NeoplasmsPhase 1NCT01482377
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
A Phase 1 study testing RO5479599, Cetuximab and Erlotinib in people with Neoplasms, run by Hoffmann-La Roche at 12 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- RO5479599, Cetuximab and Erlotinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 12 sitesin 4 countries
- Study dates
- Dec 2011to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
Spain5 sites
Hospital del Mar; Servicio de Oncologia
Barcelona, Barcelona, 08003
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Barcelona, 08035
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Madrid, Madrid, 28050
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
Seville, Sevilla, 41013
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, Valencia, 46010
Netherlands4 sites
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX
Academ Ziekenhuis Groningen; Medical Oncology
Groningen, 9713 GZ
Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed
Rotterdam, 3075EA
Utrecht University Medical Centre; Dept of Medical Oncology and UPC
Utrecht, 3584 CW
South Korea2 sites
National Cancer Center
Gyeonggi-do, 10408
Asan Medical Center
Seoul, 05505
About this study
Official title: 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
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
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO5479599Drug
RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).
CetuximabDrug
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.
ErlotinibDrug
Erlotinib, at a dose of 150 mg will be administered.
zirconium-89-labeled RO5479599Drug
Single dose of radiolabeled drug will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Part A: RO5479599 Dose Escalation | Experimental | 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. Receives: Drug: RO5479599 |
| Part B: RO5479599 Dose Escalation + Cetuximab | Experimental | 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. Receives: Drug: RO5479599; Drug: Cetuximab |
| Part C: RO5479599 Dose Escalation + Erlotinib | Experimental | 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. Receives: Drug: RO5479599; Drug: Erlotinib |
| Imaging (IMG) Substudy | Experimental | RO5479599 will be administered with zirconium- 89-labeled RO5479599. Receives: Drug: RO5479599; Drug: zirconium-89-labeled RO5479599 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events
Measured: Baseline up to 28 days after last dose (approximately 48 months)
Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of RO5479599
Measured: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Number of Participants With Dose Limiting Toxicities (DLTs)
Measured: 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)
Measured: From baseline to Day 8
Secondary outcomes (48)
Percentage Change From Baseline in Standardized Uptake Value (SUV) of 89ZrRO5479599 at Pharmacodynamic (PD) active dose as Determined by PET Scan
Measured: From baseline to Day 22
Part A: Recommended Phase II Dose (RPTD) of RO5479599 in Monotherapy
Measured: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Part B: Recommended Phase II Dose of RO5479599 in Combination With Cetuximab
Measured: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Part C: Recommended Phase II Dose of RO5479599 in Combination With Erlotinib
Measured: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for two weekly schedule [Q2W] and every ninth week for three weekly schedule [Q3W] up to approximately 48 months)
Percentage of Participants With Disease Control According to RECIST version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Duration of Response According to RECIST version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Progression Free Survival According to RECIST version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Maximum Serum Concentration (Cmax) of RO5479599 for Q2W Schedule
Measured: Pre-infusion (PrI, 0 hours [hr]) & end of infusion (EOI, 1.5 hr) on each 2-week cycle (Cy); 2, 5 hr post-infusion (PoI) on Cy1 Day 1 (D1), Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Cmax of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Trough Serum Concentration (Cmin) for Q2W Schedule
Measured: PreI (0 hr) on D1 of each cycle from Cy2 (up to 48 months overall) (Cycle length = 14 days)
Cmin for Q3W Schedule
Measured: PreI (0 hr) on D1 of each cycle from Cy2 (up to 48 months overall) (Cycle length = 21 days)
Time to Reach Maximum Serum Concentration (Tmax) of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Tmax of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Area Under the Plasma Concentration-Time Curve (AUC) of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
AUC of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Clearance (CL) of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
CL of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Volume of Distribution (Vd) of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Vd of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Accumulation Ratio of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Accumulation Ratio of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Terminal Elimination Half-Life (t1/2) of RO5479599 for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
t1/2 of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Serum Concentration of RO5479599 at Time of Tumor Progression (Cprog) for Q2W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Cprog of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Serum Concentration of RO5479599 at the Time of Tumor Response for Q2W Schedule
Measured: At the time of objective response (up to 48 months)
Serum Concentration of RO5479599 at the Time of Tumor Response for Q3W Schedule
Measured: At the time of objective response (up to 48 months)
Serum Concentration of RO5479599 at the Time of DLT for Q2W Schedule
Measured: At the time of DLT (up to 28 days)
Serum Concentration of RO5479599 at the Time of DLT for Q3W Schedule
Measured: At the time of DLT (up to 28 days)
Serum Concentration of RO5479599 at the Time of Tumor and Skin Biopsy (Cb) for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 and on Cy1 Day 14 (Cycle length = 14 days)
Cb of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 and on Cy1 Day 21 (Cycle length = 21 days)
Serum Concentration of RO5479599 at the Time of PET Scan (Cpet) for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1, Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Cpet of RO5479599 for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1, Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Serum Concentration of RO5479599 at Time of Infusion-Related Reactions (IRRs) for Q2W Schedule
Measured: At the time of IRR (up to 48 months)
Serum Concentration of RO5479599 at Time of IRRs for Q3W Schedule
Measured: At the time of IRR (up to 48 months)
Change from Baseline in T Lymphocytes Cell Count for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in T lymphocytes Cell Count for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in Natural Killer Cell Count for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in Natural Killer Cell Count for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in Macrophages Cell Count for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in Macrophages Cell Count for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in Cytokines Level for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in Cytokines Level for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in HER3 Expression for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in HER3 Expression for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in Phosphorylated HER3 Expression for Q2W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in Phosphorylated HER3 Expression for Q3W Schedule
Measured: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2011 (estimated)
- Study startDec 2011
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01482377
- Sponsor's protocol ID
- BP27771
- Other IDs
- 2011-002698-53
- Status last verified
- Jan 2017
- First submitted
- 28 Nov 2011
- Last updated
- 27 Jan 2017
- Results posted
- No
Publications
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.
PubMed 30268483
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01482377
- Acronym / sponsor ID
- BP27771
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 30 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A: RO5479599 Dose Escalation | Experimental | Drug: RO5479599Participants 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. |
| Part B: RO5479599 Dose Escalation + Cetuximab | Experimental | Drug: RO5479599, Drug: CetuximabParticipants 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. |
| Part C: RO5479599 Dose Escalation + Erlotinib | Experimental | Drug: RO5479599, Drug: ErlotinibParticipants 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. |
| Imaging (IMG) Substudy | Experimental | Drug: RO5479599, Drug: zirconium-89-labeled RO5479599RO5479599 will be administered with zirconium- 89-labeled RO5479599. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO5479599RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part). | Drug | Imaging (IMG) Substudy, Part A: RO5479599 Dose Escalation, Part B: RO5479599 Dose Escalation + Cetuximab, Part C: RO5479599 Dose Escalation + Erlotinib |
| CetuximabCetuximab 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. | Drug | Part B: RO5479599 Dose Escalation + Cetuximab |
| ErlotinibErlotinib, at a dose of 150 mg will be administered. | Drug | Part C: RO5479599 Dose Escalation + Erlotinib |
| zirconium-89-labeled RO5479599Single dose of radiolabeled drug will be administered. | Drug | Imaging (IMG) Substudy |
Primary outcome
Percentage of Participants With Adverse Events
Time frame: Baseline up to 28 days after last dose (approximately 48 months)
Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of RO5479599
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: 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)
Time frame: From baseline to Day 8
48 secondary outcomes
Percentage Change From Baseline in Standardized Uptake Value (SUV) of 89ZrRO5479599 at Pharmacodynamic (PD) active dose as Determined by PET Scan
Time frame: From baseline to Day 22
Part A: Recommended Phase II Dose (RPTD) of RO5479599 in Monotherapy
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Part B: Recommended Phase II Dose of RO5479599 in Combination With Cetuximab
