Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MEDI-551 · 5 trials · 7 indications
ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A TEAE were the events between administration of study drug (Day 1) and Day 169 that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect in the offspring of a participant who received the study drug. The TESAEs were the events between administration of study drug (Day 1) and long term follow up period (up to 18 months after early discontinuation visit or 24-week treatment period) that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
Any clinically significant change in laboratory evaluations were recorded as AEs. The following parameters were analyzed for laboratory evaluations: haematology, serum chemistry, and urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Vital sign parameters included blood pressure, temperature, pulse rate, and respiratory rate. The number of participants with TEAEs related to vital signs in participants were reported.
Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (\<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.
Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which \<= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which \<= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are 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.
A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,\>= Grade 3 or 4 lymphopenia or leukopenia, \<= Grade 4 neutropenia, \<= Grade 4 thrombocytopenia, \<= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.
The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: \>= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: \>= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: \>= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.
Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
| Arm | Type | Description |
|---|---|---|
| Rituximab + Bendamustine | ACTIVE_COMPARATOR | Rituximab was administered by IV infusion as 375 mg/m\^2 on Day 2 of Cycle 1 and then 500 mg/m\^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle. |
| MEDI-551 2 mg/kg + Bendamustine | EXPERIMENTAL | MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle. |
| MEDI-551 4 mg/kg + Bendamustine | EXPERIMENTAL | MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle. |
| MEDI-551 30 MG-IV | EXPERIMENTAL | Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15. |
| MEDI-551 60 MG-SC | EXPERIMENTAL | Participants received SC injection of 60 mg MEDI-551 on Day 1. |
| MEDI-551 100 MG-IV | EXPERIMENTAL | Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15. |
| MEDI-551 300 MG-SC | EXPERIMENTAL | Participants received SC injection of 300 mg MEDI-551 on Day 1. |
| MEDI-551 600 MG-IV | EXPERIMENTAL | Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15. |
| PLACEBO-IV-SC | PLACEBO_COMPARATOR | Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1. |
| MEDI-551 | EXPERIMENTAL | - |
| Part A-MEDI-551 0.5 mg/kg | EXPERIMENTAL | Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 1 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 2 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 4 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 8 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part A-MEDI-551 12 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 6 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 12 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part B-MEDI-551 24 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed. |
| Part C-MEDI-551 8 mg/kg + rituximab | EXPERIMENTAL | Participants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. |
| Part C-MEDI-551 12 mg/kg + rituximab | EXPERIMENTAL | Participants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent. |
| Part D-MEDI-551 12 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent. |
| 1 | EXPERIMENTAL | MEDI-551 |
| 2 | EXPERIMENTAL | MEDI-551 |
| 3 | EXPERIMENTAL | MEWDI-551 |
| 4 | EXPERIMENTAL | MEDI-551 |
| 5 | EXPERIMENTAL | MEDI-551 |
| 6 | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| Rituximab | DRUG | Rituximab was administered by IV infusion as a dose of 375 mg/m\^2 on Day 2 of Cycle 1 and then at 500 mg/m\^2 on Day 1 of up to 5 subsequent 28-day cycles |
| Bendamustine | DRUG | Bendamustine was administered by IV infusion as a dose of 70 mg/m\^2 on Day 1 and Day 2 of each 5 subsequent 28-day cycle. |
| MEDI-551 | DRUG | MEDI-551 was administered at 2 mg/kg or 4 mg/kg by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycles. |
| MEDI-551 30 MG-IV | DRUG | Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15. |
| MEDI-551 60 MG-SC | DRUG | Participants received SC injection of 60 mg MEDI-551 on Day 1. |
| PLACEBO-IV-SC | DRUG | Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1 |
| MEDI-551 100 MG-IV | DRUG | Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15. |
| MEDI-551 300 MG-SC | DRUG | Participants received SC injection of 300 mg MEDI-551 on Day 1. |
| MEDI-551 600 MG-IV | DRUG | Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15. |
| Placebo | BIOLOGICAL | 0.3 mg/kg |
Inclusion Criteria: * Histologically confirmed B-cell Chronic Lymphocytic Leukemia (CLL) according to the National Cancer Institute criteria; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; Adequate hematological function Exclusion Criteria: * Any chemotherapy, radioth...
MEDI-551 is an investigational drug being studied for B-cell malignancies, multiple sclerosis, scleroderma, chronic lymphocytic leukemia (CLL), and relapsed or refractory aggressive B-cell lymphomas. It has been evaluated in clinical trials for these conditions, including diffuse large B-cell lymphoma and scleroderma.
MEDI-551 is being developed by AstraZeneca PLC, a biopharmaceutical company traded on the stock exchange under the ticker symbol AZN. The drug is currently in clinical development and is not approved for any indication.
MEDI-551 has completed Phase 1 and Phase 2 clinical trials. It is an investigational drug, meaning it is still in clinical development and has not been approved by regulatory authorities. Its development status is based on completed trials in various conditions.
MEDI-551 has been studied in several completed clinical trials. These include NCT00946699 for scleroderma, NCT00983619 for relapsed or refractory advanced B-cell malignancies, NCT01453205 for diffuse large B-cell lymphoma, and NCT02271945 for aggressive B-cell lymphomas in combination with immunomodulating therapies.
MEDI-551 is the primary name used for this investigational drug in clinical trials. No alternative names have been established for MEDI-551 in the available clinical trial information.