A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors
- Registration Number
- NCT02760797
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is an open-label, multicenter study designed to assess the safety, pharmacokinetics, pharmacodynamics, and therapeutic activity of emactuzumab and RO7009789 administered in combination in participants with locally advanced or metastatic solid tumors that are not amenable to standard treatment. This study will be conducted in two parts: a dose-finding stage (Part I) and an expansion stage (Part II).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Inclusion Criteria
- Eastern Cooperative Oncology Group performance status 0 or 1
- Histologically confirmed diagnosis of locally advanced, recurrent, and/or metastatic triple-negative breast cancer, ovarian cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, or mesothelioma
- Radiologically measurable and clinically evaluable disease as per RECIST v1.1
- Life expectancy of greater than or equal to (>/=) 16 weeks
- Ability to comply with the collection of tumor biopsies; tumors accessible for biopsy
- Adequate bone marrow, liver, cardiac, and renal function
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Exclusion Criteria
- Allergy or hypersensitivity to components of either study drug formulation
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments. Participants with radiographically stable, asymptomatic, previously irradiated lesions are eligible provided participant is >/=4 weeks beyond completion of cranial irradiation and >/=3 weeks off of corticosteroid therapy
- Participants with leptomeningeal disease; metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeters (mm) of the optic apparatus (optic nerves and chiasm)
- History of human immunodeficiency virus (HIV)
- Participants with active hepatitis B, active hepatitis C, or active tuberculosis
- Pregnant or lactating women
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part I (Dose-Finding Stage) RO7009789 Emactuzumab and RO7009789 will be administered intravenously (IV) at a starting dose of 500 milligrams (mg) for emactuzumab and 2 mg for RO7009789. Treatment will continue as long as there is clinical benefit until unacceptable toxicity, symptomatic deterioration, or withdrawal of consent. Part II (Dose Expansion Stage) RO7009789 Emactuzumab and RO7009789 will be administered IV at the maximum tolerated dose defined in Part I of the study. Treatment will continue as long as there is clinical benefit until unacceptable toxicity, symptomatic deterioration, or withdrawal of consent. Part II (Dose Expansion Stage) Emactuzumab Emactuzumab and RO7009789 will be administered IV at the maximum tolerated dose defined in Part I of the study. Treatment will continue as long as there is clinical benefit until unacceptable toxicity, symptomatic deterioration, or withdrawal of consent. Part I (Dose-Finding Stage) Emactuzumab Emactuzumab and RO7009789 will be administered intravenously (IV) at a starting dose of 500 milligrams (mg) for emactuzumab and 2 mg for RO7009789. Treatment will continue as long as there is clinical benefit until unacceptable toxicity, symptomatic deterioration, or withdrawal of consent.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Dose-Limiting Toxicities (DLTs) Up to 6 weeks from Day (D) 1 of Cycle (C) 1 (cycle = 3 weeks)
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emactuzumab Predose (PrD) (0 hours [H]) on D1 each cycle (cycle = 3 weeks) until progressive disease (PD) (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall) Percentage of Participants with ADAs to RO7009789 PrD (0 H) on D1 each cycle (cycle = 3 weeks) until PD (up to 2 years); at 120 days after last dose (up to 2 years overall) Serum Maximum Concentration (Cmax) of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), end of infusion (EOI) (infusion = 90 minutes \[min\]), postdose \[5 H\] D1 of C1/C4 (cycle = 3 weeks); on D2, 5, 8, 12, 15, 19 of C1/C4; on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Serum Trough Concentration (Ctrough) of Emactuzumab PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years) Area Under the Concentration-Time Curve (AUC) of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), EOI (infusion = 90 min), postdose \[5 H\] D1 of C1/C4; on D2, 5, 8, 12, 15, 19 of C1/C4 (cycle = 3 weeks); on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Total Clearance (CL) of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), EOI (infusion = 90 min), postdose \[5 H\] D1 of C1/C4; on D2, 5, 8, 12, 15, 19 of C1/C4 (cycle = 3 weeks); on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Volume of Distribution at Steady State (Vss) of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), EOI (infusion = 90 min), postdose \[5 H\] D1 of C1/C4; on D2, 5, 8, 12, 15, 19 of C1/C4 (cycle = 3 weeks); on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Accumulation Ratio of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), EOI (infusion = 90 min), postdose \[5 H\] D1 of C1/C4; on D2, 5, 8, 12, 15, 19 of C1/C4 (cycle = 3 weeks); on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Terminal Elimination Half-Life (T1/2) of Emactuzumab PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details PrD (0 H), EOI (infusion = 90 min), postdose \[5 H\] D1 of C1/C4; on D2, 5, 8, 12, 15, 19 of C1/C4 (cycle = 3 weeks); on D5, 8, 12, 17 of C2; on D2, 8, 15 of C3; PrD (0 H), EOI on D1 of C2, 3, 5 onwards until/at PD (up to 2 years); at 28, 44, 120 days after last dose (up to 2 years overall)
