Lymphoma, Non Hodgkin
Conditions
Brief summary
This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.
Interventions
DRUGCyclophosphamide
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m\^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
DRUGDoxorubicin
Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
DRUGObinutuzumab
Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
DRUGPolatuzumab Vedotin
Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
DRUGPrednisolone
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
DRUGPrednisone
Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
DRUGRituximab
Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Sponsors
Genentech, Inc.
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
All Participants: * At least one bi-dimensionally measurable lesion, defined as greater than (\>) 1.5 centimeters (cm) in its longest dimension * Life expectancy of at least 24 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) * Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of \<1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 5 months after the last dose of study drug Dose-Escalation Portion of the Study: * Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible * No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation \[CD\] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen) * No prior treatment with anthracyclines Expansion Portion of the Study: * Previously untreated participants with diffuse large B-cell lymphoma (DLBCL) * International Prognostic Index (IPI) score of 2-5
Exclusion criteria
Dose-Escalation Portion of the Study: * Diagnosis of primary mediastinal DLBCL Expansion Portion of the Study: * Participants with transformed lymphoma * Prior therapy for NHL All Participants: * Prior stem cell transplant * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products * Contraindication to receive any of the individual components of R-CHP or G-CHP * Current Grade greater than (\>) 1 peripheral neuropathy * Ongoing corticosteroid use of \>30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (\</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1 * Primary central nervous system (CNS) lymphoma * Vaccination with live vaccines within 6 months before Cycle 1 Day 1 * History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (\</=) 5 years before enrollment * Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm) * Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1 * Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis * Positive for hepatitis B or hepatitis C infection * Prior radiotherapy to the mediastinal/pericardial region * Pregnant or lactating women * Recent major surgery within 6 weeks before the start of Cycle 1 Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | Baseline up to 5 years | 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. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs). |
| Number of Participants With Adverse Events in Non-DLBCL Population | Baseline up to 5 years | 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. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs). |
| Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) | All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD. |
| Number of Participants With DLTs in Non-DLBCL Population | Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) | All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) | AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
| Maximum Concentration (Cmax) of Polatuzumab Vedotin | Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) | Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
| Clearance (CL) of Polatuzumab Vedotin | Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) | CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
| Terminal Half-Life (t1/2) of Polatuzumab Vedotin | Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) | t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
| Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) | Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
| Plasma Levels of Cyclophosphamide | End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days) | Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin. |
| Plasma Levels of Doxorubicin | 2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days) | Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin. |
| Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected. | The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment). |
| Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected. | The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment). |
| Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | At the end of treatment (Month 6) | Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET. |
| Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment. |
| Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1. |
| Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1. |
| Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization. |
| Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization. |
| Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 6 months | Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage. |
| Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 6 months | Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage. |
| Overall Survival for DLBCL Population | Screening up to death due to any cause (up to approximately 6 years) | The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive. |
| Overall Survival for Non-DLBCL Population | Screening up to death due to any cause (up to approximately 6 years) | The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive. |
| Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) | Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment. |
| Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | At the end of treatment (Month 6) | Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET. |
| Number of Participants With Anti-Polatuzumab Vedotin Antibodies | Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days) | The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 μg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 μg/mL. Polatuzumab vedotin total antibody concentrations ranged from \<0.050 μg/mL to 52.1 μg/mL with a median concentration of 3.38 μg/mL. |
| Number of Participants With Anti-Obinutuzumab Antibodies | Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days) | The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA. |
Countries
France, United States
Participant flow
Recruitment details
The study was conducted at 11 centers in 2 countries.
Pre-assignment details
A total of 85 participants were enrolled at 11 centers in the following countries: France (31 participants) and United States (54 participants). 3 participants did not receive any study treatment (2 had exclusionary lab values and 1 withdrew) meaning that the safety population consisted of 82 participants.
