Advanced Solid Tumors, Aggressive B-cell Lymphomas
Conditions
Keywords
Advanced Solid tumors, Diffuse Large B-cell Lymphoma, programmed death 1, programmed dealth ligand 1, cytotoxic T-lymphocyte-associated antigen-4, OX40 ligand
Brief summary
The main purpose of this study is to determine the best dose of MEDI6469 that is safe and tolerable when given as monotherapy and in combination with tremelimumab, MEDI4736 (durvalumab), or rituximab in participants with either advanced solid tumors or diffuse large B-cell lymphoma (DLBCL). Tremelimumab and MEDI4736 (durvalumab) will be tested with MEDI6469 in a set of participants with advanced solid tumors while rituximab will be tested with MEDI6469 in participants with DLBCL. MEDI6469 will be tested as monotherapy in participants with advanced solid tumors.
Interventions
BIOLOGICALMEDI6469 Monotherapy
single intravenous (IV) administration of MEDI6469
BIOLOGICALMEDI6469 Plus Tremelimumab
MEDI6469 in combination with Tremelimumab
BIOLOGICALMEDI6469 Plus Durvalumab
MEDI6469 in combination with Durvalumab
BIOLOGICALMEDI6469 plus Rituximab
MEDI6469 in combination with Rituximab
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Adults \>/= 18 years old * Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B) * At least one lesion measurable by RECIST not previously irradiated (Monotherapy and in Cohorts A and B) * Histologically confirmed DLBCL(Cohort C) * Adequate organ and marrow function * ECOG performance status of 0 or 1 * Willingness to provide consent for biopsy samples
Exclusion criteria
* Prior exposure to immunotherapy (either as a single agent or in combination) including but not limited to CD137 or OX40 agonists, anti-CTLA-4, anti-PD-1, or anti-PD-L1, anti-PD-L2 antibody or pathway-targeting agents * History of organ transplant that requires use of immunosuppressives * History of primary immunodeficiency or tuberculosis * Active or prior documented autoimmune disease within the past 3 years * Active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months * Major surgical procedure within 30 days prior to the first dose of investigational product or still recovering from prior surgery * Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of MEDI6469 | From the first dose of study treatment through 28 days after the first dose (up to 28 days) | The MTD was the highest dose within a cohort where no more than 1 out of 6 participants experienced dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD. |
| Number of Participants With DLTs | From the first dose of study treatment through 28 days after the first dose (up to 28 days) | The DLT was any Grade 3 or higher treatment-related toxicity (including liver transaminase elevation higher than 8×upper limit of normal \[ULN\] or total bilirubin higher than 5×ULN; any \>=Grade 2 pneumonitis that did not resolve to \<=Grade 1 within 3 days) that occurred during the DLT time frame, and excluded the following: Grade 3 fatigue for less than or equal to (\<=) 7 days; Grade 3 endocrinopathy that was managed and the participant was asymptomatic; Grade 3 inflammatory reaction attributed to a local antitumor response that resolved to \<=Grade 1 within 30 days; concurrent vitiligo or alopecia of any grade; Grade 3 infusion-related reaction that resolved within 6 hours; and any more than or equal to (\>=) Grade 3 lymphopenia (unless clinically significant). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year) | An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs were events present at baseline that worsened in intensity after administration of study treatment or events absent at baseline that emerged after administration of study treatment. |
| Number of Participants With Treatment-emergent Serious Adverse Events | From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year) | A serious adverse event (SAE) was any AE that resulted in death, immediately life threatening, required (or prolonged) inpatient (or existing) hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect in offspring of the participant, or an important medical event that could jeopardize the participant or required medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs present at baseline that worsened in intensity after administration of study treatment or SAEs absent at baseline that emerged after administration of study treatment. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year) | Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell \[WBC\] count with differential, red blood cell \[RBC\] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume \[MCV\], and mean corpuscular hemoglobin concentration \[MCHC\]); serum chemistry (calcium, chloride, magnesium, creatinine, sodium, blood urea nitrogen \[BUN\], bicarbonate, glucose, aspartate transaminase \[AST\], total bilirubin, C-reactive protein, gamma-glutamyl transpeptidase \[GGT\], lactate dehydrogenase, uric acid, potassium, alanine transaminase \[ALT\], alkaline phosphatase, albumin, total protein, triglycerides, and cholesterol); urinalysis; and coagulation parameters. |
| Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year) | Vital signs examination included assessment of temperature, blood pressure, pulse rate, and respiratory rate. Physical examination included assessments of head, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems. The TEAEs related to these vital sign and physical examination abnormalities were reported. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year) | Electrocardiogram (ECG) parameters included atrial rate, PR interval, QRS duration, QTC interval, QT interval, and ventricular rate. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to these ECG evaluation abnormalities were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) | MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment | The pharmacokinetics (PK) parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469 |
| Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment. | The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469 |
| Best Overall Response (BOR) | From study entry until early termination (up to 1 year) | Best overall response: Percentage (%) of participants with CR, partial response (PR), stable disease (SD), progressive disease (PD), or non-evaluable disease based on revised Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Per RECIST v1.1: CR-disappearance of all target/non-target lesions; PR at least a 30% decrease in sum of diameters of target lesions; SD-neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD-at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Per Cheson criteria: CR-disappearance of all evidence of disease; PR-regression of measurable disease and no new sites; SD-failure to attain CR/PR or PD; PD-any new lesion or increase by at least 50% of previously involved sites from nadir. |
| Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | All treatment arms: Days 8, 15, 29, and end of treatment (up to 1 year). Additionally for MEDI6469 + rituximab arm: Days 3, 31, 59, and every 28 days thereafter until end of treatment (up to 1 year) | The number of participants who developed detectable HAMA are presented. ImmuSTRIP® HAMA IgG ELISA Test System was used for detection, confirmation, and titration of HAMA in human serum with a HAMA positivity cut-off level of 74 nanogram per millilitre (ng/mL). |
| Terminal Phase Elimination Half-Life (T1/2) | MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment. | The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469 |
| Objective Response Rate (ORR) | From study entry until early termination (up to 1 year) | Objective response rate was defined as the percentage of participants with confirmed CR or confirmed PR according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Confirmed CR and PR were those that persisted on repeat consecutive assessment \>= 4 weeks after the initial documentation of response. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR - disappearance of all target/non-target lesions; PR - at least a 30% decrease in the sum of the diameters of target lesions. Tumor assessments according to Cheson criteria were defined as follows: CR - disappearance of all evidence of disease; PR- regression of measurable disease and no new sites. |
| Disease Control Rate | From study entry until early termination (up to 1 year) | Disease control rate: Percentage of participants with CR, PR, or SD (if they maintained SD for \>= 8 weeks) according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR -disappearance of all target/non-target lesions; PR - at least a 30% decrease in sum of diameters of target lesions; SD - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD - at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Tumor assessments according to Cheson criteria were defined as follows: CR- disappearance of all evidence of disease; PR - regression of measurable disease and no new sites; SD- failure to attain CR/PR or PD; PD- any new lesion or increase by at least 50% of previously involved sites from nadir. |
| Duration of Response (DOR) | From Study entry until early termination (up to 1 year) | Duration of response was the duration from the first documented objective response to the first documented PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir. |
| Systemic Clearance (CL) | MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment. | The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469 |
| Progression-free Survival (PFS) | From Study entry until early termination (up to 1 year) | Progression-free survival was the duration measured from the start of study treatment until the first documentation of PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir. |
| Overall Survival (OS) | From Study entry until early termination (up to 1 year) | The OS was the duration from the start of study treatment until death due to any cause. |
Countries
United States
Participant flow
Recruitment details
A total of 58 participants were screened at 13 sites in the United States of America (USA).
