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| ID | Type | Description | Link |
|---|---|---|---|
| RG7386 | Other Identifier | Roche | |
| 2015-001889-26 | EudraCT Number |
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This first-in-human study consists of three parts. The primary purpose of Part 1 is to characterize the safety and tolerability of RO6874813 in participants with locally advanced and/or metastatic solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. In addition, the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) will be determined. In Part 2 the safety and tolerability of RO6874813 will continue to be characterized in participants with locally advanced and/or metastatic solid tumors known to be fibroblast activation protein-alpha positive (FAP+). In addition, treatment-induced efficacy of RO6874813 will be assessed by functional imaging and paired tumor biopsies. The primary purpose of Part 3 is to demonstrate anti-tumor activity of RO6874813 in participants with recurrent or metastatic FAP+ sarcomas.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Dose Escalation | Experimental | All participants will be given RO6874813 as a single low dose of 0.5 milligrams per kilogram (mg/kg) via intravenous (IV) infusion in a 7-day pharmacokinetic (PK) run-in period (Cycle 0). This is followed by dose escalation (Cycle 1) for which participants will receive escalating doses of RO6874813 (starting dose = 1 mg/kg) via IV infusion every week (qw) or every 2 weeks (Q2W) for 28 to 42 days to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). |
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| Part 2: Tumor Biopsy and Imaging | Experimental | The first 15 participants with fibroblast activation protein-alpha positive (FAP+) tumors will be treated at the RP2D and dosing schedule as determined in Part 1, and will undergo paired tumor biopsies for biomarker assessments. Up to 5 participants with FAP+ tumors will undergo baseline and on-treatment tumor biopsies for biomarker assessments at a dose below the RP2D. The dose for these participants can be escalated to RP2D after 4 weeks of treatment and upon completion of biomarker assessment. |
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| Part 3: Preliminary Efficacy Assessment | Experimental | Participants with locally advanced or metastatic non-resectable FAP+ sarcoma will be treated with RO6874813 at the RP2D and as per schedule determined upon completion of Part 1. Participants continuing treatment with RO6874813 beyond 36 weeks will enter the extension phase of Part 3 and will be monitored for disease status and clinical safety per routine standard of care. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO6874813 | Biological | RO6874813 will be administered at a single low dose of 0.5 mg/kg via IV infusion in a 7- day PK run-in period (Cycle 0). Dose level for RO6874813 will be escalated to determine MTD and RP2D for RO6874813. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT) | 28 days | |
| Part 1: Maximum Tolerated Dose (MTD) of RO6874813 | 28 days | |
| Part 1: Recommended Phase 2 Dose (RP2D) of RO6874813 | 28 days | |
| Parts 1 and 2: Percentage of Participants With Adverse Events (AEs) | Baseline up to approximately 24 months | |
| Parts 1 and 2: Percentage of Participants With Anti-Drug Antibodies (ADAs) | Q2W (1 cycle=14 days): Predose (Hr 0) on Day 1 of Run-in period (Part 1 only), Cycles 1, 3, 5, then every 2 cycles (up to approximately 12 months); QW (1 cycle=7 days): Predose on Day 1 of Run-in period (Part 1 only), Cycles 1, 2, 5, then every 2 cycles (up to approximately 12 months) | Predose (Hour [Hr] 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame |
| Part 3: Percentage of Participants With Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Baseline until disease progression (up to approximately 12 months) | |
| Part 3: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months | |
| Part 3: Duration of Response (DoR) as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1, 2, and 3: Maximum Observed Serum Concentration (Cmax) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), End of Infusion (EoI) (infusion length less than or equal to [<=] 1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) |
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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 |
|---|---|---|---|---|---|---|
| SCRI | Nashville | Tennessee | 37203 | United States | ||
| Centre Leon Berard; Departement Oncologie Medicale |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| RO6874813 | Biological | RO6874813 at RP2D will be administered by IV infusion as per dosing schedule determined in Part 1. |
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| Part 3: Median Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Part 3: Percentage of Participants Who are Progression-Free at Months 3 as Determined by the Investigator Using RECIST v1.1 | Month 3 |
| Part 3: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1 | Month 6 |
| Part 3: Median Overall Survival (OS) | Baseline until death (up to approximately 24 months) |
| Part 3: Percentage of Participants Who are Alive at Month 12 | Month 12 |
| Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Minimum Observed Serum Concentration (Cmin) of RO6874813 | QW or Q2W: Predose (Hr 0) on Day 1 in Cycles 0, 1, 2, 3, 4, 5, 6, 7, and every 2 cycles thereafter (up to approximately 12 months) |
| Parts 1, 2, and 3: Time to Reach Cmax (Tmax) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Half-Life (t1/2) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Area Under the Concentration-Time Curve (AUC) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Clearance (CL) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: AUC During One Dose Interval (AUCtau) of RO6874813 | Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycle 1 and QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycle 1 |
| Parts 1, 2, and 3: Volume at Steady State (Vss) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Accumulation Ratio (RA) of RO6874813 | Run-in Period (Part 1 only): Predose (Hr 0), EoI (infusion length <=1.5 hrs), 24, 48, 72 (only for QW), and 96 hrs after EoI. Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose and EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months). QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycles 1 and 4; Predose, EoI, and 2 hrs after EoI in Cycles 2 and 6; Predose, EoI in Cycles 3, 5, 7, and every 2 cycles thereafter (up to approximately 12 months) | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Observed Steady-State Concentration at the End of a Dosing Interval (Ctrough) of RO6874813 | Q2W (1 cycle=14 days): Predose, EoI, 2, 6, 24, 72, 96, 168, and 240 hrs after EoI in Cycle 1. QW (1 cycle=7 days): Predose, EoI, 2, 6, 24, 48, 72, and 96 hrs after EoI in Cycle 1 | Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame |
| Parts 1, 2, and 3: Change from Baseline in Body Weight Corrected Maximum Standardized Uptake Volume (SUVmax) as Measured by 2-[18F]Fluoro-2-Deoxyglucose Positron Emission Tomography ([18F]-FDG PET) | Baseline and 12 months |
| Part 1 and 2: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Part 1 and 2: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Part 1 and 2: DOR as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Part 1 and 2: Median PFS as Determined by the Investigator Using RECIST v1.1 | Baseline up to approximately 12 months |
| Part 1 and 2: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1 | Month 6 |
| Part 3: Percentage of Participants With AEs | Baseline up to approximately 24 months |
| Part 3: Percentage of Participants With ADAs | Q2W (1 cycle=14 days): Predose (Hr 0) on Day 1 of Run-in period (Part 1 only), Cycles 1, 3, 5, then every 2 cycles (up to approximately 12 months); QW (1 cycle=7 days): Predose on Day 1 of Run-in period (Part 1 only), Cycles 1, 2, 5, then every 2 cycles (up to approximately 12 months) | Predose (Hr 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame |
| Lyon |
| 69373 |
| France |
| Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | 08035 | Spain |
| START Madrid. Centro Integral Oncologico Clara Campal; CIOCC | Madrid | 28050 | Spain |