Clinical trial NCT02760797: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-05-04
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 6 weeks from Day (D) 1 of Cycle (C) 1 (cycle = 3 weeks)
Secondary outcomes:
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Emactuzumab
timeFrame: 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)
measure: Percentage of Participants with ADAs to RO7009789
timeFrame: 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)
measure: Serum Maximum Concentration (Cmax) of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Serum Trough Concentration (Ctrough) of Emactuzumab
timeFrame: PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years)
measure: Area Under the Concentration-Time Curve (AUC) of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Total Clearance (CL) of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Volume of Distribution at Steady State (Vss) of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Accumulation Ratio of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Terminal Elimination Half-Life (T1/2) of Emactuzumab
timeFrame: PrD (0 H) D1 of C1 up to 120 days after last dose (up to 2 years overall); see Outcome Measure Description for details
measure: Concentration at Time of Tumor Progression (Cprog) of Emactuzumab According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
timeFrame: At time of PD (up to 2 years)
measure: Concentration of Emactuzumab at Time of Tumor Response (Complete or Partial Response) According to RECIST v1.1
timeFrame: At time of tumor response (up to 2 years)
measure: Concentration of Emactuzumab at Time of Infusion-Related Reaction (IRR) or Hypersensitivity Reaction
timeFrame: At time of IRR or hypersensitivity reaction (up to 2 years)
measure: Cmax of RO7009789
timeFrame: 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)
measure: Ctrough of RO7009789
timeFrame: PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years)
measure: AUC of RO7009789
timeFrame: 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)
measure: CL of RO7009789
timeFrame: 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)
measure: Vss of RO7009789
timeFrame: 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)
measure: Accumulation Ratio of RO7009789
timeFrame: 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)
measure: T1/2 of RO7009789
timeFrame: 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)
measure: Total Tumor-Associated Macrophages (TAMs) in Paired-Tumor Biopsies
timeFrame: Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years)
measure: Total Dermal Macrophages in Paired-Skin Biopsies
timeFrame: Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years)
measure: Levels of Functional Tumor-Infiltrating Lymphocytes
timeFrame: Baseline; on D1 of C2 (cycle = 3 weeks); and optionally at time of PD (up to 2 years)
measure: Circulating Colony-Stimulating Factor (CSF)-1 Serum Levels
timeFrame: 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)
measure: Total Monocyte Count in Peripheral Blood
timeFrame: 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)
measure: Total Dendritic Cell Count in Peripheral Blood
timeFrame: 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)
measure: Circulating Cluster of Differentiation (CD) 4 T Cell Count in Peripheral Blood
timeFrame: 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)
measure: Circulating CD8 T Cell Count in Peripheral Blood
timeFrame: 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)
measure: Circulating B Cell Count in Peripheral Blood
timeFrame: 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)
measure: Metabolic Response of Target Lesions Assessed as the Change in Maximum Standardized Uptake Value (SUVmax) on [18F]-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
timeFrame: Baseline; on D15 of C1; PrD (+/- 4 days) on D1 of C3 (cycle = 3 weeks)
measure: Percentage of Participants by Best Overall Response as Assessed by RECIST v1.1
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
measure: Percentage of Participants with Overall Response as Assessed by RECIST v1.1
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
measure: Progressive-Free Survival (PFS) as Assessed by RECIST v1.1
timeFrame: From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall)
measure: Duration of Response (DOR) as Assessed by RECIST v1.1
timeFrame: From OR until PD; assessed every 6 weeks (up to 2 years overall)
measure: Percentage of Participants with Clinical Benefit as Assessed by RECIST v1.1
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
measure: Percentage of Participants by Best Overall Response as Assessed by Modified RECIST
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
measure: Percentage of Participants with Overall Response as Assessed by Modified RECIST
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
measure: Progressive-Free Survival (PFS) as Assessed by Modified RECIST
timeFrame: From Baseline until death or PD; assessed every 6 weeks (up to 2 years overall)
measure: Duration of Response (DOR) as Assessed by Modified RECIST
timeFrame: From OR until PD; assessed every 6 weeks (up to 2 years overall)
measure: Percentage of Participants with Clinical Benefit as Assessed by Modified RECIST
timeFrame: Baseline; every 6 weeks until PD (up to 2 years); at 28 days after last dose (up to 2 years overall)
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University Pennsylvania Hospital
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave Roussy; Sitep
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.