Advanced Solid TumorsPhase 1/2MEDI6469NCT02205333

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

A Phase 1/2 study testing MEDI6469 Monotherapy, MEDI6469 Plus Tremelimumab and MEDI6469 Plus Durvalumab in people with Advanced Solid Tumors and Aggressive B-cell Lymphomas, run by MedImmune LLC at 13 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Advanced Solid Tumors, Aggressive B-cell Lymphomas
What is being tested?: MEDI6469 Monotherapy, MEDI6469 Plus Tremelimumab and MEDI6469 Plus Durvalumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 13 sitesUnited States
Study dates: 13 Aug 2014to 8 Apr 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

Research Site
Chicago, Illinois, 60611
Research Site
Detroit, Michigan, 48202
Research Site
Hackensack, New Jersey, 7601
Research Site
Houston, Texas, 77030
Research Site
Huntersville, North Carolina, 28078
Research Site
Las Vegas, Nevada, 89169
Research Site
Memphis, Tennessee, 38120
Research Site
Portland, Oregon, 97213
Research Site
Sacramento, California, 95817
Research Site
Santa Monica, California, 90404
Research Site
Scottsdale, Arizona, 85259
Research Site
Tampa, Florida, 33612
Research Site
Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

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.

Conditions: Advanced Solid Tumors, Aggressive B-cell Lymphomas
Being tested: MEDI6469 Monotherapy, MEDI6469 Plus Tremelimumab, MEDI6469 Plus Durvalumab, MEDI6469 plus Rituximab
Keywords: Advanced Solid tumors, Diffuse Large B-cell Lymphoma, programmed death 1, programmed dealth ligand 1, cytotoxic T-lymphocyte-associated antigen-4, OX40 ligand
Medical subject headings: Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MEDI6469 MonotherapyBiological
single intravenous (IV) administration of MEDI6469
MEDI6469 Plus TremelimumabBiological
MEDI6469 in combination with Tremelimumab
MEDI6469 Plus DurvalumabBiological
MEDI6469 in combination with Durvalumab
MEDI6469 plus RituximabBiological
MEDI6469 in combination with Rituximab

