This is a first-in-human, open-label, multi-center, Phase 1 study of RO6927005. The study will establish the safety and tolerability profile of RO6927005 and will be conducted in two parts. In Part A, the first dose escalations will be carried out using cohorts of 1 patient. Single patient cohorts will be used to investigate increasing doses until a first dose-limiting toxicity (DLT) is reached or until grade-2 related toxicity (except infusion-related reactions), whichever comes first. At least 3 patients will be enrolled in each cohort thereafter, which, if required, can be expanded with additional patients. Part B of the study will consist of a multiple ascending dose phase (multiple patients cohorts - \>/= 3 patients) followed by an extension phase of RO6927005 given in combination with gemcitabine/nab-paclitaxel. Preliminary clinical activity will be explored throughout the study. Patients will be treated until disease progression and/or lack of clinical benefit, unacceptable toxicities, withdrawal from treatment for other reasons, death, pregnancy or termination of the study by the Sponsor, whichever comes first.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
RO6927005 administered intravenously on Days 1, 3, and 5 of each 21-day treatment cycle (QOD x 3).
RO6927005 administered intravenously on Days 1, 3, and 5 of each 28-day treatment cycle (QOD x 3).
gemcitabine administered according to local label on Days 1, 8, and 15 of each 28-day cycle.
nab-paclitaxel administered according to the local label on Days 1, 8, and 15 of each 28-day cycle.
Unnamed facility
Bethesda, Maryland, United States
Unnamed facility
Toronto, Ontario, Canada
Unnamed facility
København Ø, Denmark
Unnamed facility
Bordeaux, France
Unnamed facility
Toulouse, France
Unnamed facility
Villejuif, France
Safety: incidence of dose-limiting toxicities, adverse events, laboratory abnormalities; incidence of anti-drug antibodies, abnormal findings on physical examination, infusion-related reactions (composite outcome measure)
Time frame: Until disease progression, unacceptable toxicities, withdrawal for other reasons, death, or termination of the study by the Sponsor, whichever comes first, up to 2 years 8 months
Pharmacokinetic profile of RO6927005 monotherapy based on free and total plasma RO6927005 concentrations over time (area under the curve)
Time frame: Up to 2 years 8 months
Pharmacokinetic profile of RO6927005 in combination with gemcitabine/nab-paclitaxel, based on free and total plasma RO6927005 concentrations over time (area under the curve)
Time frame: Up to 2 years 8 months
Efficacy: objective response rate, disease control rate, duration of response, progression-free survival, overall survival (composite outcome measure)
Time frame: Up to 2 years 8 months
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