Phase Ia/Ib, Open-label, Multicenter, Dose-escalation Study Followed by an Extension Phase to Evaluate 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 Erlotininb (Part C) in Patients With Metastatic and/or Locally Advanced Malignant HER3-positive Solid Tumors of Ephitelian Cell Origin
Inclusion Criteria:
- Adult patients, >/= 18 years of age
- European Cooperative Oncology Group (ECOG) performance status 0-2
- Histologically confirmed metastatic and/or locally advanced malignant HER3-expressing
solid tumors of epithelian origin
- Availability of tissue and willingness to perform fresh pretreatment biopsies
- Patients for whom no standard therapy exists
- All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure
must have resolved to Grade = 1, except for alopecia and Grade 2 peripheral
neuropathy
- Adequate hematological, renal and liver function
- Patient's with Gilbert's syndrome will be eligible for the study
- Part B extension cohort: In addition to the above inclusion criteria, patients 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 EGFR expression)
- Part C extension cohort: In addition to the above inclusion criteria, patients will
be eligible only if they have metastatic and/or locally advanced non-small cell lung
cancer or pancreatic cancer
Exclusion Criteria:
- Known or clinically suspected CNS primary tumors or metastases including
leptomeningeal metastases, except for previously treated CNS metastases that are
asymptomatic and did not require steroids or enzyme-inducing anticonvulsants in the
last 14 days
- Evidence of significant uncontrolled concomitant diseases or disorders
- Active or uncontrolled infections
- Known 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 (> 20 mg/day dexamethasone or
equivalent for > 7 consecutive days)