A Phase 1b/2 Randomized Study of MEDI-573 in Combination With an Aromatase Inhibitor (AI) Versus AI Alone in Women With Metastatic Breast Cancer (MBC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
Study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an aromatase inhibitor (AI) in adult subjects with HR+, HER2-negative MBC.
详细描述
This is a Phase 1b/2, multicenter, open-label study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an AI in adult subjects with HR+, HER2-negative MBC. This study has 2 phases: a dose-evaluation phase (Phase 1b) and a randomization phase (Phase 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •Karnofsky Performance Status ≥ 70
- •Life expectancy of ≥ 6 months
排除标准
- •Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or metastatic disease with the following exceptions:
- •Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment ended at least 2 weeks prior to the first dose of MEDI-573
- •Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed
- •Extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or disease that is considered by the investigator to be rapidly progressing or life threatening (eg, subjects who are intended for chemotherapy)
- •Active brain metastases with the exception of subject has been treated and are asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of first dose of MEDI-573
- •Evidence of ongoing spinal cord compression or leptomeningeal carcinomatosis
- •Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to ≤ Grade 1 at the time of starting study treatment
- •Previous treatment with agents that target the IGF receptor
- •History of allergy or reaction attributed to compounds of chemical or biologic composition similar to those of MEDI-573 or AI
- •History of another invasive malignancy within 5 years except for curatively resected nonmelanoma skin cancer or carcinoma in situ of the cervix
- •Poorly controlled diabetes mellitus
研究组 & 干预措施
MEDI-573 10 mg/kg + AI
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.
干预措施: MEDI-573 (Drug)
MEDI-573 10 mg/kg + AI
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.
干预措施: Aromatase Inhibitor (Drug)
MEDI-573 30 mg/kg + AI
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.
干预措施: MEDI-573 (Drug)
MEDI-573 30 mg/kg + AI
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.
干预措施: Aromatase Inhibitor (Drug)
MEDI-573 45 mg/kg + AI
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.
干预措施: MEDI-573 (Drug)
MEDI-573 45 mg/kg + AI
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.
干预措施: Aromatase Inhibitor (Drug)
Aromatase Inhibitor
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.
干预措施: Aromatase Inhibitor (Drug)
结局指标
主要结局
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)
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).
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Up to Day 21 of Cycle 1
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.
Phase 1b: Number of DLTs
时间窗: Up to Day 21 of Cycle 1
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.
Phase 2: Progression-free Survival (PFS)
时间窗: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
次要结局
- Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs(From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years))
- Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs(From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years))
- Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II(Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years))
- Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs(From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years))
- Phase 2: Number of Participants With Best Overall Tumor Response(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Objective Response Rate (ORR)(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Time to Response(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Duration of Response (DR)(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Time to Progression (TTP)(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Overall Survival (OS)(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 2: Change in Tumor Size(From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years))
- Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Day 21 (AUC0-day21) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Dose-Normalised Area Under the Serum Concentration-time Curve From Time Zero to Infinity (DN AUC0-inf) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1(Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose))
- Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573(Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years))