This is a Phase I, open-label, multicenter study designed to assess the safety and tolerability of RO7051790 in participants with relapsed ED SCLC. This dose escalation and expansion study plans to determine the maximum tolerated dose and/or optimal biological dose as a recommended Phase 2 dose for RO7051790, based on the safety, tolerability, pharmacokinetic and pharmacodynamic profiles observed after oral administration of RO7051790.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
RO7051790 will be given orally. Treatment will be continued until disease progression/treatment failure, unacceptable toxicity, or study discontinuation.
University of Alabama at Birmingham
Birmingham, Alabama, United States
The Ottawa Hospital Cancer Centre; Oncology
Ottawa, Ontario, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada
Rigshospitalet; Onkologisk Klinik
Percentage of Participants with Adverse Events
Time frame: Baseline up to approximately 18 weeks
Number of Participants with Dose-Limited Toxicities (DLTs)
DLTs were to be assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. DLTs were at least possibly related to RO7051790 and had to meet any one of the following criteria: Grade≥4 neutropenia lasting \>7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade≥4 anemia; Febrile neutropenia; Grade≥3 elevation in serum hepatic transaminase lasting \>7 days; Grade≥3 elevation of serum bilirubin; and Grade≥3 non-hematologic, non-hepatic adverse event (with few exceptions).
Time frame: First treatment cycle (21 days)
Percentage of Participants with Best Confirmed Overall Response
Best Confirmed Overall Response was evaluated according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Complete Response (CR) included the disappearance of all target lesions; Partial Response (PR) was at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD) was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (Assessed every 6 weeks up to approximately 18 weeks)
Percentage of Participants with Objective Response According to RECIST
Objective response was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions.
Time frame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
København Ø, Denmark
Institut Gustave Roussy
Villejuif, France
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, Spain
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Madrid, Spain
Duration of Response According to RECIST v1.1
Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier.
Time frame: Time from first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
Progression-Free Survival (PFS) According to RECIST v1.1
Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using RECIST or death from any cause, whichever occurred first.
Time frame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
Overall Survival (OS)
Time frame: Time from first study treatment to death from any cause (up to approximately 12 months)
Maximum Observed Plasma Concentration (Cmax) of RO7051790
Time frame: Predose (0 hours [hrs]) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1,2,4,6,8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8,12,15,19
Minimum Observed Plasma Trough Concentration (Cmin) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Plasma Decay Half-Life (t1/2) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Apparent Oral Clearance (CL/F) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Apparent Volume of Distribution (Vz/F) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Accumulation Ratio (RA) of RO7051790
Time frame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19