Pre-assignment details
A total of 58 participants were screened for this study, of which 48 participants were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| MEDI6469 6 Milligram/Kilogram (mg/kg) Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 | 8 |
| MEDI6469 10 mg/kg Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 | 6 |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus tremelimumab 3 mg/kg as IV administration on Day 1, then every 4 weeks (Q4W) for 6 doses, after which every 12 weeks (Q12W) for 2 doses or until PD | 3 |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus tremelimumab 10 mg/kg as IV administration on Day 1, then Q4W for 6 doses, after which Q12W for 2 doses or until PD | 7 |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus durvalumab 3 mg/kg as IV administration on Day 1, then every 2 weeks (Q2W) for 12 months or until PD | 6 |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus durvalumab 10 mg/kg as IV administration on Day 1, then Q2W for 12 months or until PD | 7 |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 plus durvalumab 10 mg/kg as IV administration on Day 1, then Q2W for 12 months or until PD | 7 |
| MEDI6469 2 mg/kg+Rituximab 375 mg/m^2 Participants received MEDI6469 2 mg/kg as a repeat IV administration on Day 3 then Q4W for 11 doses, or until confirmed complete response (CR) plus 1 cycle or PD plus rituximab 375 mg/m\^2 as IV administration on Days 1, 8, and 29; then Q4W for 10 doses, or until confirmed CR plus 1 cycle, or PD | 3 |
| MEDI6469 10 mg/kg+Rituximab 375 mg/m^2 Participants received MEDI6469 10 mg/kg as a repeat IV administration on Day 3, then Q4W for 11 doses, or until confirmed CR plus 1 cycle, or PD plus rituximab 375 mg/m\^2 as IV administration on Days 1, 8, and 29; then Q4W for 10 doses, or until confirmed CR plus 1 cycle, or PD | 1 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 5 | 6 | 2 | 6 | 5 | 3 | 3 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | MEDI6469 6 Milligram/Kilogram (mg/kg) | MEDI6469 10 mg/kg | MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | MEDI6469 2 mg/kg+Rituximab 375 mg/m^2 | MEDI6469 10 mg/kg+Rituximab 375 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 12.6 | 63.8 Years STANDARD_DEVIATION 8.9 | 48.0 Years STANDARD_DEVIATION 6.9 | 61.3 Years STANDARD_DEVIATION 8.7 | 57.5 Years STANDARD_DEVIATION 19.4 | 66.6 Years STANDARD_DEVIATION 14.5 | 62.6 Years STANDARD_DEVIATION 9.1 | 70.3 Years STANDARD_DEVIATION 4.6 | 73.0 Years | 61.9 Years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 28 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 6 / 6 | 3 / 3 | 7 / 7 | 6 / 6 | 7 / 7 | 7 / 7 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 4 / 8 | 3 / 6 | 1 / 3 | 5 / 7 | 3 / 6 | 3 / 7 | 3 / 7 | 2 / 3 | 0 / 1 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of MEDI6469
The MTD was the highest dose within a cohort where no more than 1 out of 6 participants experienced dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD.
Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
Population: DLT-evaluable population: All participants enrolled in the dose-escalation phase who received study treatment per protocol during the first 28 days and completed safety follow-up through the DLT-evaluation period or experienced any DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 10 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Maximum Tolerated Dose (MTD) of MEDI6469 | NA milligram per kilogram (mg/kg) |
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell \[WBC\] count with differential, red blood cell \[RBC\] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume \[MCV\], and mean corpuscular hemoglobin concentration \[MCHC\]); serum chemistry (calcium, chloride, magnesium, creatinine, sodium, blood urea nitrogen \[BUN\], bicarbonate, glucose, aspartate transaminase \[AST\], total bilirubin, C-reactive protein, gamma-glutamyl transpeptidase \[GGT\], lactate dehydrogenase, uric acid, potassium, alanine transaminase \[ALT\], alkaline phosphatase, albumin, total protein, triglycerides, and cholesterol); urinalysis; and coagulation parameters.
Time frame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Population: As-treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 2 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 2 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 1 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 3 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 3 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 3 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 2 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thyroxine free decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperuricemia | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypernatremia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperglycemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Troponin increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hemoglobin decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood thyroid stimulating hormone increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphatemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood iron decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood cholesterol increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Tri-iodothyronine free decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypothyroidism | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutrophil count decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood glucose increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Liver function test increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Platelet count decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphocyte count decreased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypokalemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercalcemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Iron deficiency | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperkalemia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminemia | 0 Participant |
Primary
Number of Participants With DLTs
The DLT was any Grade 3 or higher treatment-related toxicity (including liver transaminase elevation higher than 8×upper limit of normal \[ULN\] or total bilirubin higher than 5×ULN; any \>=Grade 2 pneumonitis that did not resolve to \<=Grade 1 within 3 days) that occurred during the DLT time frame, and excluded the following: Grade 3 fatigue for less than or equal to (\<=) 7 days; Grade 3 endocrinopathy that was managed and the participant was asymptomatic; Grade 3 inflammatory reaction attributed to a local antitumor response that resolved to \<=Grade 1 within 30 days; concurrent vitiligo or alopecia of any grade; Grade 3 infusion-related reaction that resolved within 6 hours; and any more than or equal to (\>=) Grade 3 lymphopenia (unless clinically significant).
Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
Population: DLT-evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With DLTs | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With DLTs | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With DLTs | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With DLTs | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With DLTs | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With DLTs | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With DLTs | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With DLTs | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With DLTs | 0 Participant |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Electrocardiogram (ECG) parameters included atrial rate, PR interval, QRS duration, QTC interval, QT interval, and ventricular rate. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to these ECG evaluation abnormalities were reported.
Time frame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participant |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs were events present at baseline that worsened in intensity after administration of study treatment or events absent at baseline that emerged after administration of study treatment.
Time frame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Population: As-treated population: all the participants who received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 8 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participant |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events
A serious adverse event (SAE) was any AE that resulted in death, immediately life threatening, required (or prolonged) inpatient (or existing) hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect in offspring of the participant, or an important medical event that could jeopardize the participant or required medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs present at baseline that worsened in intensity after administration of study treatment or SAEs absent at baseline that emerged after administration of study treatment.
Time frame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 4 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 3 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 5 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 3 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 3 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Treatment-emergent Serious Adverse Events | 3 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Treatment-emergent Serious Adverse Events | 2 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Treatment-emergent Serious Adverse Events | 0 Participant |
Primary
Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs
Vital signs examination included assessment of temperature, blood pressure, pulse rate, and respiratory rate. Physical examination included assessments of head, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems. The TEAEs related to these vital sign and physical examination abnormalities were reported.
Time frame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Population: As-treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 1 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 0 Participant |
| MEDI6469 6 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 2 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 1 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 2 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 3 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 2 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 1 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 1 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 2 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 1 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypotension | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypertension | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Sinus tachycardia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Tachycardia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea exertional | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Hypoxia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Dyspnea | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Wheezing | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Pyrexia | 0 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs | Bradycardia | 0 Participant |
Secondary
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Time frame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
Population: All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI6469 6 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 556.92 day*microgram per milliliter | Standard Deviation 166.95 |
| MEDI6469 10 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 873.16 day*microgram per milliliter | Standard Deviation 328.74 |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 169.34 day*microgram per milliliter | Standard Deviation 18.15 |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 183.09 day*microgram per milliliter | Standard Deviation 26.27 |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 144.91 day*microgram per milliliter | Standard Deviation 33.07 |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 169.65 day*microgram per milliliter | Standard Deviation 45.98 |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 998.25 day*microgram per milliliter | Standard Deviation 400.12 |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 145.55 day*microgram per milliliter | Standard Deviation 16.86 |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 1619.73 day*microgram per milliliter | — |
Secondary
Best Overall Response (BOR)
Best overall response: Percentage (%) of participants with CR, partial response (PR), stable disease (SD), progressive disease (PD), or non-evaluable disease based on revised Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Per RECIST v1.1: CR-disappearance of all target/non-target lesions; PR at least a 30% decrease in sum of diameters of target lesions; SD-neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD-at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Per Cheson criteria: CR-disappearance of all evidence of disease; PR-regression of measurable disease and no new sites; SD-failure to attain CR/PR or PD; PD-any new lesion or increase by at least 50% of previously involved sites from nadir.
