Description:
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).
Title
- Brief Title: A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors
- Official Title: An Open-Label, Multicenter, Dose-Escalation Phase Ib Study With Expansion Phase to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Therapeutic Activity of Emactuzumab and RO7009789 Administered in Combination in Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
BP29427
- SECONDARY ID:
2015-004348-21
- NCT ID:
NCT02760797
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Emactuzumab | RO5509554 | Part I (Dose-Finding Stage) |
| RO7009789 | | Part I (Dose-Finding Stage) |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part I (Dose-Finding Stage) | Experimental | 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) | Experimental | 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. | |
Eligibility Criteria
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
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants with Dose-Limiting Toxicities (DLTs) |
| Time Frame: | Up to 6 weeks from Day (D) 1 of Cycle (C) 1 (cycle = 3 weeks) |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emactuzumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants with ADAs to RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Maximum Concentration (Cmax) of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Serum Trough Concentration (Ctrough) of Emactuzumab |
| Time Frame: | PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Area Under the Concentration-Time Curve (AUC) of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Total Clearance (CL) of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Volume of Distribution at Steady State (Vss) of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Accumulation Ratio of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Terminal Elimination Half-Life (T1/2) of Emactuzumab |
| Time Frame: | PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Concentration at Time of Tumor Progression (Cprog) of Emactuzumab According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 |
| Time Frame: | At time of PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Concentration of Emactuzumab at Time of Tumor Response (Complete or Partial Response) According to RECIST v1.1 |
| Time Frame: | At time of tumor response (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Concentration of Emactuzumab at Time of Infusion-Related Reaction (IRR) or Hypersensitivity Reaction |
| Time Frame: | At time of IRR or hypersensitivity reaction (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Cmax of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Ctrough of RO7009789 |
| Time Frame: | PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | AUC of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | CL of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Vss of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Accumulation Ratio of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | T1/2 of RO7009789 |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Total Tumor-Associated Macrophages (TAMs) in Paired-Tumor Biopsies |
| Time Frame: | Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Total Dermal Macrophages in Paired-Skin Biopsies |
| Time Frame: | Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Levels of Functional Tumor-Infiltrating Lymphocytes |
| Time Frame: | Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Circulating Colony-Stimulating Factor (CSF)-1 Serum Levels |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Total Monocyte Count in Peripheral Blood |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Total Dendritic Cell Count in Peripheral Blood |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Circulating Cluster of Differentiation (CD) 4 T Cell Count in Peripheral Blood |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Circulating CD8 T Cell Count in Peripheral Blood |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Circulating B Cell Count in Peripheral Blood |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Metabolic Response of Target Lesions Assessed as the Change in Maximum Standardized Uptake Value (SUVmax) on [18F]-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) |
| Time Frame: | Baseline; on D15 of C1; PrD (+/- 4 days) on D1 of C3 (cycle = 3 weeks) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants by Best Overall Response as Assessed by RECIST v1.1 |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants with Overall Response as Assessed by RECIST v1.1 |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Progressive-Free Survival (PFS) as Assessed by RECIST v1.1 |
| Time Frame: | From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response (DOR) as Assessed by RECIST v1.1 |
| Time Frame: | From OR until PD; assessed every 6 weeks (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants with Clinical Benefit as Assessed by RECIST v1.1 |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants by Best Overall Response as Assessed by Modified RECIST |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants with Overall Response as Assessed by Modified RECIST |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Progressive-Free Survival (PFS) as Assessed by Modified RECIST |
| Time Frame: | From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response (DOR) as Assessed by Modified RECIST |
| Time Frame: | From OR until PD; assessed every 6 weeks (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants with Clinical Benefit as Assessed by Modified RECIST |
| Time Frame: | Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
May 22, 2018