Study groups in NCT02205333
Study group	Role	What they receive
MEDI6469 6 mg/kg	Experimental	Participants received MEDI6469 6 milligram/kilogram (mg/kg) as a single intravenous (IV) administration on Day 1 Receives: Biological: MEDI6469 Monotherapy
MEDI6469 10 mg/kg	Experimental	Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 Receives: Biological: MEDI6469 Monotherapy
MEDI6469 2 mg/kg+Tremelimumab 3 mg/k	Experimental	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 Receives: Biological: MEDI6469 Plus Tremelimumab
MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg	Experimental	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) Receives: Biological: MEDI6469 Plus Tremelimumab
MEDI6469 2 mg/kg+Durvalumab 3 mg/kg	Experimental	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 Receives: Biological: MEDI6469 Plus Durvalumab
MEDI6469 2 mg/kg+Durvalumab 10 mg/kg	Experimental	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 Receives: Biological: MEDI6469 Plus Durvalumab
MEDI6469 10 mg/kg+Durvalumab 10 mg/kg	Experimental	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 Receives: Biological: MEDI6469 Plus Durvalumab
MEDI6469 2 mg/kg+Rituximab 375 mg/m^2	Experimental	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 Receives: Biological: MEDI6469 plus Rituximab
MEDI6469 10 mg/kg+Rituximab 375 mg/m^2	Experimental	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 Receives: Biological: MEDI6469 plus Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose (MTD) of MEDI6469
The MTD was the highest dose within a cohort where no more than 1 out of 6 participants experienced dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD.
Measured: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
Number of Participants With DLTs
The DLT was any Grade 3 or higher treatment-related toxicity (including liver transaminase elevation higher than 8×upper limit of normal [ULN] or total bilirubin higher than 5×ULN; any >=Grade 2 pneumonitis that did not resolve to <=Grade 1 within 3 days) that occurred during the DLT time frame, and excluded the following: Grade 3 fatigue for less than or equal to (<=) 7 days; Grade 3 endocrinopathy that was managed and the participant was asymptomatic; Grade 3 inflammatory reaction attributed to a local antitumor response that resolved to <=Grade 1 within 30 days; concurrent vitiligo or alopecia of any grade; Grade 3 infusion-related reaction that resolved within 6 hours; and any more than or equal to (>=) Grade 3 lymphopenia (unless clinically significant).
Measured: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs were events present at baseline that worsened in intensity after administration of study treatment or events absent at baseline that emerged after administration of study treatment.
Measured: 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)
Number of Participants With Treatment-emergent Serious Adverse Events
A serious adverse event (SAE) was any AE that resulted in death, immediately life threatening, required (or prolonged) inpatient (or existing) hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect in offspring of the participant, or an important medical event that could jeopardize the participant or required medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs present at baseline that worsened in intensity after administration of study treatment or SAEs absent at baseline that emerged after administration of study treatment.
Measured: 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)
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell [WBC] count with differential, red blood cell [RBC] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume [MCV], and mean corpuscular hemoglobin concentration [MCHC]); serum chemistry (calcium, chloride, magnesium, creatinine, sodium, blood urea nitrogen [BUN], bicarbonate, glucose, aspartate transaminase [AST], total bilirubin, C-reactive protein, gamma-glutamyl transpeptidase [GGT], lactate dehydrogenase, uric acid, potassium, alanine transaminase [ALT], alkaline phosphatase, albumin, total protein, triglycerides, and cholesterol); urinalysis; and coagulation parameters.
Measured: 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)
Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs
Vital signs examination included assessment of temperature, blood pressure, pulse rate, and respiratory rate. Physical examination included assessments of head, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems. The TEAEs related to these vital sign and physical examination abnormalities were reported.
Measured: 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)
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Electrocardiogram (ECG) parameters included atrial rate, PR interval, QRS duration, QTC interval, QT interval, and ventricular rate. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to these ECG evaluation abnormalities were reported.
Measured: 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)

Secondary outcomes (11)

Best Overall Response (BOR)
Best overall response: Percentage (%) of participants with CR, partial response (PR), stable disease (SD), progressive disease (PD), or non-evaluable disease based on revised Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Per RECIST v1.1: CR-disappearance of all target/non-target lesions; PR at least a 30% decrease in sum of diameters of target lesions; SD-neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD-at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Per Cheson criteria: CR-disappearance of all evidence of disease; PR-regression of measurable disease and no new sites; SD-failure to attain CR/PR or PD; PD-any new lesion or increase by at least 50% of previously involved sites from nadir.
Measured: From study entry until early termination (up to 1 year)
Objective Response Rate (ORR)
Objective response rate was defined as the percentage of participants with confirmed CR or confirmed PR according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Confirmed CR and PR were those that persisted on repeat consecutive assessment >= 4 weeks after the initial documentation of response. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR - disappearance of all target/non-target lesions; PR - at least a 30% decrease in the sum of the diameters of target lesions. Tumor assessments according to Cheson criteria were defined as follows: CR - disappearance of all evidence of disease; PR- regression of measurable disease and no new sites.
Measured: From study entry until early termination (up to 1 year)
Disease Control Rate
Disease control rate: Percentage of participants with CR, PR, or SD (if they maintained SD for >= 8 weeks) according to revised RECIST v1.1 for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. Tumor assessments according to revised RECIST v1.1 were defined as follows: CR -disappearance of all target/non-target lesions; PR - at least a 30% decrease in sum of diameters of target lesions; SD - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD - at least a 20% increase in sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. Tumor assessments according to Cheson criteria were defined as follows: CR- disappearance of all evidence of disease; PR - regression of measurable disease and no new sites; SD- failure to attain CR/PR or PD; PD- any new lesion or increase by at least 50% of previously involved sites from nadir.
Measured: From study entry until early termination (up to 1 year)
Duration of Response (DOR)
Duration of response was the duration from the first documented objective response to the first documented PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir.
Measured: From Study entry until early termination (up to 1 year)
Progression-free Survival (PFS)
Progression-free survival was the duration measured from the start of study treatment until the first documentation of PD or death due to any cause, whichever occurred first. Progression was based on revised RECIST v1.1 criteria for monotherapy and combination tremelimumab and durvalumab arms, and Cheson criteria for combination rituximuab arms. PD according to revised RECIST v1.1 was defined as: at least a 20% increase in the sum of diameters of target lesions, or a substantial worsening in a non-target lesion, or the appearance of new lesions. PD per Cheson criteria was defined as: any new lesion or increase by at least 50% of previously involved sites from nadir.
Measured: From Study entry until early termination (up to 1 year)
Overall Survival (OS)
The OS was the duration from the start of study treatment until death due to any cause.
Measured: From Study entry until early termination (up to 1 year)
Maximum Observed Serum Concentration (Cmax)
The pharmacokinetics (PK) parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Measured: 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
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Measured: 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.
Systemic Clearance (CL)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Measured: 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.
Terminal Phase Elimination Half-Life (T1/2)
The PK parameter was estimated using the non-compartmental analysis methods, based on the participant serum concentration-time data. The concentration-time curve was the result of blood sampling at specified time points and its measured concentration of MEDI6469
Measured: 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.
Number of Participants Positive for Human Anti-mouse Antibodies (HAMA)
The number of participants who developed detectable HAMA are presented. ImmuSTRIP® HAMA IgG ELISA Test System was used for detection, confirmation, and titration of HAMA in human serum with a HAMA positivity cut-off level of 74 nanogram per millilitre (ng/mL).
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Aug 20148 Apr 2016

First posted31 Jul 2014 (estimated)
Study start13 Aug 2014
Primary completion8 Apr 2016
Study completion8 Apr 2016

Why it stopped: The study was terminated early at the sponsor's discretion.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02205333
Sponsor's protocol ID: D4981C00001
Acronym: MEDI6469
Status last verified: Jun 2017
First submitted: 18 Jul 2014
Last updated: 28 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02205333
Acronym / sponsor ID: MEDI6469 / D4981C00001
Conditions: Advanced Solid Tumors, Aggressive B-cell Lymphomas
Keywords: Advanced Solid tumors, Diffuse Large B-cell Lymphoma, programmed death 1, programmed dealth ligand 1, cytotoxic T-lymphocyte-associated antigen-4, OX40 ligand
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated early at the sponsor's discretion.
Enrolment: 48 participants (actual)
Lead sponsor: MedImmune LLCIndustry (pharma, biotech, devices)
Study start: 13 Aug 2014 (actual)
Primary completion: 8 Apr 2016 (actual)
Study completion: 8 Apr 2016 (actual)
First posted: 31 Jul 2014 (estimated)
Results: Posted 8 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 9

Arm	Type	Receives
MEDI6469 6 mg/kg	Experimental	Biological: MEDI6469 MonotherapyParticipants received MEDI6469 6 milligram/kilogram (mg/kg) as a single intravenous (IV) administration on Day 1
MEDI6469 10 mg/kg	Experimental	Biological: MEDI6469 MonotherapyParticipants received MEDI6469 10 mg/kg as a single IV administration on Day 1
MEDI6469 2 mg/kg+Tremelimumab 3 mg/k	Experimental	Biological: MEDI6469 Plus TremelimumabParticipants 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
MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg	Experimental	Biological: MEDI6469 Plus TremelimumabParticipants 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)
MEDI6469 2 mg/kg+Durvalumab 3 mg/kg	Experimental	Biological: MEDI6469 Plus DurvalumabParticipants 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
MEDI6469 2 mg/kg+Durvalumab 10 mg/kg	Experimental	Biological: MEDI6469 Plus DurvalumabParticipants 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
MEDI6469 10 mg/kg+Durvalumab 10 mg/kg	Experimental	Biological: MEDI6469 Plus DurvalumabParticipants 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
MEDI6469 2 mg/kg+Rituximab 375 mg/m^2	Experimental	Biological: MEDI6469 plus RituximabParticipants 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
MEDI6469 10 mg/kg+Rituximab 375 mg/m^2	Experimental	Biological: MEDI6469 plus RituximabParticipants 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

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MEDI6469 Monotherapysingle intravenous (IV) administration of MEDI6469	Biological	MEDI6469 10 mg/kg, MEDI6469 6 mg/kg
MEDI6469 Plus TremelimumabMEDI6469 in combination with Tremelimumab	Biological	MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg, MEDI6469 2 mg/kg+Tremelimumab 3 mg/k
MEDI6469 Plus DurvalumabMEDI6469 in combination with Durvalumab	Biological	MEDI6469 10 mg/kg+Durvalumab 10 mg/kg, MEDI6469 2 mg/kg+Durvalumab 10 mg/kg, MEDI6469 2 mg/kg+Durvalumab 3 mg/kg
MEDI6469 plus RituximabMEDI6469 in combination with Rituximab	Biological	MEDI6469 10 mg/kg+Rituximab 375 mg/m^2, MEDI6469 2 mg/kg+Rituximab 375 mg/m^2

Primary outcome

Maximum Tolerated Dose (MTD) of MEDI6469
Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
The MTD was the highest dose within a cohort where no more than 1 out of 6 participants experienced dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD.
Number of Participants With DLTs
Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
The DLT was any Grade 3 or higher treatment-related toxicity (including liver transaminase elevation higher than 8×upper limit of normal [ULN] or total bilirubin higher than 5×ULN; any >=Grade 2 pneumonitis that did not resolve to <=Grade 1 within 3 days) that occurred during the DLT time frame, and excluded the following: Grade 3 fatigue for less than or equal to (<=) 7 days; Grade 3 endocrinopathy that was managed and the participant was asymptomatic; Grade 3 inflammatory reaction attributed to a local antitumor response that resolved to <=Grade 1 within 30 days; concurrent vitiligo or alopecia of any grade; Grade 3 infusion-related reaction that resolved within 6 hours; and any more than or equal to (>=) Grade 3 lymphopenia (unless clinically significant).
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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)
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs were events present at baseline that worsened in intensity after administration of study treatment or events absent at baseline that emerged after administration of study treatment.
Number of Participants With Treatment-emergent Serious Adverse Events
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)
A serious adverse event (SAE) was any AE that resulted in death, immediately life threatening, required (or prolonged) inpatient (or existing) hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect in offspring of the participant, or an important medical event that could jeopardize the participant or required medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs present at baseline that worsened in intensity after administration of study treatment or SAEs absent at baseline that emerged after administration of study treatment.
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
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)
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell [WBC] count with differential, red blood cell [RBC] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume [MCV], and mean corpuscular hemoglobin concentration [MCHC]); serum chemistry (calcium, chloride, magnesium, creatinine, sodium, blood urea nitrogen [BUN], bicarbonate, glucose, aspartate transaminase [AST], total bilirubin, C-reactive protein, gamma-glutamyl transpeptidase [GGT], lactate dehydrogenase, uric acid, potassium, alanine transaminase [ALT], alkaline phosphatase, albumin, total protein, triglycerides, and cholesterol); urinalysis; and coagulation parameters.
Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs
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)
Vital signs examination included assessment of temperature, blood pressure, pulse rate, and respiratory rate. Physical examination included assessments of head, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems. The TEAEs related to these vital sign and physical examination abnormalities were reported.
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
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)
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.

