation 18.3 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 30 min. Postdose | 241 nanograms/milliliter (ng/mL) | Standard Deviation 116 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 8.0 hr. Postdose | 45.9 nanograms/milliliter (ng/mL) | Standard Deviation 23.9 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C1 D15 - Predose | 12.6 nanograms/milliliter (ng/mL) | Standard Deviation 14.3 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C6 D15 - Predose | 5.72 nanograms/milliliter (ng/mL) | Standard Deviation 3.73 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 -1.0 hr. Postdose | 224 nanograms/milliliter (ng/mL) | Standard Deviation 43.1 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C6 D15 - 2.0 hr. Postdose | 200 nanograms/milliliter (ng/mL) | Standard Deviation 57.5 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C6 D15 - 2.0 hr. Postdose | 214 nanograms/milliliter (ng/mL) | Standard Deviation 77.6 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C1 D15 - Predose | 13.0 nanograms/milliliter (ng/mL) | Standard Deviation 11.4 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C1 D15 - 2.0 hr. Postdose | 294 nanograms/milliliter (ng/mL) | Standard Deviation 114 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - Predose | 15.0 nanograms/milliliter (ng/mL) | Standard Deviation 13 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 30 min. Postdose | 293 nanograms/milliliter (ng/mL) | Standard Deviation 233 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 -1.0 hr. Postdose | 354 nanograms/milliliter (ng/mL) | Standard Deviation 120 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 2.0 hr. Postdose | 262 nanograms/milliliter (ng/mL) | Standard Deviation 82.1 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 4.0 hr. Postdose | 150 nanograms/milliliter (ng/mL) | Standard Deviation 47.1 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C2 D15 - 8.0 hr. Postdose | 68.4 nanograms/milliliter (ng/mL) | Standard Deviation 33.6 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Lenalidomide (ng/mL) | Ind C6 D15 - Predose | 9.17 nanograms/milliliter (ng/mL) | Standard Deviation 6.87 |
| Unknown | Serum Concentration of Lenalidomide (ng/mL) | Ind C1 D1 - Predose | — nanograms/milliliter (ng/mL) | — |
Secondary
Serum Concentration of Obinutuzumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year
Time frame: Baseline up to approximately 59 months
Population: The Safety Evaluable Population included participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M1 - Predose | 114 mcg/mL | Standard Deviation 16.7 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C1 D1 - 30 min. Postdose | 364 mcg/mL | Standard Deviation 45.9 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M7 - Predose | 66.1 mcg/mL | Standard Deviation 20.4 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C4 D1 - 30 min. Postdose | 509 mcg/mL | Standard Deviation 47 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M13 - Predose | 77.9 mcg/mL | — |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C2 D1 - 30 min. Postdose | 606 mcg/mL | Standard Deviation 62.4 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M19 - Predose | 94.0 mcg/mL | Standard Deviation 24 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C6 D1 - Predose | 230 mcg/mL | Standard Deviation 12.3 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C2 D1 - Predose | 288 mcg/mL | Standard Deviation 84.2 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | OD120FU | 23.3 mcg/mL | — |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C6 D1 - 30 min. Postdose | 503 mcg/mL | Standard Deviation 25.5 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | O1YFU | 46.9 mcg/mL | Standard Deviation 66.2 |
| Atezolizumab-G-lena 15mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C4 D1 - Predose | 175 mcg/mL | Standard Deviation 38.5 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | OD120FU | 46.2 mcg/mL | Standard Deviation 38.6 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C1 D1 - Predose | 0.634 mcg/mL | Standard Deviation 0.857 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | O1YFU | 57.9 mcg/mL | Standard Deviation 115 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C1 D1 - 30 min. Postdose | 375 mcg/mL | Standard Deviation 163 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C2 D1 - Predose | 392 mcg/mL | Standard Deviation 164 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C2 D1 - 30 min. Postdose | 753 mcg/mL | Standard Deviation 225 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C4 D1 - Predose | 301 mcg/mL | Standard Deviation 150 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C4 D1 - 30 min. Postdose | 657 mcg/mL | Standard Deviation 198 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C6 D1 - Predose | 272 mcg/mL | Standard Deviation 106 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Ind C6 D1 - 30 min. Postdose | 652 mcg/mL | Standard Deviation 177 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M1 - Predose | 201 mcg/mL | Standard Deviation 104 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M7 - Predose | 112 mcg/mL | Standard Deviation 52.1 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M13 - Predose | 104 mcg/mL | Standard Deviation 62.9 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | Maint M19 - Predose | 111 mcg/mL | Standard Deviation 49.8 |
| Atezolizumab-G-lena 20mg | Serum Concentration of Obinutuzumab (mcg/mL) | TRTC | 148 mcg/mL | Standard Deviation 103 |