A Study of RO5479599 Alone or in Combination With Cetuximab or Erlotinib in Participants With Metastatic and/or Locally Advanced Malignant Human Epidermal Growth Factor Receptor (HER3) Expressing Solid Tumors of Epithelial Cell Origin

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Cetuximab; Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

All Parts (A, B and C)

• European Cooperative Oncology Group (ECOG) performance status 0-2

• Histologically confirmed metastatic and/or locally advanced malignant HER3-expressing solid tumors of epithelial origin

• Availability of tissue and willingness to perform fresh pretreatment biopsies

• Participants for whom no standard therapy exists

• All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade less than or equal to (Grade 2 peripheral neuropathy

• Adequate hematological, renal and liver function

• Participants with Gilbert's syndrome will be eligible for the study

Part B extension cohort: In addition to the above inclusion criteria, participants will be eligible if they have metastatic and/or locally advanced non-small cell lung cancer or squamous cell carcinoma of the head and neck or colorectal cancer (wild type with positive epidermal growth factor receptor [EGFR] expression)

Part C extension cohort: In addition to the above inclusion criteria, participants will be eligible only if they have metastatic and/or locally advanced squamous non-small cell lung cancer

Exclusion Criteria:

• Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases. History or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days

• Evidence of significant uncontrolled concomitant diseases or disorders

• Active or uncontrolled infections

• Known Human immuno deficiency virus (HIV) infection

• Therapy with antibody or immunotherapy concurrently or within 14 days prior to first dose of study drug

• Regular immunosuppressive therapy

• Concurrent high dose of systemic corticosteroids (greater than (>) 20 milligrams per day [mg/day] dexamethasone or equivalent for > 7 consecutive days)