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

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

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).

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Emactuzumab; Drug: RO7009789

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
• France
  • Lyon, France, 69373
    • Centre Leon Berard; Departement Oncologie Medicale
  • Toulouse, France, 31059
    • Institut Claudius Regaud; Departement Oncologie Medicale
  • VILLEJUIF Cedex, France, 94805
    • Institut Gustave Roussy; Sitep
• United States
  • New York
    • New York, New York, United States
      • Memorial Sloan-Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: RO5509554; Drug: RO7009789; RO7009789 will be administered IV every 3 weeks (every cycle).
Experimental: 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.	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.; Other Names: RO5509554; Drug: RO7009789; RO7009789 will be administered IV every 3 weeks (every cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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), 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
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), 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
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
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
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
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
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)
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)
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 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)
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)
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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Machiels JP, Gomez-Roca C, Michot JM, Zamarin D, Mitchell T, Catala G, Eberst L, Jacob W, Jegg AM, Cannarile MA, Watson C, Babitzki G, Korski K, Klaman I, Teixeira P, Hoves S, Ries C, Meneses-Lorente G, Michielin F, Christen R, Ruttinger D, Weisser M, Delord JP, Cassier P. Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients. J Immunother Cancer. 2020 Oct;8(2):e001153. doi: 10.1136/jitc-2020-001153.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2016
• Primary Completion (Actual): April 6, 2018
• Study Completion (Actual): April 6, 2018

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimate): May 4, 2016

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: BP29427; 2015-004348-21 (EudraCT Number)