Time frame: From study entry until early termination (up to 1 year)
Population: As-treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI6469 6 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 6 mg/kg | Best Overall Response (BOR) | NE | 37.5 Percentage of participants |
| MEDI6469 6 mg/kg | Best Overall Response (BOR) | SD | 12.5 Percentage of participants |
| MEDI6469 6 mg/kg | Best Overall Response (BOR) | PD | 50.0 Percentage of participants |
| MEDI6469 6 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 10 mg/kg | Best Overall Response (BOR) | NE | 66.7 Percentage of participants |
| MEDI6469 10 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 10 mg/kg | Best Overall Response (BOR) | SD | 0 Percentage of participants |
| MEDI6469 10 mg/kg | Best Overall Response (BOR) | PD | 33.3 Percentage of participants |
| MEDI6469 10 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Best Overall Response (BOR) | SD | 33.3 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Best Overall Response (BOR) | NE | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Best Overall Response (BOR) | PD | 66.7 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Best Overall Response (BOR) | PD | 42.9 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Best Overall Response (BOR) | NE | 28.6 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Best Overall Response (BOR) | SD | 28.6 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Best Overall Response (BOR) | PD | 50.0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Best Overall Response (BOR) | SD | 33.3 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Best Overall Response (BOR) | NE | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Best Overall Response (BOR) | PR | 16.7 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | SD | 14.3 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | NE | 42.9 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | PD | 42.9 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | SD | 0 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | PD | 100.0 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Best Overall Response (BOR) | NE | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Best Overall Response (BOR) | SD | 33.3 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Best Overall Response (BOR) | NE | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Best Overall Response (BOR) | PD | 66.7 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Best Overall Response (BOR) | CR | 0 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Best Overall Response (BOR) | SD | 100.0 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Best Overall Response (BOR) | PR | 0 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Best Overall Response (BOR) | PD | 0 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Best Overall Response (BOR) | NE | 0 Percentage of participants |
Secondary
Disease Control Rate
Disease control rate: Percentage of participants with CR, PR, or SD (if they maintained SD for \>= 8 weeks) according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR -disappearance of all target/non-target lesions; PR - at least a 30% decrease in sum of diameters of target lesions; SD - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD - at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Tumor assessments according to Cheson criteria were defined as follows: CR- disappearance of all evidence of disease; PR - regression of measurable disease and no new sites; SD- failure to attain CR/PR or PD; PD- any new lesion or increase by at least 50% of previously involved sites from nadir.
Time frame: From study entry until early termination (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Disease Control Rate | 12.5 Percentage of participants |
| MEDI6469 10 mg/kg | Disease Control Rate | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Disease Control Rate | 33.3 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Disease Control Rate | 28.6 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Disease Control Rate | 50.0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Disease Control Rate | 14.3 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Disease Control Rate | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Disease Control Rate | 33.3 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Disease Control Rate | 100.0 Percentage of participants |
Secondary
Duration of Response (DOR)
Duration of response was the duration from the first documented objective response to the first documented PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir.
Time frame: From Study entry until early termination (up to 1 year)
Population: All the participants with an OR were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Duration of Response (DOR) | 368 Days |
Secondary
Maximum Observed Serum Concentration (Cmax)
The pharmacokinetics (PK) parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Time frame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment
Population: All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI6469 6 mg/kg | Maximum Observed Serum Concentration (Cmax) | 133.76 microgram per milliliter | Standard Deviation 34.87 |
| MEDI6469 10 mg/kg | Maximum Observed Serum Concentration (Cmax) | 188.87 microgram per milliliter | Standard Deviation 59.88 |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Maximum Observed Serum Concentration (Cmax) | 49.00 microgram per milliliter | Standard Deviation 1.29 |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Maximum Observed Serum Concentration (Cmax) | 43.67 microgram per milliliter | Standard Deviation 7.99 |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Maximum Observed Serum Concentration (Cmax) | 40.21 microgram per milliliter | Standard Deviation 8.2 |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Maximum Observed Serum Concentration (Cmax) | 42.10 microgram per milliliter | Standard Deviation 6.63 |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Maximum Observed Serum Concentration (Cmax) | 234.91 microgram per milliliter | Standard Deviation 56.05 |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) | 31.68 microgram per milliliter | Standard Deviation 5.06 |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) | 289.40 microgram per milliliter | — |
Secondary
Number of Participants Positive for Human Anti-mouse Antibodies (HAMA)
The number of participants who developed detectable HAMA are presented. ImmuSTRIP® HAMA IgG ELISA Test System was used for detection, confirmation, and titration of HAMA in human serum with a HAMA positivity cut-off level of 74 nanogram per millilitre (ng/mL).