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Part C: Recommended Phase II Dose of RO5479599 in Combination With Erlotinib
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for two weekly schedule [Q2W] and every ninth week for three weekly schedule [Q3W] up to approximately 48 months)
Percentage of Participants With Disease Control According to RECIST version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Duration of Response According to RECIST version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Progression Free Survival According to RECIST version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for Q2W and every ninth week for Q3W up to approximately 48 months)
Maximum Serum Concentration (Cmax) of RO5479599 for Q2W Schedule
Time frame: Pre-infusion (PrI, 0 hours [hr]) & end of infusion (EOI, 1.5 hr) on each 2-week cycle (Cy); 2, 5 hr post-infusion (PoI) on Cy1 Day 1 (D1), Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Cmax of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Trough Serum Concentration (Cmin) for Q2W Schedule
Time frame: PreI (0 hr) on D1 of each cycle from Cy2 (up to 48 months overall) (Cycle length = 14 days)
Cmin for Q3W Schedule
Time frame: PreI (0 hr) on D1 of each cycle from Cy2 (up to 48 months overall) (Cycle length = 21 days)
Time to Reach Maximum Serum Concentration (Tmax) of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Tmax of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Area Under the Plasma Concentration-Time Curve (AUC) of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
AUC of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Clearance (CL) of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
CL of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Volume of Distribution (Vd) of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Vd of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Accumulation Ratio of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Accumulation Ratio of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Terminal Elimination Half-Life (t1/2) of RO5479599 for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
t1/2 of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Serum Concentration of RO5479599 at Time of Tumor Progression (Cprog) for Q2W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 2-week Cy; 2, 5 hr PoI on Cy1 D1, Cy1 Days 2, 3, 5, 8, 12; 2 hr PoI on Cy4D1; Cy4 Days 2, 3, 5, 8; Cy8 Days 2, 5, 8 (up to 48 months overall)
Cprog of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) & EOI (1.5 hr) on each 3-week Cy; 3 hr PoI on Cy1 D1, Cy1 Days 2, 4, 8, 12, 14, 19, 21; 3 hr PoI on Cy4 D1, Cy8 D1; Days 2, 4, 8, 12, 14, 19, 21 on Cy4 and Cy8 (up to 48 months overall)
Serum Concentration of RO5479599 at the Time of Tumor Response for Q2W Schedule
Time frame: At the time of objective response (up to 48 months)
Serum Concentration of RO5479599 at the Time of Tumor Response for Q3W Schedule
Time frame: At the time of objective response (up to 48 months)
Serum Concentration of RO5479599 at the Time of DLT for Q2W Schedule
Time frame: At the time of DLT (up to 28 days)
Serum Concentration of RO5479599 at the Time of DLT for Q3W Schedule
Time frame: At the time of DLT (up to 28 days)
Serum Concentration of RO5479599 at the Time of Tumor and Skin Biopsy (Cb) for Q2W Schedule
Time frame: PrI (0 hr) on Cy1D1 and on Cy1 Day 14 (Cycle length = 14 days)
Cb of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) on Cy1D1 and on Cy1 Day 21 (Cycle length = 21 days)
Serum Concentration of RO5479599 at the Time of PET Scan (Cpet) for Q2W Schedule
Time frame: PrI (0 hr) on Cy1D1, Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Cpet of RO5479599 for Q3W Schedule
Time frame: PrI (0 hr) on Cy1D1, Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Serum Concentration of RO5479599 at Time of Infusion-Related Reactions (IRRs) for Q2W Schedule
Time frame: At the time of IRR (up to 48 months)
Serum Concentration of RO5479599 at Time of IRRs for Q3W Schedule
Time frame: At the time of IRR (up to 48 months)
Change from Baseline in T Lymphocytes Cell Count for Q2W Schedule
Time frame: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in T lymphocytes Cell Count for Q3W Schedule
Time frame: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Change from Baseline in Natural Killer Cell Count for Q2W Schedule
Time frame: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 14, and Cy4 Day 14 (Cycle length = 14 days)
Change from Baseline in Natural Killer Cell Count for Q3W Schedule
Time frame: PrI (0 hr) on Cy1D1 (Baseline), Cy1 Day 21, and Cy3 Day 21 (Cycle length = 21 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2017.
- Derived from this study: PubMed 30268483Kim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO5479599, Cetuximab and Erlotinib in people with Neoplasms, run by Hoffmann-La Roche at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain, Netherlands, South Korea, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (time frame: Baseline up to 28 days after last dose (approximately 48 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01482377, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2017.