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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02760797
Recruitment Status : Completed
First Posted : May 4, 2016
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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).

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Emactuzumab Drug: RO7009789 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 9, 2016
Actual Primary Completion Date : April 6, 2018
Actual Study Completion Date : April 6, 2018
Arms and Interventions
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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 Name: 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 Name: RO5509554

Drug: RO7009789
RO7009789 will be administered IV every 3 weeks (every cycle).


Outcome Measures
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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 ]
    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)

  4. 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) ]
  5. 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 ]
    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)

  6. 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 ]
    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)

  7. 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 ]
    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)

  8. 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 ]
    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)

  9. 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 ]
    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)

  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. Ctrough of RO7009789 [ Time Frame: PrD (0 H) on D1 of C2 onwards (cycle = 3 weeks) until PD (up to 2 years) ]
  15. 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) ]
  16. 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) ]
  17. 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) ]
  18. 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) ]
  19. 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) ]
  20. 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) ]
  21. 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) ]
  22. 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) ]
  23. 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) ]
  24. 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) ]
  25. 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) ]
  26. 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) ]
  27. 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) ]
  28. 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) ]
  29. 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) ]
  30. 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) ]
  31. 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) ]
  32. 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) ]
  33. 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) ]
  34. 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) ]
  35. 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) ]
  36. 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) ]
  37. 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) ]
  38. Duration of Response (DOR) as Assessed by Modified RECIST [ Time Frame: From OR until PD; assessed every 6 weeks (up to 2 years overall) ]
  39. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02760797


Locations
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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
United States, Pennsylvania
University Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
Belgium
Cliniques Universitaires St-Luc
Bruxelles, Belgium, 1200
France
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France, 69373
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, France, 31059
Institut Gustave Roussy; Sitep
VILLEJUIF Cedex, France, 94805
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02760797    
Other Study ID Numbers: BP29427
2015-004348-21 ( EudraCT Number )
First Posted: May 4, 2016    Key Record Dates
Last Update Posted: May 22, 2018
Last Verified: May 2018