Phase I Study of U3P1287/01, Including Patients With Advanced Solid Tumors

A Phase I, Open-label, Dose-Finding Study to Assess the Safety and Tolerability of U3-1287 (AMG 888), a Human Monoclonal Antibody Targeting HER3 in Patients With Advanced Solid Tumors.

This is a Phase 1 clinical study to investigate the safety, pharmacokinetics, and pharmacodynamics of U3-1287 (AMG 888), a fully human monoclonal antibody targeting the HER3 receptor, in patients with advanced solid tumors. Eligible patients will have disease that is refractory or resistant to standard treatments or for which no standard therapy exists. The study will be conducted in two parts; a dose escalation (Part 1) and a dose expansion (Part 2). The hypothesis for this study is that U3-1287 (AMG888) will be safe and well tolerated in patients with advanced solid tumors and will show initial evidence of anti-tumor activity.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: U3-1287 (AMG888)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Faber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Centre
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram cancer Centre
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Pathologically or cytologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or the patient refuses standard therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Men or women at least 18 years of age
• Adequate hematologic, cardiac, renal, hepatic, metabolic, and coagulation function

Key Exclusion Criteria:

• Presence of untreated or symptomatic brain metastasis.
• Presence of ascites or pleural effusion requiring chronic medical intervention.
• Uncontrolled hypertension
• Concurrent or previous (within 1 week of study day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low dose,low molecular weight heparin for prophylaxis against central venous catheter thrombosis.
• Recent major surgical procedure or not yet recovered from major surgery
• Recent participation in clinical drug trials.
• Participation in other investigational procedures.
• Unresolved toxicities from prior anti-cancer therapy
• Patient who is pregnant (e.g. positive human choriogonadotropin [HCG] test) or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: U3-1287 (AMG888); IV Infusion Dose Escalation (Part 1) - 5 Dose Cohorts Dose Expansion (Part 2) - 30 patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of U3-1287 (AMG888) in patients with advanced solid tumors	Lenth of study
To evaluate maximum tolerated dose (MTD) of U3-1287(AMG888) when administered intravenously to patients with advanced solid tumors	Lenth of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Parameters	Length of study
Pharmacodynamic Parameters	Length of study
Human anti-human antibody profile for U3-1287(AMG888)	Length of study

Collaborators and Investigators

• Sponsor: U3 Pharma GmbH

Publications and helpful links

General Publications

• LoRusso P, Janne PA, Oliveira M, Rizvi N, Malburg L, Keedy V, Yee L, Copigneaux C, Hettmann T, Wu CY, Ang A, Halim AB, Beckman RA, Beaupre D, Berlin J. Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2013 Jun 1;19(11):3078-87. doi: 10.1158/1078-0432.CCR-12-3051. Epub 2013 Apr 16.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 7, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 8, 2008

Study Record Updates

• Last Update Posted (Estimate): July 29, 2010
• Last Update Submitted That Met QC Criteria: July 28, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: Solid Tumors; HER3; Phase I Clinical Study; Heregulin; Human Epidermal Growth Factor Receptor 3; erb B3
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: U3P1287/01