A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors

Neoplasms Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02760797
• Other study ID #: BP29427
• Secondary ID: 2015-004348-21
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2016
• Est. completion date: April 6, 2018

Study information

• Verified date: May 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: April 6, 2018
• Est. primary completion date: April 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Emactuzumab
Emactuzumab will be administered IV every 3 weeks (every cycle) during Part I and every 3 or 6 weeks (every cycle or every other cycle) during Part II.
• RO7009789
RO7009789 will be administered IV every 3 weeks (every cycle).

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Institut Gustave Roussy; Sitep	VILLEJUIF Cedex
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University Pennsylvania Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Dose-Limiting Toxicities (DLTs)		Up to 6 weeks from Day (D) 1 of Cycle (C) 1 (cycle = 3 weeks)
Secondary	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)
Secondary	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)
Secondary	Serum Maximum Concentration (Cmax) of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	Serum Trough Concentration (Ctrough) of Emactuzumab		PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years)
Secondary	Area Under the Concentration-Time Curve (AUC) of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	Total Clearance (CL) of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	Volume of Distribution at Steady State (Vss) of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	Accumulation Ratio of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	Terminal Elimination Half-Life (T1/2) of Emactuzumab	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)	PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
Secondary	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)
Secondary	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)
Secondary	Concentration of Emactuzumab at Time of Infusion-Related Reaction (IRR) or Hypersensitivity Reaction		At time of IRR or hypersensitivity reaction (up to 2 years)
Secondary	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)
Secondary	Ctrough of RO7009789		PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Levels of Functional Tumor-Infiltrating Lymphocytes		Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Duration of Response (DOR) as Assessed by RECIST v1.1		From OR until PD; assessed every 6 weeks (up to 2 years overall)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Progressive-Free Survival (PFS) as Assessed by Modified RECIST		From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall)
Secondary	Duration of Response (DOR) as Assessed by Modified RECIST		From OR until PD; assessed every 6 weeks (up to 2 years overall)
Secondary	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)