Concentration at Time of Tumor Progression (Cprog) of Emactuzumab According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 At time of PD (up to 2 years) Concentration of Emactuzumab at Time of Tumor Response (Complete or Partial Response) According to RECIST v1.1 At time of tumor response (up to 2 years) Concentration of Emactuzumab at Time of Infusion-Related Reaction (IRR) or Hypersensitivity Reaction At time of IRR or hypersensitivity reaction (up to 2 years) Cmax of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) Ctrough of RO7009789 PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years) AUC of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) CL of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) Vss of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) Accumulation Ratio of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) T1/2 of RO7009789 PrD (0 H), 15 min during infusion, EOI (infusion = 30 min), postdose (2, 4, 6 H) on D1 of C1 (cycle = 3 weeks); on D2, 3, 8 of C1; PrD (0 H), EOI on D1 of C2 onwards until/at PD (up to 2 years); at 120 days after last dose (up to 2 years overall) Total Tumor-Associated Macrophages (TAMs) in Paired-Tumor Biopsies Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) Total Dermal Macrophages in Paired-Skin Biopsies Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) Levels of Functional Tumor-Infiltrating Lymphocytes Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) Total Dendritic Cell Count in Peripheral Blood Baseline; on D2, 5, 8, 15 of C1/C3 (cycle = 3 weeks); PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Circulating Cluster of Differentiation (CD) 4 T Cell Count in Peripheral Blood Baseline; on D2, 5, 8, 15 of C1/C3 (cycle = 3 weeks); PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Circulating Colony-Stimulating Factor (CSF)-1 Serum Levels Baseline; on D2, 5, 8, 15 of C1 (cycle = 3 weeks); on D2, 5, 15 of C3; PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Total Monocyte Count in Peripheral Blood Baseline; on D2, 5, 8, 15 of C1/C3 (cycle = 3 weeks); PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Circulating CD8 T Cell Count in Peripheral Blood Baseline; on D2, 5, 8, 15 of C1/C3 (cycle = 3 weeks); PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Circulating B Cell Count in Peripheral Blood Baseline; on D2, 5, 8, 15 of C1/C3 (cycle = 3 weeks); PrD (+/- 1 day) on D1 of each cycle until/at PD (up to 2 years); at 44, 120 days after last dose (up to 2 years overall) Duration of Response (DOR) as Assessed by RECIST v1.1 From OR until PD; assessed every 6 weeks (up to 2 years overall) Percentage of Participants with Clinical Benefit as Assessed by RECIST v1.1 Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Percentage of Participants by Best Overall Response as Assessed by Modified RECIST Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Percentage of Participants with Overall Response as Assessed by Modified RECIST Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Progressive-Free Survival (PFS) as Assessed by Modified RECIST From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall) Duration of Response (DOR) as Assessed by Modified RECIST From OR until PD; assessed every 6 weeks (up to 2 years overall) Percentage of Participants with Clinical Benefit as Assessed by Modified RECIST Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Metabolic Response of Target Lesions Assessed as the Change in Maximum Standardized Uptake Value (SUVmax) on [18F]-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Baseline; on D15 of C1; PrD (+/- 4 days) on D1 of C3 (cycle = 3 weeks) Percentage of Participants by Best Overall Response as Assessed by RECIST v1.1 Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Percentage of Participants with Overall Response as Assessed by RECIST v1.1 Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) Progressive-Free Survival (PFS) as Assessed by RECIST v1.1 From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall)
Trial Locations
- Locations (6)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Institut Gustave Roussy; Sitep
🇫🇷VILLEJUIF Cedex, France
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
Institut Claudius Regaud; Departement Oncologie Medicale
🇫🇷Toulouse, France
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium