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A Phase 1b/2 Safety and Tolerability Study of MEDI6469 in Combination With Therapeutic Immune Agents or Monoclonal Antibodies

Sponsor
MedImmune LLC (Industry)
Overall Status
Terminated
CT.gov ID
NCT02205333
Collaborator
(none)
48
Enrollment
13
Locations
9
Arms
19.8
Actual Duration (Months)
3.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: MEDI6469 Monotherapy
  • Biological: MEDI6469 Plus Tremelimumab
  • Biological: MEDI6469 Plus Durvalumab
  • Biological: MEDI6469 plus Rituximab
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
48 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Open-label Study to Evaluate the Safety and Tolerability of MEDI6469 in Combination With Immune Therapeutic Agents or Therapeutic Monoclonal Antibodies in Subjects With Selected Advanced Solid Tumors or Aggressive B-cell Lymphomas
Actual Study Start Date :
Aug 13, 2014
Actual Primary Completion Date :
Apr 8, 2016
Actual Study Completion Date :
Apr 8, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: MEDI6469 6 mg/kg

Participants received MEDI6469 6 milligram/kilogram (mg/kg) as a single intravenous (IV) administration on Day 1

Biological: MEDI6469 Monotherapy
single intravenous (IV) administration of MEDI6469
Experimental: MEDI6469 10 mg/kg

Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1

Biological: MEDI6469 Monotherapy
single intravenous (IV) administration of MEDI6469
Experimental: MEDI6469 2 mg/kg+Tremelimumab 3 mg/k

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

Biological: MEDI6469 Plus Tremelimumab
MEDI6469 in combination with Tremelimumab
Experimental: 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 progression of disease (PD)

Biological: MEDI6469 Plus Tremelimumab
MEDI6469 in combination with Tremelimumab
Experimental: 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

Biological: MEDI6469 Plus Durvalumab
MEDI6469 in combination with Durvalumab
Experimental: 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

Biological: MEDI6469 Plus Durvalumab
MEDI6469 in combination with Durvalumab
Experimental: 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

Biological: MEDI6469 Plus Durvalumab
MEDI6469 in combination with Durvalumab
Experimental: 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

Biological: MEDI6469 plus Rituximab
MEDI6469 in combination with Rituximab
Experimental: 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/m2 as IV administration on Days 1, 8, and 29; then Q4W for 10 doses, or until confirmed CR plus 1 cycle, or PD

Biological: MEDI6469 plus Rituximab
MEDI6469 in combination with Rituximab

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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 Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Scottsdale Arizona United States 85259
2 Research Site Sacramento California United States 95817
3 Research Site Santa Monica California United States 90404
4 Research Site Washington, D.C. District of Columbia United States 20007
5 Research Site Tampa Florida United States 33612
6 Research Site Chicago Illinois United States 60611
7 Research Site Detroit Michigan United States 48202
8 Research Site Las Vegas Nevada United States 89169
9 Research Site Hackensack New Jersey United States 7601
10 Research Site Huntersville North Carolina United States 28078
11 Research Site Portland Oregon United States 97213
12 Research Site Memphis Tennessee United States 38120
13 Research Site Houston Texas United States 77030

Sponsors and Collaborators

  • MedImmune LLC

Investigators

  • Study Director: MedImmune, LLC, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02205333
Other Study ID Numbers:
  • D4981C00001
First Posted:
Jul 31, 2014
Last Update Posted:
Jun 28, 2017
Last Verified:
Jun 1, 2017
Keywords provided by MedImmune LLC
Advanced Solid tumors
Diffuse Large B-cell Lymphoma
programmed death 1
programmed dealth ligand 1
cytotoxic T-lymphocyte-associated antigen-4
OX40 ligand
Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Aggression
Rituximab
Durvalumab
Tremelimumab

Study Results

Participant Flow

Recruitment Details A total of 58 participants were screened at 13 sites in the United States of America (USA).
Pre-assignment Detail A total of 58 participants were screened for this study, of which 48 participants were enrolled and received study treatment.
Arm/Group Title 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Period Title: Overall Study
STARTED 8 6 3 7 6 7 7 3 1
COMPLETED 2 0 1 0 1 4 2 1 1
NOT COMPLETED 6 6 2 7 5 3 5 2 0

Baseline Characteristics

Arm/Group Title 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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 Total of all reporting groups
Overall Participants 8 6 3 7 6 7 7 3 1 48
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
60.5
(12.6)
63.8
(8.9)
48.0
(6.9)
61.3
(8.7)
57.5
(19.4)
66.6
(14.5)
62.6
(9.1)
70.3
(4.6)
73.0
(NA)
61.9
(12.2)
Sex: Female, Male (Count of Participants)
Female
5
62.5%
3
50%
2
66.7%
2
28.6%
3
50%
1
14.3%
3
42.9%
1
33.3%
0
0%
20
41.7%
Male
3
37.5%
3
50%
1
33.3%
5
71.4%
3
50%
6
85.7%
4
57.1%
2
66.7%
1
100%
28
58.3%

Outcome Measures

1. Primary Outcome
Title Maximum Tolerated Dose (MTD) of MEDI6469
Description 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)

Outcome Measure Data

Analysis Population Description
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/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [milligram per kilogram (mg/kg)]
NA
NA
NA
NA
NA
NA
NA
NA
NA
2. Primary Outcome
Title Number of Participants With DLTs
Description 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)

Outcome Measure Data

Analysis Population Description
DLT-evaluable population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Participant]
0
0
0
1
1
1
0
0
0
3. Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population: all the participants who received any study treatment.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Participant]
8
6
3
7
6
7
7
3
1
4. Primary Outcome
Title Number of Participants With Treatment-emergent Serious Adverse Events
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Participant]
4
3
1
5
3
3
3
2
0
5. Primary Outcome
Title Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Anemia
2
2
2
2
2
1
3
1
1
Neutrophil count increased
1
0
0
0
0
0
0
0
0
Neutrophil count decreased
0
0
2
0
0
0
0
0
0
Lymphopenia
1
0
0
0
1
0
0
0
0
Blood iron decreased
0
0
0
0
1
0
0
0
0
Hemoglobin decreased
1
0
0
0
0
0
0
0
0
Lymphocyte count decreased
0
0
0
0
1
0
0
0
0
Neutropenia
0
0
0
0
0
0
0
0
1
Platelet count decreased
0
0
0
0
0
1
0
0
0
Thrombocytopenia
0
0
0
0
0
0
0
0
1
Hypernatremia
1
1
1
3
2
0
2
0
0
Hypokalemia
1
1
1
2
1
1
1
1
0
Aspartate aminotransferase increased
1
0
0
3
1
1
1
0
1
Hypomagnesemia
1
1
0
0
2
1
1
1
0
Blood alkaline phosphatase increased
0
0
1
1
2
1
0
0
0
Hyperglycemia
2
0
1
1
1
0
0
0
0
Alanine aminotransferase increased
1
0
0
1
0
1
1
0
0
Blood creatinine increased
0
0
0
1
2
0
0
0
1
Gamma-glutamyltransferase increased
1
0
0
1
2
0
0
0
0
Hypercalcemia
2
1
0
0
0
0
0
1
0
Hyperkalemia
0
0
2
0
2
0
0
0
0
Hypoalbuminemia
1
0
0
0
2
1
0
0
0
Hyperuricemia
0
0
0
0
1
0
0
1
1
Blood bilirubin increased
0
0
0
1
0
1
0
0
0
Hypophosphatemia
1
0
0
0
0
1
0
0
0
Blood cholesterol increased
0
0
1
0
0
0
0
0
0
Blood glucose increased
0
0
0
0
0
0
0
1
0
Blood thyroid stimulating hormone increased
0
0
0
0
1
0
0
0
0
Hypocalcemia
0
1
0
0
0
0
0
0
0
Hypothyroidism
0
0
0
0
1
0
0
0
0
Iron deficiency
0
1
0
0
0
0
0
0
0
Liver function test increased
0
0
0
1
0
0
0
0
0
Tri-iodothyronine free decreased
0
0
0
0
1
0
0
0
0
Troponin increased
0
0
0
0
0
1
0
0
0
Thyroxine free decreased
0
0
0
0
1
0
0
0
0
Hematuria
0
0
1
0
0
0
0
0
0
Activated partial thromboplastin time prolonged
0
0
0
0
1
0
0
1
0
6. Primary Outcome
Title Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Pyrexia
1
2
2
2
0
3
2
0
0
Dyspnea
0
2
1
0
1
2
1
0
1
Hypotension
0
0
0
1
1
1
1
0
0
Sinus tachycardia
0
0
0
1
0
1
0
1
0
Dyspnea exertional
0
0
0
0
1
1
0
0
0
Tachycardia
0
0
1
0
0
1
0
0
0
Bradycardia
0
0
0
0
0
1
0
0
0
Hypertension
0
0
1
0
0
0
0
0
0
Hypoxia
0
0
0
1
0
0
0
0
0
Wheezing
0
0
0
0
0
1
0
0
0
7. Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Participant]
0
0
0
0
0
0
0
0
0
8. Secondary Outcome
Title Best Overall Response (BOR)
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
CR
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
PR
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
SD
12.5
156.3%
0
0%
33.3
1110%
28.6
408.6%
33.3
555%
14.3
204.3%
0
0%
33.3
1110%
100.0
10000%
PD
50.0
625%
33.3
555%
66.7
2223.3%
42.9
612.9%
50.0
833.3%
42.9
612.9%
100.0
1428.6%
66.7
2223.3%
0
0%
NE
37.5
468.8%
66.7
1111.7%
0
0%
28.6
408.6%
0
0%
42.9
612.9%
0
0%
0
0%
0
0%
9. Secondary Outcome
Title Objective Response Rate (ORR)
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Percentage of participants]
0
0%
0
0%
0
0%
0
0%
16.7
278.3%
0
0%
0
0%
0
0%
0
0%
10. Secondary Outcome
Title Disease Control Rate
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Percentage of participants]
12.5
156.3%
0
0%
33.3
1110%
28.6
408.6%
50.0
833.3%
14.3
204.3%
0
0%
33.3
1110%
100.0
10000%
11. Secondary Outcome
Title Duration of Response (DOR)
Description 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)

Outcome Measure Data

Analysis Population Description
All the participants with an OR were included.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 0 0 0 0 1 0 0 0 0
Number [Days]
368
12. Secondary Outcome
Title Progression-free Survival (PFS)
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Median (95% Confidence Interval) [Months]
1.8
1.8
1.9
2.8
5.6
1.8
1.4
1.0
5.4
13. Secondary Outcome
Title Overall Survival (OS)
Description 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)

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Median (95% Confidence Interval) [Months]
6.1
6.5
13.1
6.7
11.2
NA
2.9
3.3
NA
14. Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax)
Description 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

Outcome Measure Data

Analysis Population Description
All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Mean (Standard Deviation) [microgram per milliliter]
133.76
(34.87)
188.87
(59.88)
49.00
(1.29)
43.67
(7.99)
40.21
(8.20)
42.10
(6.63)
234.91
(56.05)
31.68
(5.06)
289.40
(NA)
15. Secondary Outcome
Title Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Description 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.

Outcome Measure Data

Analysis Population Description
All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Mean (Standard Deviation) [day*microgram per milliliter]
556.92
(166.95)
873.16
(328.74)
169.34
(18.15)
183.09
(26.27)
144.91
(33.07)
169.65
(45.98)
998.25
(400.12)
145.55
(16.86)
1619.73
(NA)
16. Secondary Outcome
Title Systemic Clearance (CL)
Description 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.

Outcome Measure Data

Analysis Population Description
All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Mean (Standard Deviation) [liter per day]
0.81
(0.224)
0.84
(0.246)
1.02
(0.155)
0.89
(0.132)
1.04
(0.288)
1.0
(0.266)
0.84
(0.173)
1.11
(0.188)
0.77
(NA)
17. Secondary Outcome
Title Terminal Phase Elimination Half-Life (T1/2)
Description 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.

Outcome Measure Data

Analysis Population Description
All the participants who received at least a one dose of MEDI6469 and for whom PK blood samples were collected and evaluated.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Mean (Standard Deviation) [Day]
2.83
(0.83)
3.20
(1.23)
1.56
(0.04)
2.86
(0.68)
2.73
(0.65)
3.30
(0.68)
2.98
(1.06)
3.75
(1.03)
4.19
(NA)
18. Secondary Outcome
Title Number of Participants Positive for Human Anti-mouse Antibodies (HAMA)
Description 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)

Outcome Measure Data

Analysis Population Description
All the participants who received at least a one dose of MEDI6469.
Arm/Group Title MEDI6469 6 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
Measure Participants 8 6 3 7 6 7 7 3 1
Number [Participant]
5
4
3
6
5
6
4
1
0

Adverse Events

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)
Adverse Event Reporting Description
Arm/Group Title 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
Arm/Group Description Participants received MEDI6469 6 mg/kg as a single intravenous (IV) administration on Day 1 Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 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 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 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 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 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 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 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
All Cause Mortality
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/8 (50%) 3/6 (50%) 1/3 (33.3%) 5/7 (71.4%) 3/6 (50%) 3/7 (42.9%) 3/7 (42.9%) 2/3 (66.7%) 0/1 (0%)
Blood and lymphatic system disorders
Anaemia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/7 (14.3%) 2 0/3 (0%) 0 0/1 (0%) 0
Cardiac disorders
Atrial fibrillation 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Atrial flutter 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Endocrine disorders
Hypothyroidism 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Gastrointestinal disorders
Abdominal pain 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 2 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Ascites 2/8 (25%) 3 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Diarrhoea 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Nausea 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Retroperitoneal haemorrhage 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Vomiting 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
General disorders
Asthenia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 2 1/3 (33.3%) 1 0/1 (0%) 0
Oedema peripheral 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Infections and infestations
Gastroenteritis 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Infection 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Lung infection 0/8 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pleural infection 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pneumonia 2/8 (25%) 2 1/6 (16.7%) 1 0/3 (0%) 0 2/7 (28.6%) 2 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Sepsis 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Skin infection 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Wound infection 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0
Investigations
Platelet count decreased 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Metabolism and nutrition disorders
Dehydration 0/8 (0%) 0 1/6 (16.7%) 1 1/3 (33.3%) 1 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Hypercalcaemia 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0
Hypokalaemia 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Malnutrition 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Muscular weakness 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Pain in extremity 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0
Nervous system disorders
Encephalopathy 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Myoclonus 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Psychiatric disorders
Delirium 0/8 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Mental status changes 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Renal and urinary disorders
Acute kidney injury 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Obstructive uropathy 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Reproductive system and breast disorders
Scrotal swelling 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion 0/8 (0%) 0 1/6 (16.7%) 2 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pleuritic pain 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pneumonitis 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pulmonary embolism 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Vascular disorders
Deep vein thrombosis 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Other (Not Including Serious) Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/8 (75%) 6/6 (100%) 3/3 (100%) 7/7 (100%) 6/6 (100%) 7/7 (100%) 7/7 (100%) 3/3 (100%) 1/1 (100%)
Blood and lymphatic system disorders
Anaemia 2/8 (25%) 3 2/6 (33.3%) 3 2/3 (66.7%) 3 2/7 (28.6%) 3 1/6 (16.7%) 2 1/7 (14.3%) 1 2/7 (28.6%) 2 1/3 (33.3%) 1 1/1 (100%) 1
Cardiac disorders
Sinus tachycardia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 1/7 (14.3%) 2 1/3 (33.3%) 1 0/1 (0%) 0
Gastrointestinal disorders
Abdominal pain 1/8 (12.5%) 1 0/6 (0%) 0 1/3 (33.3%) 2 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 2/7 (28.6%) 2 0/3 (0%) 0 0/1 (0%) 0
Constipation 1/8 (12.5%) 3 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 3/6 (50%) 3 3/7 (42.9%) 3 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Diarrhoea 0/8 (0%) 0 2/6 (33.3%) 2 1/3 (33.3%) 2 4/7 (57.1%) 9 1/6 (16.7%) 1 1/7 (14.3%) 1 3/7 (42.9%) 3 0/3 (0%) 0 0/1 (0%) 0
Gastrooesophageal reflux disease 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Nausea 3/8 (37.5%) 4 2/6 (33.3%) 3 1/3 (33.3%) 1 4/7 (57.1%) 5 3/6 (50%) 5 2/7 (28.6%) 2 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Vomiting 1/8 (12.5%) 1 1/6 (16.7%) 3 1/3 (33.3%) 1 3/7 (42.9%) 3 2/6 (33.3%) 2 2/7 (28.6%) 2 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
General disorders
Asthenia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 2/7 (28.6%) 2 0/7 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0
Chills 2/8 (25%) 2 0/6 (0%) 0 1/3 (33.3%) 1 3/7 (42.9%) 3 0/6 (0%) 0 2/7 (28.6%) 2 2/7 (28.6%) 2 0/3 (0%) 0 0/1 (0%) 0
Fatigue 3/8 (37.5%) 5 2/6 (33.3%) 2 3/3 (100%) 5 4/7 (57.1%) 6 4/6 (66.7%) 4 3/7 (42.9%) 3 3/7 (42.9%) 4 1/3 (33.3%) 3 1/1 (100%) 2
Influenza like illness 2/8 (25%) 3 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Non-cardiac chest pain 0/8 (0%) 0 2/6 (33.3%) 2 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Oedema peripheral 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 2/7 (28.6%) 2 2/6 (33.3%) 2 1/7 (14.3%) 1 1/7 (14.3%) 1 1/3 (33.3%) 1 1/1 (100%) 1
Pyrexia 1/8 (12.5%) 2 2/6 (33.3%) 2 2/3 (66.7%) 2 2/7 (28.6%) 2 0/6 (0%) 0 3/7 (42.9%) 3 2/7 (28.6%) 4 0/3 (0%) 0 0/1 (0%) 0
Infections and infestations
Bronchitis 0/8 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Urinary tract infection 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 2 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/7 (14.3%) 2 0/3 (0%) 0 0/1 (0%) 0
Investigations
Alanine aminotransferase increased 1/8 (12.5%) 3 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 1/7 (14.3%) 1 1/7 (14.3%) 3 0/3 (0%) 0 0/1 (0%) 0
Aspartate aminotransferase increased 1/8 (12.5%) 3 0/6 (0%) 0 0/3 (0%) 0 3/7 (42.9%) 4 1/6 (16.7%) 1 1/7 (14.3%) 1 1/7 (14.3%) 1 0/3 (0%) 0 1/1 (100%) 2
Blood alkaline phosphatase increased 0/8 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 2 1/7 (14.3%) 2 2/6 (33.3%) 2 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Blood creatinine increased 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 4 2/6 (33.3%) 2 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Gamma-glutamyltransferase increased 1/8 (12.5%) 2 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 2/6 (33.3%) 2 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Metabolism and nutrition disorders
Decreased appetite 1/8 (12.5%) 2 3/6 (50%) 3 1/3 (33.3%) 3 3/7 (42.9%) 4 2/6 (33.3%) 2 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Dehydration 1/8 (12.5%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1 1/7 (14.3%) 1 1/6 (16.7%) 1 1/7 (14.3%) 1 2/7 (28.6%) 2 0/3 (0%) 0 0/1 (0%) 0
Hypercalcaemia 2/8 (25%) 3 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Hyperglycaemia 2/8 (25%) 2 0/6 (0%) 0 1/3 (33.3%) 3 1/7 (14.3%) 1 1/6 (16.7%) 4 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Hyperkalaemia 0/8 (0%) 0 0/6 (0%) 0 2/3 (66.7%) 2 0/7 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Hyperuricaemia 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 1/1 (100%) 1
Hypoalbuminaemia 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 1/7 (14.3%) 2 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Hypokalaemia 1/8 (12.5%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1 2/7 (28.6%) 2 1/6 (16.7%) 1 1/7 (14.3%) 1 1/7 (14.3%) 1 1/3 (33.3%) 2 0/1 (0%) 0
Hypomagnesaemia 1/8 (12.5%) 1 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 1/7 (14.3%) 1 1/7 (14.3%) 1 1/3 (33.3%) 1 0/1 (0%) 0
Hyponatraemia 1/8 (12.5%) 1 1/6 (16.7%) 1 1/3 (33.3%) 2 3/7 (42.9%) 3 2/6 (33.3%) 2 0/7 (0%) 0 2/7 (28.6%) 2 0/3 (0%) 0 0/1 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia 1/8 (12.5%) 5 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 3 1/7 (14.3%) 1 2/7 (28.6%) 3 0/3 (0%) 0 0/1 (0%) 0
Back pain 0/8 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 2 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Bone pain 2/8 (25%) 2 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 2 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Myalgia 1/8 (12.5%) 2 2/6 (33.3%) 2 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 2/7 (28.6%) 2 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Pain in extremity 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 2/7 (28.6%) 2 1/3 (33.3%) 2 0/1 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare 2/8 (25%) 2 1/6 (16.7%) 1 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Tumour pain 2/8 (25%) 2 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Nervous system disorders
Dizziness 1/8 (12.5%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1 0/7 (0%) 0 2/6 (33.3%) 3 2/7 (28.6%) 2 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Headache 3/8 (37.5%) 3 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 3/6 (50%) 3 1/7 (14.3%) 1 2/7 (28.6%) 2 0/3 (0%) 0 1/1 (100%) 1
Neuropathy peripheral 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Psychiatric disorders
Anxiety 0/8 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/7 (0%) 0 1/3 (33.3%) 1 1/1 (100%) 3
Insomnia 1/8 (12.5%) 1 1/6 (16.7%) 1 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/7 (0%) 0 1/7 (14.3%) 1 0/3 (0%) 0 1/1 (100%) 2
Respiratory, thoracic and mediastinal disorders
Cough 1/8 (12.5%) 1 1/6 (16.7%) 1 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 2/7 (28.6%) 2 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Dyspnoea 0/8 (0%) 0 2/6 (33.3%) 5 1/3 (33.3%) 2 0/7 (0%) 0 1/6 (16.7%) 1 2/7 (28.6%) 2 1/7 (14.3%) 1 0/3 (0%) 0 1/1 (100%) 1
Oropharyngeal pain 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Pleural effusion 0/8 (0%) 0 1/6 (16.7%) 2 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Skin and subcutaneous tissue disorders
Hyperhidrosis 1/8 (12.5%) 1 0/6 (0%) 0 0/3 (0%) 0 2/7 (28.6%) 2 0/6 (0%) 0 2/7 (28.6%) 2 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Night sweats 2/8 (25%) 2 1/6 (16.7%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/1 (0%) 0
Pruritus 3/8 (37.5%) 3 0/6 (0%) 0 1/3 (33.3%) 2 3/7 (42.9%) 3 3/6 (50%) 3 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Rash 2/8 (25%) 2 0/6 (0%) 0 1/3 (33.3%) 2 2/7 (28.6%) 2 1/6 (16.7%) 1 1/7 (14.3%) 1 0/7 (0%) 0 0/3 (0%) 0 1/1 (100%) 1
Rash maculo-papular 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0
Rash pruritic 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 0/7 (0%) 0 1/3 (33.3%) 2 0/1 (0%) 0
Vascular disorders
Hypotension 0/8 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 1/7 (14.3%) 2 1/7 (14.3%) 1 0/3 (0%) 0 0/1 (0%) 0

Limitations/Caveats

The study was terminated early at the Sponsor's discretion.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Results Point of Contact

Name/Title Victoria Chiou
Organization MedImmune, LLC
Phone 301-398-4330
Email chiouv@MedImmune.com
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02205333
Other Study ID Numbers:
  • D4981C00001
First Posted:
Jul 31, 2014
Last Update Posted:
Jun 28, 2017
Last Verified:
Jun 1, 2017