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A Study of Emactuzumab and Atezolizumab 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: NCT02323191
Recruitment Status : Active, not recruiting
First Posted : December 23, 2014
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:

This Phase 1, open-label, multicenter, global study will evaluate the safety, pharmacokinetics, and activity of emactuzumab and atezolizumab administered in combination in participants with selected locally advanced or metastatic solid tumors that are not amenable to standard treatment.

Participants who receive emactuzumab and atezolizumab will continue to receive study drug as long as they experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data, biopsy results (if available), and clinical status, or withdrawal of consent.


Condition or disease Intervention/treatment Phase
Solid Cancers Drug: Atezolizumab Drug: Emactuzumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label, Multicenter, Dose Escalation Phase Ib Study With Expansion Phase to Evaluate the Safety, Pharmacokinetics, and Activity of RO5509554 (Emactuzumab) and MPDL3280A (Atezolizumab) Administered in Combination in Patients With Advanced Solid Tumors
Actual Study Start Date : January 19, 2015
Estimated Primary Completion Date : December 26, 2019
Estimated Study Completion Date : December 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 (Dose-finding): Emactuzumab + Atezolizumab
Participants will receive escalating doses of emactuzumab along with atezolizumab every 3 weeks (q3w).
Drug: Atezolizumab
Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w.
Other Name: MPDL3280A, TECENTRIQ

Drug: Emactuzumab
Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg.
Other Name: RO5509554

Experimental: Part 2 (Expansion): Emactuzumab + Atezolizumab
Participants will receive emactuzumab at or below the MTDs for the combination treatments that are determined during Part 1 along with atezolizumab.
Drug: Atezolizumab
Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w.
Other Name: MPDL3280A, TECENTRIQ

Drug: Emactuzumab
Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg.
Other Name: RO5509554




Primary Outcome Measures :
  1. Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 21 days ]
  2. Maximum Tolerated Dose (MTD) of Emactuzumab [ Time Frame: 21 days ]
  3. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 3 years ]

Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Emactuzumab [ Time Frame: predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) ]
    predose (-4 hours [h]) and 0.5h post end of infusion (90 minutes infusion) on Days (D) 1 of Cycle (C) 1, 2, 3, 4, 5, 6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)

  2. Maximum Observed Plasma Concentration (Cmax) of Atezolizumab [ Time Frame: predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days); 0.5h post end of infusion (60 minutes infusion) on D1 of C1; 120 days post last infusion (up to approximately 3 years) ]
  3. Minimum Observed Plasma Trough Concentration (Cmin) of Emactuzumab [ Time Frame: predose (-4 h) on D1 of C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years) ]
  4. Minimum Observed Plasma Trough Concentration (Cmin) of Atezolizumab [ Time Frame: predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days) ]
  5. Area under the Concentration-Time Curve (AUC) of Emactuzumab [ Time Frame: predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) ]
    predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)

  6. Total Clearance (CL) of Emactuzumab [ Time Frame: predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4 ]
  7. Volume of Distribution at Steady State (Vss) of Emactuzumab [ Time Frame: predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4 ]
  8. Accumulation Ratio (Rac) of Emactuzumab [ Time Frame: predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4 ]
  9. Terminal Elimination Half-life (t1/2) of Emactuzumab [ Time Frame: predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4 ]
  10. Emactuzumab Concentration at the time of Tumor Progression (Cprog) [ Time Frame: predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) ]
    predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)

  11. Emactuzumab Concentration at the Time of Tumor Response (Complete Response/Partial Response) [ Time Frame: predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) ]
    predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)

  12. Emactuzumab Concentration at the Time of Infusion-related Reaction (IRR) or Hypersensitivity Reaction [ Time Frame: predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) ]
    predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)

  13. Change From Baseline in Tumor-Associated Macrophages (TAMs) Levels in Paired-Tumor Biopsies at Specified Timepoints [ Time Frame: Baseline (predose [-4 h] on D1 of C2; Cycle Length=21 days), at disease progression (up to approximately 3 years) ]
  14. Change From Baseline in Dermal Macrophages Levels in Paired Skin Biopsies at Specified Timepoints [ Time Frame: Baseline, D15 of C1 (Cycle Length=21 days) ]
  15. Change From Baseline in Circulating Cluster of Differentiation (CD) 14DimCD16high Monocytes Levels in Peripheral Blood at Specified Timepoints [ Time Frame: Baseline up to approximately 3 years (detailed timeframe provided in measure description) ]
    Baseline (predose [-4 h] on D1 of C1), predose [-4 h] on D1 of C2, C3, C5, then every other cycle (Cycle Length=21 days) until disease progression (up to approximately 3 years); postdose on D2, D8, D15 of C1, C2; D4 or D5 of C1; 44 days post last infusion (up to approximately 3 years)

  16. Percentage of Participants With Anti-therapeutic Antibodies to Emactuzumab [ Time Frame: predose (-4 h) on D1 of C1, C2, C3, C4, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years), 44 and 120 days post last infusion, 28 day follow-up visit (up to approximately 3 years) ]
  17. Percentage of Participants With Anti-therapeutic Antibodies to Atezolizumab [ Time Frame: predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days; up to approximately 3 years), 120 days post last infusion (up to approximately 3 years) ]
  18. Percentage of Participants With Best Overall Response as Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years) ]
  19. Percentage of Participants With Best Overall Response as Determined Using Modified RECIST [ Time Frame: Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years) ]
  20. Percentage of Participants With Objective Response as Determined Using RECIST v1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years) ]
  21. Percentage of Participants With Objective Response as Determined Using Modified RECIST [ Time Frame: Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
  • Participants must have histologically confirmed diagnosis of locally advanced and/or metastatic triple negative breast cancer, ovarian cancer, bladder cancer, gastric cancer, or soft tissue sarcoma, with exceptions defined in the exclusion criteria
  • Measurable disease at baseline as per RECIST version 1.1
  • Life expectancy of greater than or equal to (>=) 16 weeks
  • Adequate bone marrow, liver, cardiac, and renal function
  • Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women less than or equal to (<=) 12 months post-menopause. Postmenopausal state is defined as amenorrhea for greater than (>) 12 months.

Exclusion Criteria:

  • Allergy or hypersensitivity to components of the emactuzumab formulation or to components of the atezolizumab formulation
  • Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening (within 28 days before C1D1) and 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 metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm) are completely excluded
  • Leptomeningeal disease
  • History of or active autoimmune disease
  • Evidence of significant, uncontrolled concomitant diseases, which could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm)
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the exceptions provided in the protocol
  • Prior corticosteroids as anti-cancer therapy within a minimum of 14 days of first receipt of study drug
  • Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade <=1 severity (Common Terminology Criteria for Adverse Events [CTCAE] v4.03, or later versions)
  • History of human immunodeficiency virus (HIV)
  • Participants with active hepatitis B, active hepatitis C, or active tuberculosis
  • Participant has had pulmonary embolism or any other thrombo-embolic event within 6 months prior to study entry
  • Participants has a history of hematological malignancy within the last 5 years prior to study entry
  • Treatment with systemic immunosuppressive medications - Pregnant or lactating women

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): NCT02323191


Locations
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United States, Connecticut
Yale Cancer Center; Medical Oncology
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Massachusetts General Hospital.
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber - Harvard
Boston, Massachusetts, United States
United States, New York
Memorial Sloan-Kettering Cancer Center Breast & Imaging Center
New York, New York, United States, 10065
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; Departement Oncologie Medicale
Villejuif, France, 94805
Spain
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarra, Spain, 31008
Hospital del Mar; Servicio de Oncologia
Barcelona, Spain, 08003
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
Madrid, Spain, 28050
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02323191     History of Changes
Other Study ID Numbers: BP29428
2014-002428-29 ( EudraCT Number )
RG7155 ( Other Identifier: Roche )
First Posted: December 23, 2014    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019

Additional relevant MeSH terms:
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Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs