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

Hoffmann-La Roche6 sites in 3 countries38 target enrollmentMay 9, 2016

ConditionsNeoplasms

InterventionsEmactuzumab RO7009789

DrugsEmactuzumab RO7009789

Overview

Phase: Phase 1
Intervention: Emactuzumab
Conditions: Neoplasms
Sponsor: Hoffmann-La Roche
Enrollment: 38
Locations: 6
Primary Endpoint: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

May 9, 2016

End Date

April 6, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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

Arms & Interventions

Part I (Dose-Finding Stage)

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.

Intervention: Emactuzumab

Part I (Dose-Finding Stage)

Intervention: RO7009789

Part II (Dose Expansion Stage)

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.

Intervention: Emactuzumab

Part II (Dose Expansion Stage)

Intervention: RO7009789

Outcomes

Primary Outcomes

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)

Secondary Outcomes

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)
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)
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)
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)
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)
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)
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))