Relapsed/Refractory Aggressive B-cell Lymphomas
Conditions
Keywords
aggressive lymphoma, DLBCL, NHL
Brief summary
This is a Phase 1b/2 open-label study to evaluate the safety/efficacy of MEDI-551 + MEDI0680 in participants with relapsed or refractory aggressive B-cell lymphomas who have failed 1-2 prior lines of therapy.
Detailed description
This is a Phase 1b/2, multicenter, open-label, study of MEDI-551 in combination with immunomodulating therapy evaluating the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity in subjects with relapsed or refractory aggressive B-cell lymphomas
Interventions
DRUGMEDI-551 12 mg/kg
Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13
DRUGMEDI0680 2.5 mg/kg
Participants will receive IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
DRUGMEDI0680 10 mg/kg
Participants will receive IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: * Histologically confirmed aggressive diffuse large B-cell lymphoma (DLBCL), including follicular lymphoma (FL) transforming to DLBCL, transformed indolent lymphoma, mantle cell lymphoma (MCL), or Grade 3B FL for dose-escalation cohorts. Only participants with DLBCL will be enrolled in the dose-expansion cohort. * Willing to provide a fresh tumor sample * Evaluable/measurable disease with measurable disease defined as greater than or equal to (\>= 1) lesion less than or equal to (\<=) 20 mm in one dimension or ≥ 15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). Disease evaluable by the International Working Group criteria (Cheson et al, 2007). (NOTE: Irradiated lesions will not be evaluable.) * Baseline fludeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites. * Relapsed from or refractory to \>= 2 prior chemotherapy regimens with \>= 1 regimen containing rituximab or failed 1 prior rituximab-containing regimen and unable to tolerate additional multiagent chemotherapy. NOTE: Subjects enrolled in the dose-escalation portion of the study must have exhausted all available standard therapy. * At least 100 days past autologous stem cell transplant (ASCT). * At least 1 year past allogeneic stem-cell transplant (SCT) and off immunosuppression therapy, with no evidence of graft-versus-host disease. * Eastern Cooperative Oncology Group performance status 0-2. * Adequate hematological function * Adequate organ function * Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product. * Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1through 90 days after receipt of the final dose of investigational product. Key
Exclusion criteria
* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer. * Receipt of any experimental therapy, mAb, cancer vaccine, chemotherapy or small molecule within 28 days prior to Cycle 1 Day 1 or 5 half-lives of that therapy, whichever is shorter. * Previous therapy directed against cluster of differentiation 19 (CD19) * Prior exposure to immunotherapy such as but not limited to other anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), anti-PD 1, or anti-PD-L1 antibodies excluding cancer vaccines. * Vaccination with a live virus within 28 days prior to receiving the first dose of study drug * History of other invasive malignancy within 2 years except for cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has been surgically cured. * Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given unless the subject is clinically stable. * Human immunodeficiency virus (HIV) positive serology or acquired immunodeficiency syndrome (AIDS). * Active hepatitis B * Ongoing \>= Grade 2 toxicities from previous cancer therapies or any unresolved \> Grade 1 immune-related adverse event (irAE) event unless specifically allowed in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of MEDI-551 | Day 1 to Day 28 of Cycle 1 (28-day cycle) | The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (\<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment. |
| Number of Participants With Best Overall Response | Day 1 to Day 28 of Cycle 13 (28-day cycle) | The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Response | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Duration of Complete Response defined as time from start of first documented Complete Response \[CR\] to the time of disease progression or death, whichever occurs first. Only participants who have achieved complete response assessed by investigator were evaluated. |
| Number of Participants With Disease Control | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Disease control includes CR (disappearance of all evidence of disease), PR (regression of measurable disease and no new sites), or SD for at least 8 weeks. |
| Duration of Disease Control | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Duration of disease control is defined as the time period from the start of disease control event to the event of disease progression. |
| Mean Peak and Trough Concentrations of MEDI0680 | EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 | The mean peak and Trough concentration of MEDI0680 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement. |
| Overall Survival (OS) | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Overall survival defined as the time from the start of study drug administration until death due to any cause. |
| Time to Response (TTR) | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Time to response (TTR) defined as the time from the start of study drug administration until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR. |
| Progression-free Survival (PFS) | From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) | Progression-free survival (PFS) is defined as the time from the start of study drug administration until the first documentation of disease progression or death due to any cause, whichever occurs first. |
| Terminal Half-Life (t1/2) of MEDI551 | EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 | Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum. |
| Mean Peak and Trough Concentrations of MEDI551 | End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 | The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement. |
| Terminal Half-Life (t1/2) of MEDI0680 | EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 | Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 | 30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years) | A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study. |
Countries
United States
Participant flow
Recruitment details
The study was conducted from 01Dec2014 to 24May2016.