Participants by arm
| Arm | Count |
|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. | 3 |
| Polatuzumab Vedotin (1.4mg) + R-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. | 3 |
| Polatuzumab Vedotin (1.8mg) + R-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. | 6 |
| Polatuzumab Vedotin (2.4mg) + R-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. | 1 |
| Polatuzumab Vedotin (1.4mg) + G-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. | 6 |
| Polatuzumab Vedotin (1.8mg) + G-CHP Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. | 6 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. | 40 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts. | 17 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 | 1 | 0 | 4 | 2 |
| Overall Study | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Polatuzumab Vedotin (1.8mg) + R-CHP | Polatuzumab Vedotin (1.4mg) + R-CHP | Polatuzumab Vedotin (2.4mg) + R-CHP | Polatuzumab Vedotin (1.4mg) + G-CHP | Polatuzumab Vedotin (1.8mg) + G-CHP | Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Total | Polatuzumab Vedotin (1.0mg) + R-CHP |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 67.3 Years STANDARD_DEVIATION 3.5 | 65.0 Years STANDARD_DEVIATION 7 | 68.0 Years | 70.7 Years STANDARD_DEVIATION 4.5 | 60.0 Years STANDARD_DEVIATION 14.3 | 69.6 Years STANDARD_DEVIATION 7.2 | 61.6 Years STANDARD_DEVIATION 14.6 | 66.9 Years STANDARD_DEVIATION 9.9 | 67.3 Years STANDARD_DEVIATION 6.4 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants | 3 Participants | 1 Participants | 6 Participants | 6 Participants | 27 Participants | 14 Participants | 66 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Stated | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 3 Participants | 12 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 3 Participants | 1 Participants | 5 Participants | 6 Participants | 33 Participants | 15 Participants | 72 Participants | 3 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 4 Participants | 20 Participants | 6 Participants | 39 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants | 20 Participants | 11 Participants | 43 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 1 / 6 | 0 / 1 | 1 / 6 | 0 / 6 | 4 / 40 | 2 / 17 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 1 / 1 | 6 / 6 | 6 / 6 | 40 / 40 | 17 / 17 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 4 / 6 | 0 / 1 | 1 / 6 | 3 / 6 | 15 / 40 | 6 / 17 |
Outcome results
Primary
Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population
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. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Time frame: Baseline up to 5 years
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 2 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 3 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 5 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 4 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 4 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 40 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population | 17 Participants |
Primary
Number of Participants With Adverse Events in Non-DLBCL Population
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. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Time frame: Baseline up to 5 years
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 1 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 1 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 1 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 2 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 2 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Adverse Events in Non-DLBCL Population | 0 Participants |
Primary
Number of Participants With DLTs in Non-DLBCL Population
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Time frame: Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With DLTs in Non-DLBCL Population | 0 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Time frame: Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 1 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 1 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population | 0 Participants |
Secondary
Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin
AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1300 ng day/mL | Standard Deviation 22 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1510 ng day/mL | Standard Deviation 354 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 2600 ng day/mL | Standard Deviation 413 |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 4090 ng day/mL | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1940 ng day/mL | Standard Deviation 154 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1850 ng day/mL | Standard Deviation 491 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1870 ng day/mL | Standard Deviation 527 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin | 1940 ng day/mL | Standard Deviation 482 |
Secondary
Clearance (CL) of Polatuzumab Vedotin
CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Clearance (CL) of Polatuzumab Vedotin | 14.0 mL/day/kg | Standard Deviation 0.37 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Clearance (CL) of Polatuzumab Vedotin | 17.3 mL/day/kg | Standard Deviation 4.16 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Clearance (CL) of Polatuzumab Vedotin | 12.8 mL/day/kg | Standard Deviation 2.05 |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Clearance (CL) of Polatuzumab Vedotin | 10.5 mL/day/kg | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Clearance (CL) of Polatuzumab Vedotin | 13.2 mL/day/kg | Standard Deviation 1.29 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Clearance (CL) of Polatuzumab Vedotin | 18.7 mL/day/kg | Standard Deviation 5.3 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Clearance (CL) of Polatuzumab Vedotin | 18.9 mL/day/kg | Standard Deviation 5.27 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Clearance (CL) of Polatuzumab Vedotin | 17.7 mL/day/kg | Standard Deviation 3.83 |
Secondary
Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
Secondary
Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | 4.11 Months |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
Secondary
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | 35.45 Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
Secondary
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | 6.87 Months |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | 6.70 Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
Secondary
Maximum Concentration (Cmax) of Polatuzumab Vedotin
Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 373 ng/mL | Standard Deviation 147 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 537 ng/mL | Standard Deviation 184 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 781 ng/mL | Standard Deviation 72.6 |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 1400 ng/mL | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 537 ng/mL | Standard Deviation 59.1 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 557 ng/mL | Standard Deviation 114 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 532 ng/mL | Standard Deviation 163 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Maximum Concentration (Cmax) of Polatuzumab Vedotin | 530 ng/mL | Standard Deviation 138 |
Secondary
Number of Participants With Anti-Obinutuzumab Antibodies
The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA.
