Related Experiment Video

Updated: May 24, 2026

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
04:04

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Published on: February 12, 2017

Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors

Christina M Annunziata1, Elise C Kohn, Patricia LoRusso

  • 1Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 12 N226, Bethesda, MD 20892-1906, USA. annunzic@mail.nih.gov

Investigational New Drugs
|February 29, 2012
PubMed
Abstract

Insights

MEDI-547, an antibody drug conjugate targeting EphA2, showed concerning bleeding and liver toxicity in a phase 1 trial for solid tumors. The safety profile indicates it is not suitable for further clinical investigation.

Area of Science:

  • Oncology
  • Pharmacology
  • Immunotherapy

Background:

  • EphA2 receptor tyrosine kinase is a promising target in solid tumors.
  • Antibody drug conjugates (ADCs) offer targeted cancer therapy.
  • MEDI-547 is an ADC targeting EphA2 with an auristatin payload.

Purpose of the Study:

  • Evaluate the safety and tolerability of MEDI-547.
  • Determine the maximum tolerated dose (MTD).
  • Assess pharmacokinetics and antitumor activity of MEDI-547 in relapsed/refractory solid tumors.

Main Methods:

  • Phase 1, open-label, dose-escalation study.
  • Patients received MEDI-547 (0.08 mg/kg) intravenously every 3 weeks.
  • Safety, MTD, pharmacokinetics, and antitumor response were assessed.

Main Results:

  • The study was halted due to severe bleeding and coagulation events at 0.08 mg/kg.
  • All six patients discontinued treatment due to toxicity or disease progression.
  • Frequent adverse events included liver enzyme elevation and decreased hemoglobin; 50% experienced serious adverse events.

Conclusions:

  • The safety profile of MEDI-547 precludes further clinical development in advanced solid tumors.
  • Significant treatment-related bleeding and coagulation events were observed.
  • The MTD could not be established due to early study termination.

More Related Videos

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver09:02

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Published on: July 31, 2016

Related Concept Videos

Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
Bioavailability Study Design: Healthy Subjects Versus Patients01:15

Bioavailability Study Design: Healthy Subjects Versus Patients

Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
Preclinical Development: Overview01:28

Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...