A Study to Evaluate Safety, Pharmacokinetics and Anti-Tumor Activity of RO7300490, as Single Agent or in Combination With Atezolizumab in Participants With Advanced Solid Tumors
- Registration Number
- NCT04857138
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: \[Part 1\] Dose-Escalation of RO7300490 as a single agent; \[Part 2\] Dose-Escalation of RO7300490 in combination with atezolizumab and \[Part 3\] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria
- Life expectancy of >= 12 weeks.
- Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy.
- Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Agreement to provide protocol-specific biopsy material.
- Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<1.
- Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function.
- For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs.
- For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.
Exclusion Criteria
- Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met.
- Active second invasive malignancy within two years prior to screening.
- Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start.
- Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
- Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
- Active or history of autoimmune disease.
- Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation.
- Pregnancy, lactation or breastfeeding.
- Dementia or altered mental status that would prohibit informed consent.
- Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment.
- Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy) RO7300490 Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. Part 1: Dose Escalation (RO7300490 Monotherapy) RO7300490 Participants will receive escalating doses of RO7300490 intravenously (IV) as a single agent for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy) Atezolizumab Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. Part 3: Dose Expansion (Disease-specific Expansion(s)) Atezolizumab Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. Part 3: Dose Expansion (Disease-specific Expansion(s)) RO7300490 Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) (Part 3) Up to 48 months Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2) Up to 36 months Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2) Up to 36 months
- Secondary Outcome Measures
Name Time Method Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3) Up to 48 months Clearance (CL) of RO7300490 (Parts 1, 2 and 3) Up to 48 months Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3) Up to 48 months Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3) Up to 48 months Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3) Up to 48 months Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3) Up to 48 months Objective Response Rate (ORR) (Parts 1 and 2) Up to 48 months Disease Control Rate (DCR) (Parts 1, 2 and 3) Up to 48 months Duration of Response (DOR) (Parts 1, 2 and 3) Up to 48 months Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3) Up to 48 months Percentage of Participants With Adverse Events (AEs) (Part 3) Up to 48 months
Trial Locations
- Locations (11)
Gustave Roussy
🇫🇷Villejuif, France
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Western General Hospital; Edinburgh Cancer Center
🇬🇧Edinburgh, United Kingdom
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Guys and St Thomas Hospital; OHCT Clinical Trials
🇬🇧London, United Kingdom
Clinica Universidad de Navarra Madrid; Servicio de OncologÃa
🇪🇸Madrid, Spain
Christie Hospital NHS Trust; Experimental Cancer Medicine Team
🇬🇧Manchester, United Kingdom
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Rigshospitalet; Fase 1 Enhed - Onkologi
🇩🇰København Ø, Denmark
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain