We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Completed
First Posted : December 23, 2014
Last Update Posted : August 27, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 5, 2014
First Posted Date  ICMJE December 23, 2014
Last Update Posted Date August 27, 2020
Actual Study Start Date  ICMJE January 19, 2015
Actual Primary Completion Date August 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 21 days ]
  • Maximum Tolerated Dose (MTD) of Emactuzumab [ Time Frame: 21 days ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 3 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
  • Safety: Nature and frequency of dose-limiting toxicities [ Time Frame: Up to 21 days ]
  • Safety (composite outcome measure): Incidence, nature and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 [ Time Frame: Up to 3 years ]
  • Safety (composite outcome measure): Changes in vital signs, physical findings, and clinical laboratory results during and following study drugs administration [ Time Frame: At selected timepoints in study, up to 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • 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)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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)
  • 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)
  • 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)
  • 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) ]
  • Change From Baseline in Dermal Macrophages Levels in Paired Skin Biopsies at Specified Timepoints [ Time Frame: Baseline, D15 of C1 (Cycle Length=21 days) ]
  • 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)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
  • Pharmacokinetics (PK): Profile parameters of MPDL3280A - maximum serum concentration (Cmax), minimum serum concentration(Cmin); additional PK parameters as appropriate [ Time Frame: At selected timepoints in study, up to 3 years ]
  • Pharmacokinetics (PK): Profile parameters of RO5509554 - maximum serum concentration (Cmax), trough concentration (Ctrough), area under the concentration-time curve (AUC), total clearance (CL); additional PK parameters as appropriate [ Time Frame: At selected timepoints in study, up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Emactuzumab and Atezolizumab Administered in Combination in Participants With Advanced Solid Tumors
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Cancers
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Part 1 (Dose-finding): Emactuzumab + Atezolizumab
    Participants will receive escalating doses of emactuzumab along with atezolizumab every 3 weeks (q3w).
    Interventions:
    • Drug: Atezolizumab
    • Drug: Emactuzumab
  • 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Emactuzumab
Publications * Gomez-Roca C, Cassier P, Zamarin D, Machiels JP, Luis Perez Gracia J, Stephen Hodi F, Taus A, Martinez Garcia M, Boni V, Eder JP, Hafez N, Sullivan R, Mcdermott D, Champiat S, Aspeslagh S, Terret C, Jegg AM, Jacob W, Cannarile MA, Ries C, Korski K, Michielin F, Christen R, Babitzki G, Watson C, Meneses-Lorente G, Weisser M, Rüttinger D, Delord JP, Marabelle A. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade. J Immunother Cancer. 2022 May;10(5). pii: e004076. doi: 10.1136/jitc-2021-004076.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 17, 2020)
221
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2014)
110
Actual Study Completion Date  ICMJE August 21, 2020
Actual Primary Completion Date August 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02323191
Other Study ID Numbers  ICMJE BP29428
2014-002428-29 ( EudraCT Number )
RG7155 ( Other Identifier: Roche )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP