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

Roche

Status and phase

Completed

Phase 1

Conditions

Neoplasms

Treatments

Drug: Cetuximab

Drug: zirconium-89-labeled RO5479599

Drug: RO5479599

Drug: Erlotinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT01482377

2011-002698-53 (EudraCT Number)

BP27771

Details and patient eligibility

About

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.

Enrollment

145 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 (</= 1), except for alopecia and 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)

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

145 participants in 4 patient groups

Part A: RO5479599 Dose Escalation

Experimental group

Description:

Participants will receive a dose of 100 milligrams (mg) RO5479599 followed by dose escalation from Day 1 of Cycle 1. RO5479599 dose will be escalated as monotherapy in approximately 6 cohorts with dose increments between cohorts of up to 100 percent (%) until MTD.

Treatment:

Drug: RO5479599

Part B: RO5479599 Dose Escalation + Cetuximab

Experimental group

Description:

Participants will receive RO5479599 in combination with cetuximab. Escalation of RO5479599 in combination with cetuximab will start in a standard 3+3 design until MTD/OBD is reached. If the initial combination is not tolerated, further cohorts will be dosed with the same dose of cetuximab and lower doses of RO5479599.

Treatment:

Drug: Cetuximab

Drug: RO5479599

Part C: RO5479599 Dose Escalation + Erlotinib

Experimental group

Description:

Participants will receive RO5479599 in combination with erlotinib. Escalation of RO5479599 in combination with erlotinib will start in a standard 3+3 design until MTD/OBD is reached. If the initial combination is not tolerated, further cohorts will be dosed with the same dose of erlotinib and lower doses of RO5479599.

Treatment:

Drug: RO5479599

Drug: Erlotinib

Imaging (IMG) Substudy

Experimental group

Description:

RO5479599 will be administered with zirconium- 89-labeled RO5479599.

Treatment:

Drug: zirconium-89-labeled RO5479599

Drug: RO5479599