A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors
- Registration Number
- NCT02650713
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 228
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab RO6958688 Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. Dose-Escalation (Part IA): RO6958688 + Atezolizumab RO6958688 Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study. Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab Atezolizumab Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. Dose-Escalation (Part IA): RO6958688 + Atezolizumab Atezolizumab Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Dose-Limiting Toxicities (DLTs) Day 1 up to Day 21 Maximum-Tolerated Dose (MTD) of RO6958688 Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation Number of Participants with Adverse Events (AEs) Baseline up to 60 months Recommended Phase II Dose (RP2D) of RO6958688 Day 1 up to 60 months
- Secondary Outcome Measures
Name Time Method PK: AUC of Atezolizumab Baseline up to 60 months PK: Cmax of Atezolizumab Baseline up to 60 months PK: Clearance (CL) of RO6958688 Baseline up to 60 months PK: Vss of Atezolizumab Baseline up to 60 months Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days) Best Overall Response (BOR) Baseline up to 60 months Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
PK: Maximum Serum Concentration (Cmax) of RO6958688 Baseline up to 60 months PK: CL of Atezolizumab Baseline up to 60 months Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST]) Baseline up to 60 months Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST Baseline up to 60 months Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Duration of Response (DOR) as Assessed Using RECIST From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months) Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Overall Survival (OS) From first study treatment to death from any cause (up to 60 months) Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
PK: Volume of Distribution at Steady State (Vss) of RO6958688 Baseline up to 60 months Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688 Baseline up to 60 months Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST Baseline up to 60 months Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Progression-Free Survival (PFS) according to RECIST V1.1 From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months) Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Trial Locations
- Locations (24)
UCLA Cancer Center
🇺🇸Santa Monica, California, United States
Stanford Comprehensive Cancer Center
🇺🇸Stanford, California, United States
Rigshospitalet; Onkologisk Klinik
🇩🇰København Ø, Denmark
University Of Colorado
🇺🇸Aurora, Colorado, United States
Dana Farber Can Ins
🇺🇸Boston, Massachusetts, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
🇺🇸New Haven, Connecticut, United States
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Columbia Univ Med Ctr
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
🇳🇱Amsterdam, Netherlands
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
🇮🇹Siena, Toscana, Italy
IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
🇮🇹Napoli, Campania, Italy
Institut Gustave Roussy
🇫🇷Villejuif, France
Hospital del Mar; Servicio de Oncologia
🇪🇸Barcelona, Spain
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
🇪🇸Madrid, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Sarah Cannon Cancer Center
🇺🇸Germantown, Tennessee, United States