Pre-assignment details
A total of 16 participants were screened in this study. Of which, 6 participants failed screening and 10 participants were enrolled in the study and received the study drugs.
Participants by arm
| Arm | Count |
|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13. | 5 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13. | 5 |
| TOTAL Total of all reporting groups | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 3 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | TOTAL |
|---|---|---|---|
| Age, Continuous | 63.2 YEARS STANDARD_DEVIATION 7.1 | 63.8 YEARS STANDARD_DEVIATION 14.8 | 63.5 YEARS STANDARD_DEVIATION 11 |
| Age, Customized < 65 YEARS | 3 Participants | 3 Participants | 6 Participants |
| Age, Customized >= 65 YEARS | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 5 | 3 / 5 |
| other Total, other adverse events | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 2 / 5 | 1 / 5 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of MEDI-551
The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (\<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.
Time frame: Day 1 to Day 28 of Cycle 1 (28-day cycle)
Population: Evaluable Population for DLT included all participants in the dose escalation portion who received all protocol assigned doses and completed safety follow-up during the first 28-day period of therapy, or experienced a DLT during the DLT evaluation period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Maximum Tolerated Dose (MTD) of MEDI-551 | NA mg/kg |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Maximum Tolerated Dose (MTD) of MEDI-551 | NA mg/kg |
Primary
Number of Participants With Best Overall Response
The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE).
Time frame: Day 1 to Day 28 of Cycle 13 (28-day cycle)
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Best Overall Response | Partial Response | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Best Overall Response | Progressive Disease | 5 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Best Overall Response | Stable Disease | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Best Overall Response | Non-evaluable | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Best Overall Response | Complete Response | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Best Overall Response | Non-evaluable | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Best Overall Response | Complete Response | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Best Overall Response | Partial Response | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Best Overall Response | Stable Disease | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Best Overall Response | Progressive Disease | 3 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 5 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities
An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood pressure increased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | White blood cell count decreased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hypoglobulinaemia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyperglycaemia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Lymphocyte count decreased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyperuricaemia | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood creatinine increased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hypocalcaemia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Neutrophil count decreased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyponatraemia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood alkaline phosphatase increased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Haematuria | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Platelet count decreased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Proteinuria | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Febrile neutropenia | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Proteinuria | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Febrile neutropenia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hypoglobulinaemia | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood creatinine increased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Blood pressure increased | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Lymphocyte count decreased | 2 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Neutrophil count decreased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Platelet count decreased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | White blood cell count decreased | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyperglycaemia | 2 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyperuricaemia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hypocalcaemia | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Hyponatraemia | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities | Haematuria | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities
Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities | Infusion related reaction | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities | Pyrexia | 0 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities | Infusion related reaction | 2 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities | Pyrexia | 1 Participants |
Secondary
Duration of Complete Response
Duration of Complete Response defined as time from start of first documented Complete Response \[CR\] to the time of disease progression or death, whichever occurs first. Only participants who have achieved complete response assessed by investigator were evaluated.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.
Secondary
Duration of Disease Control
Duration of disease control is defined as the time period from the start of disease control event to the event of disease progression.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.
Secondary
Mean Peak and Trough Concentrations of MEDI0680
The mean peak and Trough concentration of MEDI0680 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Time frame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D15 Predose | 18.7 mcg/mL | Standard Deviation 2.1 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C2D1 End of Infusion | 92.9 mcg/mL | Standard Deviation 17.1 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D2 End of Infusion | 49.8 mcg/mL | Standard Deviation 18.2 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C3D1 End of Infusion | 110 mcg/mL | Standard Deviation 29.6 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D15 End of Infusion | 72.5 mcg/mL | Standard Deviation 12.4 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C4D1 Predose | 62.2 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C3D1 Predose | 44.1 mcg/mL | Standard Deviation 3.25 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C4D1 End of Infusion | 86.0 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C2D1 Predose | 32.8 mcg/mL | Standard Deviation 6.31 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C4D1 End of Infusion | 595 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D2 End of Infusion | 256 mcg/mL | Standard Deviation 101 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D15 Predose | 109 mcg/mL | Standard Deviation 30.1 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C1D15 End of Infusion | 298 mcg/mL | Standard Deviation 41.7 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C2D1 Predose | 178 mcg/mL | Standard Deviation 52.3 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C3D1 Predose | 277 mcg/mL | Standard Deviation 64.3 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C3D1 End of Infusion | 590 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C4D1 Predose | 364 mcg/mL | Standard Deviation 77.1 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI0680 | C2D1 End of Infusion | 339 mcg/mL | Standard Deviation 55.9 |
Secondary
Mean Peak and Trough Concentrations of MEDI551
The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Time frame: End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C2D1 End of Infusion | 276 mcg/mL | Standard Deviation 59.1 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C1D8 End of Infusion | 329 mcg/mL | Standard Deviation 63.4 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C3D1 Predose | 109 mcg/mL | Standard Deviation 26.8 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C1D8 Predose | 103 mcg/mL | Standard Deviation 13.3 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C3D1 End of Infusion | 325 mcg/mL | Standard Deviation 71.8 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C2D1 Predose | 92.4 mcg/mL | Standard Deviation 36.3 |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C4D1 Predose | 85.7 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C4D1 End of Infusion | 338 mcg/mL | — |
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | Cycle1 Day1 End of Infusion | 244 mcg/mL | Standard Deviation 49.3 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C4D1 End of Infusion | 292 mcg/mL | Standard Deviation 77.8 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | Cycle1 Day1 End of Infusion | 220 mcg/mL | Standard Deviation 66.2 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C1D8 Predose | 96.8 mcg/mL | Standard Deviation 38.3 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C1D8 End of Infusion | 313 mcg/mL | Standard Deviation 74.2 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C2D1 Predose | 103 mcg/mL | Standard Deviation 45.4 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C2D1 End of Infusion | 336 mcg/mL | Standard Deviation 76.1 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C3D1 Predose | 108 mcg/mL | Standard Deviation 49.9 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C3D1 End of Infusion | 300 mcg/mL | Standard Deviation 55.2 |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Mean Peak and Trough Concentrations of MEDI551 | C4D1 Predose | 111 mcg/mL | Standard Deviation 57.2 |
Secondary
Number of Participants With Disease Control
Disease control includes CR (disappearance of all evidence of disease), PR (regression of measurable disease and no new sites), or SD for at least 8 weeks.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680
A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study.
Time frame: 30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 | 1 Participants |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 | 0 Participants |
Secondary
Overall Survival (OS)
Overall survival defined as the time from the start of study drug administration until death due to any cause.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the start of study drug administration until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.
Secondary
Terminal Half-Life (t1/2) of MEDI0680
Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time frame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Terminal Half-Life (t1/2) of MEDI0680 | NA h |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Terminal Half-Life (t1/2) of MEDI0680 | NA h |
Secondary
Terminal Half-Life (t1/2) of MEDI551
Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time frame: EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
Population: As-treated Population included all participants who were treated with study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg | Terminal Half-Life (t1/2) of MEDI551 | NA h |
| MEDI-551 12 mg/kg and MEDI0680 10 mg/kg | Terminal Half-Life (t1/2) of MEDI551 | NA h |
Secondary
Time to Response (TTR)
Time to response (TTR) defined as the time from the start of study drug administration until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR.
Time frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Population: As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.