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Also known as MEDI-573 (1 of 3 doses)
MEDI-573 · 4 trials · 4 indications
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs 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 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years).
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were \>= Grade 3 in severity were considered as DLTs.
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were \>= Grade 3 in severity were considered as DLTs.
Progression-free survival (PFS) was defined as the time from the randomization until the first documentation of disease progression or death due to any cause, whichever occurred first. The PFS was censored on the date of the last tumor assessment documenting absence of tumor progression for participants who had no documented progression and were still alive prior to data cut-off, dropout, or the initiation of alternate anticancer treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as \>= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The 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 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The 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 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The 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 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The 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 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
An abnormal laboratory finding 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 MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
| Arm | Type | Description |
|---|---|---|
| MEDI-573 10 mg/kg + AI | EXPERIMENTAL | Participants who will be enrolled in Phase 1b Cohort A of the study will receive intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| MEDI-573 30 mg/kg + AI | EXPERIMENTAL | Participants who will be enrolled in Phase 1b Cohort B of the study will receive intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| MEDI-573 45 mg/kg + AI | EXPERIMENTAL | Participants who will be enrolled in Phase 1b Cohort C and Phase 2 Arm 1 of the study will receive intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| Aromatase Inhibitor | EXPERIMENTAL | Participants who will be enrolled in Phase 2 Arm 2 of the study will receive oral AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| Phase 1b Cohort A | EXPERIMENTAL | Participants will receive MEDI-573 10 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. |
| Phase 1b Cohort B | EXPERIMENTAL | Participants will receive MEDI-573 45 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. |
| Phase 1b Cohort C | EXPERIMENTAL | Participants will receive MEDI-573 30 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. |
| Phase 2 Arm 1 | EXPERIMENTAL | Participants will receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. |
| Phase 2 Arm 2 | ACTIVE_COMPARATOR | Participants will receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. |
| MEDI-573 | EXPERIMENTAL | MEDI-573 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 5 mg/Kg QWk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 10 mg/Kg QWk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 15 mg/Kg QWk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | EXPERIMENTAL | Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 5 mg/Kg QWk Dose Expansion | EXPERIMENTAL | Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| MEDI-573 15 mg/Kg QWk Dose Expansion | EXPERIMENTAL | Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. |
| Name | Type | Description |
|---|---|---|
| MEDI-573 | DRUG | Intravenous infusion of MEDI-573 (10 or 30 or 45 mg/kg) will be administered on Day 1 of each 21-day cycle until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| Aromatase Inhibitor | DRUG | Aromatase inhibitor of the investigator's choice (letrozole, anastrozole, or exemestane) will be provided orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. |
| MEDI-573 (1 of 3 doses) | DRUG | MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands |
| Sorafenib | DRUG | Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor |
Inclusion Criteria: * Histologically-confirmed MBC not deemed amenable to curative surgery or curative radiation therapy * Tumors are positive for ER, PgR, or both * Tumors must be negative for HER2 (by FISH, CISH or IHC) * Female gender and age ≥ 18 years at time of study entry * Postmenopausal * ...
MEDI-573 is an investigational small molecule developed by AstraZeneca PLC for oncology. It has been studied in advanced solid tumors, hormone-sensitive HER-2 negative metastatic breast cancer, and unresectable or metastatic hepatocellular carcinoma. It is not approved and remains in clinical development.
MEDI-573 was studied in combination with standard endocrine therapy for women with hormone-sensitive, HER-2 negative metastatic breast cancer. A Phase 2 trial, NCT01446159, enrolled 188 women across the United States, Europe, and Israel. The trial is completed, and MEDI-573 is not approved for this or any indication.
MEDI-573 is developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. AstraZeneca sponsored the clinical trials of MEDI-573 in advanced solid tumors, breast cancer, and hepatocellular carcinoma.
MEDI-573 is in Phase 1 development. It has been evaluated in Phase 1 dose-escalation studies in advanced solid tumors and in Japanese subjects, and in a Phase 2 study in hormone-sensitive, HER-2 negative metastatic breast cancer. All reported trials are completed, and no trials are currently active.
MEDI-573 has been studied in four completed trials: NCT00816361 and NCT01340040, Phase 1 dose-escalation studies in advanced solid tumors; NCT01446159, a Phase 2 study in hormone-sensitive, HER-2 negative metastatic breast cancer; and NCT01498952, a Phase 1 study in unresectable or metastatic hepatocellular carcinoma.
Yes. MEDI-573 (1 of 3 doses) refers to the same investigational compound as MEDI-573, developed by AstraZeneca PLC. The parenthetical notation indicates a specific dose level within a dose-escalation study rather than a different drug.