Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MEDI-575 · 3 trials · 3 indications
Progression-free survival (PFS) rate at 6 months is defined as the proportion of participants who neither progressed nor died before 6 months after the first dose. Progression was determined using Updated Response Assessment Criteria of High Grade Gliomas: Response Assessment in Neuro-Oncology Working Group (RANO criteria). Progression was defined as at least 25% increase in measurement of enhancing lesions compared with the smallest tumor measurement obtained during the study; or significant increase in T2/fluid attenuated inversion recovery (FLAIR) nonenhancing lesion compared with baseline scan or best response; or any new lesion; or clear clinical deterioration; or failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease. PFS-6 was estimated using Kaplan-Meier method.
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are 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 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
| Arm | Type | Description |
|---|---|---|
| MEDI-575, 25 mg/kg | EXPERIMENTAL | MEDI-575 administered as an intravenous infusion at 25 mg/kg over a period of 60-minutes on Day 1 of each 21-day cycle until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, or other reasons for participants withdrawal. |
| 1 | EXPERIMENTAL | - |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | EXPERIMENTAL | Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days \[QWk\]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | EXPERIMENTAL | MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | EXPERIMENTAL | MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | EXPERIMENTAL | MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | EXPERIMENTAL | MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | EXPERIMENTAL | MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days \[Q3Wk\]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | EXPERIMENTAL | MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | EXPERIMENTAL | MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | EXPERIMENTAL | MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| Name | Type | Description |
|---|---|---|
| MEDI-575 | DRUG | MEDI-575 as an IV infusion. |
Inclusion Criteria: * Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations * Age ≥18 years old at the time of screening * His...
MEDI-575 is an investigational small molecule being studied for the treatment of advanced solid malignancies, cancer, and glioblastoma multiforme. It has been evaluated in clinical trials for these oncology indications, though it remains in clinical development and is not approved.
MEDI-575 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company has sponsored clinical trials to evaluate the drug's safety and antitumor activity in patients with advanced tumors.
MEDI-575 has been studied in Phase 1 and Phase 2 clinical trials. The Phase 1 trials evaluated safety and tolerability in advanced tumors, while a Phase 2 trial assessed the drug in recurrent glioblastoma multiforme. All trials are completed, and the drug is investigational.
MEDI-575 has been involved in three completed clinical trials: NCT00816400, a Phase 1 dose escalation study in patients with advanced tumors in the United States; NCT01102400, a Phase 1 study in Japanese patients with advanced solid malignancies; and NCT01268566, a Phase 2 study in patients with recurrent glioblastoma multiforme.
MEDI-575 is a small molecule, but its specific molecular target is not disclosed in the available information. The drug has been studied for its antitumor activity in various cancer types, including glioblastoma multiforme, but the precise mechanism of action has not been detailed.