Phase 2
N=183
Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01446159 ↗Enrolled (actual)
183
Serious AEs
21.3%
Results posted
Aug 2018
Primary outcome: Primary: Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) — 3; 3; 90; 82 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MEDI-573 (Drug); Aromatase Inhibitor (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- MedImmune LLC
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
3; 3; 90; 82; 2; 0 | — |
| PRIMARY Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) |
0; 0; 0 | — |
| PRIMARY Phase 1b: Number of DLTs |
0; 0; 0 | — |
| PRIMARY Phase 2: Progression-free Survival (PFS) |
12.65; 11.33 | 0.86 |
| SECONDARY Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs |
1; 1; 17; 10; 0; 0 | — |
| SECONDARY Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs |
1; 0; 1; 1; 1; 0 | — |
| SECONDARY Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs |
1; 0; 2; 0; 0; 0 | — |
| SECONDARY Phase 2: Number of Participants With Best Overall Tumor Response |
1; 2; 23; 21; 48; 46 | — |
| SECONDARY Phase 2: Objective Response Rate (ORR) |
27.0; 27.1 | — |
| SECONDARY Phase 2: Time to Response |
4.22; 3.98 | — |
| SECONDARY Phase 2: Duration of Response (DR) |
14.55; 17.18 | — |
| SECONDARY Phase 2: Time to Progression (TTP) |
14.39; 11.33 | — |
| SECONDARY Phase 2: Overall Survival (OS) |
39.39; 38.34 | — |
| SECONDARY Phase 2: Change in Tumor Size |
-36.2; -26.8 | — |
| SECONDARY 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 |
1430; 4500; 7990 | — |
| SECONDARY 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 |
1500; 4930; 9570 | — |
| SECONDARY 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 |
150; 164; 213 | — |
| SECONDARY Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1 |
269; 624; 1070 | — |
| SECONDARY Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1 |
0.04; 0.07; 0.07 | — |
| SECONDARY Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1 |
8.29; 6.17; 4.96 | — |
| SECONDARY Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1 |
4.38; 5.91; 8.45 | — |
| SECONDARY Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II |
2.57; 1.25; 3.49; 1.89; 3.81; 3.07 | — |
| SECONDARY Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573 |
0; 0; 1 | — |
Summary
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.
Eligibility Criteria
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
- Karnofsky Performance Status ≥ 70
- Life expectancy of ≥ 6 months
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT01446159). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.