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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-002428-29 | EudraCT Number | ||
| RG7155 | Other Identifier | Roche |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 (Dose-finding): Emactuzumab + Atezolizumab | Experimental | Participants will receive escalating doses of emactuzumab along with atezolizumab every 3 weeks (q3w). |
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| Part 2 (Expansion): Emactuzumab + Atezolizumab | Experimental | Participants will receive emactuzumab at or below the MTDs for the combination treatments that are determined during Part 1 along with atezolizumab. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | 21 days | |
| Maximum Tolerated Dose (MTD) of Emactuzumab | 21 days | |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Emactuzumab | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale Cancer Center; Medical Oncology | New Haven | Connecticut | 06520 | United States | ||
| Massachusetts General Hospital. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35577503 | Derived | Gomez-Roca C, Cassier P, Zamarin D, Machiels JP, Perez Gracia JL, 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, Ruttinger D, Delord JP, Marabelle A. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naive or experienced for immune checkpoint blockade. J Immunother Cancer. 2022 May;10(5):e004076. doi: 10.1136/jitc-2021-004076. |
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| Emactuzumab | Drug | Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg. |
|
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| predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) |
| Maximum Observed Plasma Concentration (Cmax) of Atezolizumab | 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 | 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 | 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 | 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) | predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) |
| Total Clearance (CL) of Emactuzumab | 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 | 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 | 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 | 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) | 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) | predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) |
| Emactuzumab Concentration at the Time of Tumor Response (Complete Response/Partial Response) | 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) | predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) |
| Emactuzumab Concentration at the Time of Infusion-related Reaction (IRR) or Hypersensitivity Reaction | 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) | predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description) |
| Change From Baseline in Tumor-Associated Macrophages (TAMs) Levels in Paired-Tumor Biopsies at Specified Timepoints | 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 | 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 | 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) | Baseline up to approximately 3 years (detailed timeframe provided in measure description) |
| Percentage of Participants With Anti-therapeutic Antibodies to Emactuzumab | 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 | 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 | 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 | 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 | 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 | Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years) |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Dana Farber - Harvard | Boston | Massachusetts | United States |
| Memorial Sloan-Kettering Cancer Center Breast & Imaging Center | New York | New York | 10065 | United States |
| Cliniques Universitaires St-Luc | Brussels | 1200 | Belgium |
| Centre Leon Berard; Departement Oncologie Medicale | Lyon | 69373 | France |
| Institut Claudius Regaud; Departement Oncologie Medicale | Toulouse | 31059 | France |
| Institut Gustave Roussy; Departement Oncologie Medicale | Villejuif | 94805 | France |
| Clinica Universitaria de Navarra; Servicio de Oncologia | Pamplona | Navarre | 31008 | Spain |
| Hospital del Mar; Servicio de Oncologia | Barcelona | 08003 | Spain |
| Centro Integral Oncológico Clara Campal Ensayos Clínicos START | Madrid | 28050 | Spain |
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| C000602304 | emactuzumab |
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