Solid Cancers
Conditions
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.
Interventions
DRUGAtezolizumab
Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w.
DRUGEmactuzumab
Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 3 years |
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | 21 days |
| Maximum Tolerated Dose (MTD) of Emactuzumab | 21 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) 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 | 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) 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) | 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 | 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) |
| Maximum Observed Plasma Concentration (Cmax) of Emactuzumab | 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) |
| 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 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 | 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) | — |
| 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) | — |
| 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) | — |
Countries
Belgium, France, Spain, United States
Outcome results
None listed