Phase Ia/Ib, Open-Label, Multicenter, Dose-Escalation Study Followed by an Extension Phase to Evaluate the Safety, Pharmacokinetics and Activity of RO5479599, A Glycoengineered Antibody Against HER3, Administered Either Alone (Part A) or in Combination With Cetuximab (Part B) or in Combination With Erlotinib (Part C) in Patients With Metastatic and/or Locally Advanced Malignant HER3-Positive Solid Tumors of Epithelial Cell Origin

NCT01482377 Phase 1 COMPLETED

This dose-escalating study consists of 3 parts (A, B and C) and will evaluate the safety, pharmacokinetics and efficacy of RO5479599, alone or in combination with cetuximab or erlotinib, in participants with metastatic and/or locally advanced malignant HER3-positive solid tumors. Cohorts of participants will receive escalating doses of intravenous RO5479599 as monotherapy (Part A) or in combination with cetuximab (in Part B) or with erlotinib (in Part C) followed by an extension phase for each part. In an imaging substudy, participants will receive one or two doses of zirconium-89-labeled RO5479599 (89ZrRO5479599) in addition to unlabeled RO5479599 to evaluate the in vivo biodistribution and organ pharmacokinetics of RO5479599.

Details

Lead sponsor	Hoffmann-La Roche
Phase	Phase 1
Status	COMPLETED
Enrolment	145
Start date	2011-12
Completion	2016-02

Conditions

• Neoplasms

Interventions

• RO5479599
• Cetuximab
• Erlotinib
• zirconium-89-labeled RO5479599

Primary outcomes

• Percentage of Participants With Adverse Events — Baseline up to 28 days after last dose (approximately 48 months)
• Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of RO5479599 — Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
• Number of Participants With Dose Limiting Toxicities (DLTs) — Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
• Standardized Uptake Value (SUV) of 89ZrRO5479599 Determined by Positron Emission Tomography (PET) Scan Over Regions of Interest (ROI) — From baseline to Day 8

Countries

Denmark, Netherlands, South Korea, Spain