Time frame: Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Anti-Obinutuzumab Antibodies | 0 Participants |
Secondary
Number of Participants With Anti-Polatuzumab Vedotin Antibodies
The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 μg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 μg/mL. Polatuzumab vedotin total antibody concentrations ranged from \<0.050 μg/mL to 52.1 μg/mL with a median concentration of 3.38 μg/mL.
Time frame: Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Number of Participants With Anti-Polatuzumab Vedotin Antibodies | 0 Participants |
Secondary
Overall Survival for DLBCL Population
The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.
Time frame: Screening up to death due to any cause (up to approximately 6 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Overall Survival for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Overall Survival for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Overall Survival for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Overall Survival for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Overall Survival for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Overall Survival for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Overall Survival for DLBCL Population | NA Months |
Secondary
Overall Survival for Non-DLBCL Population
The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.
Time frame: Screening up to death due to any cause (up to approximately 6 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Overall Survival for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Overall Survival for Non-DLBCL Population | 15.24 Months |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Overall Survival for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Overall Survival for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Overall Survival for Non-DLBCL Population | NA Months |
Secondary
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.
Time frame: At the end of treatment (Month 6)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 50.0 Percentage of Participants |
| Polatuzumab Vedotin (1.0mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 50.0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 75.0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 75.0 Percentage of Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 15.0 Percentage of Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Complete Response (CR) | 76.5 Percentage of Participants |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population | Partial Response (PR) | 11.8 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.
Time frame: At the end of treatment (Month 6)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.0mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Complete Response (CR) | 100.0 Percentage of Participants |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | Partial Response (PR) | 0 Percentage of Participants |
Secondary
Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score
The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).
Time frame: Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.
Population: The safety population was defined as all participants who have received at least one dose of study medication. TINAS was only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 1 | 0 Score of a Questionnaire | Standard Deviation 0 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 11 | 0.86 Score of a Questionnaire | Standard Deviation 1.21 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 6 | 0.40 Score of a Questionnaire | Standard Deviation 0.55 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 12 | 1.14 Score of a Questionnaire | Standard Deviation 1.21 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 3 | 0.33 Score of a Questionnaire | Standard Deviation 0.58 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 13 | 0.86 Score of a Questionnaire | Standard Deviation 1.21 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 7 | 0.29 Score of a Questionnaire | Standard Deviation 0.49 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 14 | 1.12 Score of a Questionnaire | Standard Deviation 1.73 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Baseline | 0 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 15 | 1.12 Score of a Questionnaire | Standard Deviation 1.73 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 8 | 0.33 Score of a Questionnaire | Standard Deviation 0.52 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 16 | 1.56 Score of a Questionnaire | Standard Deviation 2.07 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 4 | 0.40 Score of a Questionnaire | Standard Deviation 0.55 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 17 | 0.40 Score of a Questionnaire | Standard Deviation 0.55 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 9 | 0.40 Score of a Questionnaire | Standard Deviation 0.55 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 2 | 0.25 Score of a Questionnaire | Standard Deviation 0.5 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 10 | 0.86 Score of a Questionnaire | Standard Deviation 1.21 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 5 | 0.40 Score of a Questionnaire | Standard Deviation 0.55 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 17 | 1.14 Score of a Questionnaire | Standard Deviation 1.46 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 18 | 2 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 19 | 2 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 22 | 1 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Baseline | 0 Score of a Questionnaire | Standard Deviation 0 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 1 | 1 Score of a Questionnaire | Standard Deviation 1.73 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 2 | 0 Score of a Questionnaire | Standard Deviation 0 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 3 | 0.40 Score of a Questionnaire | Standard Deviation 0.89 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 4 | 0.50 Score of a Questionnaire | Standard Deviation 1.22 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 5 | 0.17 Score of a Questionnaire | Standard Deviation 0.41 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 6 | 0.40 Score of a Questionnaire | Standard Deviation 0.89 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 7 | 0.60 Score of a Questionnaire | Standard Deviation 1.34 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 8 | 0.25 Score of a Questionnaire | Standard Deviation 0.71 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 9 | 0.50 Score of a Questionnaire | Standard Deviation 1.07 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 10 | 1.14 Score of a Questionnaire | Standard Deviation 1.46 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 11 | 0.57 Score of a Questionnaire | Standard Deviation 1.13 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 12 | 0.71 Score of a Questionnaire | Standard Deviation 1.25 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 13 | 1.12 Score of a Questionnaire | Standard Deviation 1.81 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 14 | 0.88 Score of a Questionnaire | Standard Deviation 1.36 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 15 | 0.75 Score of a Questionnaire | Standard Deviation 1.16 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score | Week 16 | 1.50 Score of a Questionnaire | Standard Deviation 1.69 |
Secondary
Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score
The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).
Time frame: Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.
Population: The safety population was defined as all participants who have received at least one dose of study medication. TINAS was only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 3 | 0.06 Score of a Questionnaire | Standard Deviation 0.1 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 11 | 0.26 Score of a Questionnaire | Standard Deviation 0.35 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 6 | 0.16 Score of a Questionnaire | Standard Deviation 0.32 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 12 | 0.30 Score of a Questionnaire | Standard Deviation 0.43 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 2 | 0.02 Score of a Questionnaire | Standard Deviation 0.04 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 13 | 0.25 Score of a Questionnaire | Standard Deviation 0.32 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 7 | 0.14 Score of a Questionnaire | Standard Deviation 0.28 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 14 | 0.49 Score of a Questionnaire | Standard Deviation 0.86 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 4 | 0.18 Score of a Questionnaire | Standard Deviation 0.36 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 15 | 0.48 Score of a Questionnaire | Standard Deviation 0.86 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 8 | 0.17 Score of a Questionnaire | Standard Deviation 0.37 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 16 | 0.66 Score of a Questionnaire | Standard Deviation 0.94 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 1 | 0 Score of a Questionnaire | Standard Deviation 0 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 17 | 0.25 Score of a Questionnaire | Standard Deviation 0.52 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 9 | 0.25 Score of a Questionnaire | Standard Deviation 0.47 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 5 | 0.16 Score of a Questionnaire | Standard Deviation 0.32 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 10 | 0.30 Score of a Questionnaire | Standard Deviation 0.41 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Baseline | 0 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 17 | 0.91 Score of a Questionnaire | Standard Deviation 1.44 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 18 | 0.64 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 19 | 0.45 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 22 | 0.09 Score of a Questionnaire | — |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Baseline | 0.32 Score of a Questionnaire | Standard Deviation 0.45 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 1 | 0.91 Score of a Questionnaire | Standard Deviation 0.92 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 2 | 0.07 Score of a Questionnaire | Standard Deviation 0.16 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 3 | 0.22 Score of a Questionnaire | Standard Deviation 0.44 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 4 | 0.26 Score of a Questionnaire | Standard Deviation 0.63 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 5 | 0.17 Score of a Questionnaire | Standard Deviation 0.41 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 6 | 0.25 Score of a Questionnaire | Standard Deviation 0.57 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 7 | 0.35 Score of a Questionnaire | Standard Deviation 0.77 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 8 | 0.31 Score of a Questionnaire | Standard Deviation 0.59 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 9 | 0.38 Score of a Questionnaire | Standard Deviation 0.61 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 10 | 0.53 Score of a Questionnaire | Standard Deviation 0.71 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 11 | 0.39 Score of a Questionnaire | Standard Deviation 0.73 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 12 | 0.65 Score of a Questionnaire | Standard Deviation 1.02 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 13 | 0.78 Score of a Questionnaire | Standard Deviation 1.34 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 14 | 0.62 Score of a Questionnaire | Standard Deviation 1.05 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 15 | 0.70 Score of a Questionnaire | Standard Deviation 1.28 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score | Week 16 | 1.12 Score of a Questionnaire | Standard Deviation 1.61 |
Secondary
Plasma Levels of Cyclophosphamide
Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.