Time frame: All treatment arms: Days 8, 15, 29, and end of treatment (up to 1 year). Additionally for MEDI6469 + rituximab arm: Days 3, 31, 59, and every 28 days thereafter until end of treatment (up to 1 year)
Population: All the participants who received at least a one dose of MEDI6469.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 5 Participant |
| MEDI6469 10 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 4 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 3 Participant |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 6 Participant |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 5 Participant |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 6 Participant |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 4 Participant |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 1 Participant |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Number of Participants Positive for Human Anti-mouse Antibodies (HAMA) | 0 Participant |
Secondary
Objective Response Rate (ORR)
Objective response rate was defined as the percentage of participants with confirmed CR or confirmed PR according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Confirmed CR and PR were those that persisted on repeat consecutive assessment \>= 4 weeks after the initial documentation of response. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR - disappearance of all target/non-target lesions; PR - at least a 30% decrease in the sum of the diameters of target lesions. Tumor assessments according to Cheson criteria were defined as follows: CR - disappearance of all evidence of disease; PR- regression of measurable disease and no new sites.
Time frame: From study entry until early termination (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI6469 6 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 10 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Objective Response Rate (ORR) | 16.7 Percentage of participants |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Objective Response Rate (ORR) | 0 Percentage of participants |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Overall Survival (OS)
The OS was the duration from the start of study treatment until death due to any cause.
Time frame: From Study entry until early termination (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI6469 6 mg/kg | Overall Survival (OS) | 6.1 Months |
| MEDI6469 10 mg/kg | Overall Survival (OS) | 6.5 Months |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Overall Survival (OS) | 13.1 Months |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Overall Survival (OS) | 6.7 Months |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Overall Survival (OS) | 11.2 Months |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Overall Survival (OS) | NA Months |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Overall Survival (OS) | 2.9 Months |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Overall Survival (OS) | 3.3 Months |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Overall Survival (OS) | NA Months |
Secondary
Progression-free Survival (PFS)
Progression-free survival was the duration measured from the start of study treatment until the first documentation of PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir.
Time frame: From Study entry until early termination (up to 1 year)
Population: As-treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI6469 6 mg/kg | Progression-free Survival (PFS) | 1.8 Months |
| MEDI6469 10 mg/kg | Progression-free Survival (PFS) | 1.8 Months |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Progression-free Survival (PFS) | 1.9 Months |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Progression-free Survival (PFS) | 2.8 Months |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Progression-free Survival (PFS) | 5.6 Months |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Progression-free Survival (PFS) | 1.8 Months |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Progression-free Survival (PFS) | 1.4 Months |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Progression-free Survival (PFS) | 1.0 Months |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Progression-free Survival (PFS) | 5.4 Months |
Secondary
Systemic Clearance (CL)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Time frame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
Population: All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI6469 6 mg/kg | Systemic Clearance (CL) | 0.81 liter per day | Standard Deviation 0.224 |
| MEDI6469 10 mg/kg | Systemic Clearance (CL) | 0.84 liter per day | Standard Deviation 0.246 |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Systemic Clearance (CL) | 1.02 liter per day | Standard Deviation 0.155 |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Systemic Clearance (CL) | 0.89 liter per day | Standard Deviation 0.132 |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Systemic Clearance (CL) | 1.04 liter per day | Standard Deviation 0.288 |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Systemic Clearance (CL) | 1.0 liter per day | Standard Deviation 0.266 |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Systemic Clearance (CL) | 0.84 liter per day | Standard Deviation 0.173 |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Systemic Clearance (CL) | 1.11 liter per day | Standard Deviation 0.188 |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Systemic Clearance (CL) | 0.77 liter per day | — |
Secondary
Terminal Phase Elimination Half-Life (T1/2)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Time frame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
Population: All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI6469 6 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 2.83 Day | Standard Deviation 0.83 |
| MEDI6469 10 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 3.20 Day | Standard Deviation 1.23 |
| MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 1.56 Day | Standard Deviation 0.04 |
| MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 2.86 Day | Standard Deviation 0.68 |
| MEDI6469 2 mg/kg+Durvalumab 3 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 2.73 Day | Standard Deviation 0.65 |
| MEDI6469 2 mg/kg+Durvalumab 10 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 3.30 Day | Standard Deviation 0.68 |
| MEDI6469 10 mg/kg+Durvalumab 10 mg/kg | Terminal Phase Elimination Half-Life (T1/2) | 2.98 Day | Standard Deviation 1.06 |
| MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 | Terminal Phase Elimination Half-Life (T1/2) | 3.75 Day | Standard Deviation 1.03 |
| MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 | Terminal Phase Elimination Half-Life (T1/2) | 4.19 Day | — |