gevorderde en/of gemetastaseerde solide tumoren cancer solid tumors
Conditions
Interventions
Eligible patients will be treated with RO5479599 according to the schedulde of
assessment (tabel 5, page 60/61 and table 6 page 64 of the protocol).
Substudy BP27771/IMG
Eligible patients will be tr
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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;• Life expectancy of >= 12 weeks. ;• 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 A extension cohort: : In addition to the above inclusion criteria, patients will be eligible if they have metastatic and/or locally advanced malignant HER3-expressing solid tumors of epithelial cell origin;• 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 (CRC must be EGFR pos. and KRAS wt).;• Part C extension cohort: In addition to the above inclusion criteria, patients will be eligible if they have metastatic and/or locally advanced squamous non-small cell lung cancer or non-squamous carcinomas with documented NRG1 somatic gene fusion
Exclusion criteria
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;• HIV infection;• Major surgery or significant traumatic injury < 28 days prior to the 1st RO5479599 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment.;• 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);• Baseline QTc interval of > 470 ms, patients with baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia > 100 beats per minute.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A To describe the safety profile (including the maximum tolerated dose [MTD] and/or the optimal biological dose [OBD]) and pharmacokinetics (PK) of escalating doses of RO5479599 monotherapy in patients with metastatic and/or locally advanced malignant HER3-expressing solid tumors. Part B and C To describe the safety profile (including the maximum tolerated dose [MTD] and/or optimal biological dose [OBD]) and pharmacokinetics (PK) of escalating doses of RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C) in patients with metastatic and/or locally advanced malignant HER3-expressing solid tumors. Substudy BP27771/IMG The rationale of this study is to evaluate the in vivo biodistribution and organ pharmacokinetics (PK) of zirconium-89-labeled RO5479599 (89Zr-RO5479599) in patients with metastatic and/or locally advanced HER3-expressing tumor of epithelial origin. Inclusion criteria: Same as main study Exclusion criteria: (All criteria set out in the main study is applicable with the below additions) • Known or clinically suspected central nervous system (CNS) primary tumors. 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. Patients revealing newly diagnosed asymptomatic brain metastases by PET imaging during the study will be allowed to remain on the study according to the investigator*s judgment. • Known hypersensitivity to any of the components of RO5479599 and/ or 89Zr-RO5479599. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A dose escalation phase To determine the recommended phase II dose(s) (RPTD) and schedule(s) for RO5479599 monotherapy. To describe the preliminary anti-tumor activity of RO5479599 monotherapy by assessing objective response rate, disease control rate and duration of response. Part A extension phase To determine the recommended phase II dose(s) (RPTD) and schedule(s) for RO5479599 monotherapy. To investigate the anti-tumor activity of RO5479599 monotherapy through disease control rate, objective response rate, duration of response and progression-free survival (PFS). To describe the PK profile of RO5479599 monotherapy. To describe the pharmacodynamic effects of RO5479599 monotherapy. Part B and C dose escalation phase To determine the recommended phase II dose(s) (RPTD) and schedule(s) for RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C). To describe the anti-tumor activity of RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C) by assessing objective response rate, disease control rate and duration of response. Part B and C extension phase To determine the recommended phase II dose(s) (RPTD) and schedule(s) for RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C). To investigate the anti-tumor activity of RO5479599 monotherapy through disease control rate, objective response rate, duration of response and progression-free survival (PFS). To describe the PK profile of RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C). To describe the pharmacodynamic effects of RO5479599 in combination with cetuximab (Part B) and in combination with erlotinib (Part C). Substudy BP27771/IMG Secundairy Objectives • To explore the target saturation by RO5479599, defined as decrease in tissue uptake of radioactivity concentration, and correlate it with PK/pharmacodynamics (PD) effects. | — |
Countries
Netherlands
Outcome results
None listed