Time frame: End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of cyclophosphamide were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C1D1 0.5hr POSTDOSE | 37.5 ug/mL | Standard Deviation 24.4 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C1D1 3.5hr POSTDOSE | 23.2 ug/mL | Standard Deviation 2.38 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C1D1 23.5hr POSTDOSE | 2.98 ug/mL | Standard Deviation 1.39 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C3D1 0.5hr POSTDOSE | 34.8 ug/mL | Standard Deviation 6.14 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C3D1 3.5hr POSTDOSE | 24.2 ug/mL | Standard Deviation 3.87 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Cyclophosphamide | C3D1 23.5hr POSTDOSE | 3.17 ug/mL | Standard Deviation 1.66 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C3D1 3.5hr POSTDOSE | 22.5 ug/mL | Standard Deviation 4.26 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C1D1 0.5hr POSTDOSE | 32.3 ug/mL | Standard Deviation 7.64 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C3D1 0.5hr POSTDOSE | 35.2 ug/mL | Standard Deviation 13.4 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C1D1 3.5hr POSTDOSE | 22.5 ug/mL | Standard Deviation 3.69 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C3D1 23.5hr POSTDOSE | 3.16 ug/mL | Standard Deviation 1.68 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Cyclophosphamide | C1D1 23.5hr POSTDOSE | 3.32 ug/mL | Standard Deviation 1.5 |
Secondary
Plasma Levels of Doxorubicin
Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.
Time frame: 2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of doxorubicin were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Doxorubicin | C1D1 2hr POSTDOSE | 35.4 ug/mL | Standard Deviation 13.6 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Doxorubicin | C1D1 24hr POSTDOSE | 9.13 ug/mL | Standard Deviation 2.51 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Doxorubicin | C3D1 2hr POSTDOSE | 29.3 ug/mL | Standard Deviation 10.9 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Plasma Levels of Doxorubicin | C3D1 24hr POSTDOSE | 8.68 ug/mL | Standard Deviation 2.05 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Doxorubicin | C3D1 24hr POSTDOSE | 9.14 ug/mL | Standard Deviation 2.12 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Doxorubicin | C1D1 2hr POSTDOSE | 30.2 ug/mL | Standard Deviation 6.82 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Doxorubicin | C3D1 2hr POSTDOSE | 29.6 ug/mL | Standard Deviation 10.8 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Plasma Levels of Doxorubicin | C1D1 24hr POSTDOSE | 11.7 ug/mL | Standard Deviation 11.6 |
Secondary
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population | NA Months |
Secondary
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.
Time frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | 6.87 Months |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population | NA Months |
Secondary
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population
Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.
Time frame: 6 months
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 100.70 Percentage | Standard Deviation 0.99 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 99.97 Percentage | Standard Deviation 0.55 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 96.04 Percentage | Standard Deviation 4.81 |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 99.35 Percentage | Standard Deviation 3.19 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 99.95 Percentage | Standard Deviation 0.75 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 96.71 Percentage | Standard Deviation 6.99 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population | 98.92 Percentage | Standard Deviation 3.74 |
Secondary
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population
Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.
Time frame: 6 months
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 100.00 Percentage | — |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 100.94 Percentage | — |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 132.22 Percentage | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 99.72 Percentage | Standard Deviation 0.06 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population | 100.17 Percentage | Standard Deviation 0.14 |
Secondary
Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin
Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 58.2 mL/kg | Standard Deviation 9.92 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 80.0 mL/kg | Standard Deviation 9.97 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 57.7 mL/kg | Standard Deviation 7.95 |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 41.9 mL/kg | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 67.9 mL/kg | Standard Deviation 7.42 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 87.5 mL/kg | Standard Deviation 19.3 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 96.5 mL/kg | Standard Deviation 34.1 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin | 99.3 mL/kg | Standard Deviation 27.4 |
Secondary
Terminal Half-Life (t1/2) of Polatuzumab Vedotin
t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)
Population: The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polatuzumab Vedotin (1.0mg) + R-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 5.03 days | Standard Deviation 0.905 |
| Polatuzumab Vedotin (1.4mg) + R-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 4.85 days | Standard Deviation 0.72 |
| Polatuzumab Vedotin (1.8mg) + R-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 4.79 days | Standard Deviation 0.675 |
| Polatuzumab Vedotin (2.4mg) + R-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 4.42 days | — |
| Polatuzumab Vedotin (1.4mg) + G-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 5.19 days | Standard Deviation 0.43 |
| Polatuzumab Vedotin (1.8mg) + G-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 4.89 days | Standard Deviation 0.526 |
| Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 5.03 days | Standard Deviation 0.621 |
| Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP | Terminal Half-Life (t1/2) of Polatuzumab Vedotin | 5.50 days | Standard Deviation 0.795 |