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

NCT ID: NCT01482377

Last Updated: 2017-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2016-02-29

Brief 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.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: RO5479599 Dose Escalation

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.

Group Type: EXPERIMENTAL

RO5479599

Intervention Type: DRUG

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

Part B: RO5479599 Dose Escalation + Cetuximab

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.

Group Type: EXPERIMENTAL

RO5479599

Intervention Type: DRUG

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

Cetuximab

Intervention Type: DRUG

Cetuximab will be administered via intravenous (IV) infusion at a starting dose of 400 mg/m\^2 for the first infusion, followed by doses of 250 mg/m\^2 for subsequent infusions.

Part C: RO5479599 Dose Escalation + Erlotinib

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.

Group Type: EXPERIMENTAL

RO5479599

Intervention Type: DRUG

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

Erlotinib

Intervention Type: DRUG

Erlotinib, at a dose of 150 mg will be administered.

Imaging (IMG) Substudy

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

Group Type: EXPERIMENTAL

RO5479599

Intervention Type: DRUG

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

zirconium-89-labeled RO5479599

Intervention Type: DRUG

Single dose of radiolabeled drug will be administered.

Interventions

RO5479599

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

Intervention Type: DRUG

Cetuximab

Cetuximab will be administered via intravenous (IV) infusion at a starting dose of 400 mg/m\^2 for the first infusion, followed by doses of 250 mg/m\^2 for subsequent infusions.

Intervention Type: DRUG

Erlotinib

Erlotinib, at a dose of 150 mg will be administered.

Intervention Type: DRUG

zirconium-89-labeled RO5479599

Single dose of radiolabeled drug will be administered.

Intervention Type: DRUG

Eligibility 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 (</= 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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Rigshospitalet, Onkologisk Klinik

København Ø, , Denmark

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Academ Ziekenhuis Groningen; Medical Oncology

Groningen, , Netherlands

Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed

Rotterdam, , Netherlands

Utrecht University Medical Centre; Dept of Medical Oncology and UPC

Utrecht, , Netherlands

National Cancer Center

Gyeonggi-do, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital del Mar; Servicio de Oncologia

Barcelona, Barcelona, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Barcelona, Spain

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, Madrid, Spain

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, Sevilla, Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Valencia, Spain

Countries

Denmark; Netherlands; South Korea; Spain

References

Kim HS, Han JY, Shin DH, Lim KY, Lee GK, Kim JY, Jacob W, Ceppi M, Weisser M, James I. EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion. Lung Cancer. 2018 Oct;124:71-75. doi: 10.1016/j.lungcan.2018.07.026. Epub 2018 Jul 20.

Reference Type: DERIVED

PMID: 30268483 (View on PubMed)

Other Identifiers

2011-002698-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP27771

Identifier Type: -

Identifier Source: org_study_id