11 secondary outcomes

Best Overall Response (BOR)
Time frame: From study entry until early termination (up to 1 year)
Objective Response Rate (ORR)
Time frame: From study entry until early termination (up to 1 year)
Disease Control Rate
Time frame: From study entry until early termination (up to 1 year)
Duration of Response (DOR)
Time frame: From Study entry until early termination (up to 1 year)
Progression-free Survival (PFS)
Time frame: From Study entry until early termination (up to 1 year)
Overall Survival (OS)
Time frame: From Study entry until early termination (up to 1 year)
Maximum Observed Serum Concentration (Cmax)
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
Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
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.
Systemic Clearance (CL)
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.
Terminal Phase Elimination Half-Life (T1/2)
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.
Number of Participants Positive for Human Anti-mouse Antibodies (HAMA)
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)

Results and safety

Results posted to the registry on 8 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MEDI6469 6 Milligram/Kilogram (mg/kg)	8	2
MEDI6469 10 mg/kg	6	0
MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg	3	1
MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg	7	0
MEDI6469 2 mg/kg+Durvalumab 3 mg/kg	6	1
MEDI6469 2 mg/kg+Durvalumab 10 mg/kg	7	4
MEDI6469 10 mg/kg+Durvalumab 10 mg/kg	7	2
MEDI6469 2 mg/kg+Rituximab 375 mg/m^2	3	1
MEDI6469 10 mg/kg+Rituximab 375 mg/m^2	1	1

Primary outcome: Maximum Tolerated Dose (MTD) of MEDI6469

Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days). Number. Unit: milligram per kilogram (mg/kg)

Measure	MEDI6469 6 mg/kg n = 8	MEDI6469 10 mg/kg n = 6	MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg n = 3	MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+Durvalumab 3 mg/kg n = 6	MEDI6469 2 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 10 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 n = 3	MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 n = 1
Value	NA	NA	NA	NA	NA	NA	NA	NA	NA

Population analysed: 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.

Primary outcome: Number of Participants With DLTs

Time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days). Number. Unit: Participant

Measure	MEDI6469 6 mg/kg n = 8	MEDI6469 10 mg/kg n = 6	MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg n = 3	MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+Durvalumab 3 mg/kg n = 6	MEDI6469 2 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 10 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 n = 3	MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 n = 1
Value	0	0	0	1	1	1	0	0	0

Population analysed: DLT-evaluable population

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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). Number. Unit: Participant

Measure	MEDI6469 6 mg/kg n = 8	MEDI6469 10 mg/kg n = 6	MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg n = 3	MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+Durvalumab 3 mg/kg n = 6	MEDI6469 2 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 10 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 n = 3	MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 n = 1
Value	8	6	3	7	6	7	7	3	1

Population analysed: As-treated population: all the participants who received any study treatment.

Primary outcome: Number of Participants With Treatment-emergent Serious 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). Number. Unit: Participant

Measure	MEDI6469 6 mg/kg n = 8	MEDI6469 10 mg/kg n = 6	MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg n = 3	MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+Durvalumab 3 mg/kg n = 6	MEDI6469 2 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 10 mg/kg+Durvalumab 10 mg/kg n = 7	MEDI6469 2 mg/kg+ Rituximab 375 mg/m^2 n = 3	MEDI6469 10 mg/kg + Rituximab 375 mg/m^2 n = 1
Value	4	3	1	5	3	3	3	2	0

Population analysed: As-treated population

11 secondary outcomes are reported in the full results.

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). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MEDI6469 6 Milligram/Kilogram (mg/kg)	4 of 8 (50%)	6 of 8 (75%)	Not reported
MEDI6469 10 mg/kg	3 of 6 (50%)	6 of 6 (100%)	Not reported
MEDI6469 2 mg/kg+Tremelimumab 3 mg/kg	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg	5 of 7 (71.4%)	7 of 7 (100%)	Not reported
MEDI6469 2 mg/kg+Durvalumab 3 mg/kg	3 of 6 (50%)	6 of 6 (100%)	Not reported
MEDI6469 2 mg/kg+Durvalumab 10 mg/kg	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
MEDI6469 10 mg/kg+Durvalumab 10 mg/kg	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
MEDI6469 2 mg/kg+Rituximab 375 mg/m^2	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
MEDI6469 10 mg/kg+Rituximab 375 mg/m^2	0 of 1 (0%)	1 of 1 (100%)	Not reported

Limitations and caveats (from the sponsor): The study was terminated early at the Sponsor's discretion.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MedImmune, LLC study director

MedImmune LLC

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of MEDI6469 (time frame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02205333.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2017.