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Completed

NCT Number: NCT02558140

A Dose Escalation Study of RO6874813 in Participants With Locally Advanced or Metastatic Solid Tumors

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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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Centre Leon Berard; Departement Oncologie Medicale, Lyon, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Part 1: Participants with histologically/cytologically confirmed locally advanced or metastatic, non-resectable solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists
  • Part 2: Participants with histologically/ cytologically confirmed locally advanced or metastatic, non-resectable solid tumors known to be FAP+ whose disease has progressed despite standard therapy or for whom no standard therapy exists
  • Part 3: Participants with histologically confirmed recurrent or metastatic, non-resectable confirmed FAP+ sarcoma with two or fewer prior regimens for advanced disease
  • All participants must have tumor tissue that can be imaged for pharmacodynamic assessments and from which a pre- and on-treatment biopsy can be safely obtained
  • An archival tumor sample must be available for retrospective FAP expression analysis
  • Measurable disease as determined by RECIST v1.1
  • World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
  • Recovery from all reversible AEs of previous anti-cancer therapies to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1, except for alopecia (any grade) and Grade <=2 sensory peripheral neuropathy
  • Negative pregnancy test

Exclusion criteria

  • Primary central nervous (CNS) tumors or CNS tumor involvement
  • Major surgery or any other prior anti-cancer treatment within 4 weeks prior to study Day 1.
  • Received wide-field radiotherapy <= 4 weeks or limited-field radiotherapy <=2 weeks prior to starting study drug
  • Known hypersensitivity to any of the components of RO6874813 or to the contrast agents used in the study
  • Another invasive malignancy in the last 2 years except for those with a minimal risk of metastasis or death
  • Any other conditions or diseases that would contraindicate participation in the clinical study because of safety concerns or compliance with clinical study procedures

Treatment and study plan

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.

Primary outcomes

  1. Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT)

    Time frame: 28 days

  2. Part 1: Maximum Tolerated Dose (MTD) of RO6874813

    Time frame: 28 days

  3. Part 1: Recommended Phase 2 Dose (RP2D) of RO6874813

    Time frame: 28 days

  4. Parts 1 and 2: Percentage of Participants With Adverse Events (AEs)

    Time frame: Baseline up to approximately 24 months

  5. Parts 1 and 2: Percentage of Participants With Anti-Drug Antibodies (ADAs)

    Time frame: Predose (Hour [Hr] 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  6. 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)

    Time frame: Baseline until disease progression (up to approximately 12 months)

  7. Part 3: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  8. Part 3: Duration of Response (DoR) as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  9. Part 3: Median Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  10. Part 3: Percentage of Participants Who are Progression-Free at Months 3 as Determined by the Investigator Using RECIST v1.1

    Time frame: Month 3

  11. Part 3: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1

    Time frame: Month 6

  12. Part 3: Median Overall Survival (OS)

    Time frame: Baseline until death (up to approximately 24 months)

  13. Part 3: Percentage of Participants Who are Alive at Month 12

    Time frame: Month 12

Secondary outcomes

  1. Parts 1, 2, and 3: Maximum Observed Serum Concentration (Cmax) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  2. Parts 1, 2, and 3: Minimum Observed Serum Concentration (Cmin) of RO6874813

    Time frame: 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)

  3. Parts 1, 2, and 3: Time to Reach Cmax (Tmax) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  4. Parts 1, 2, and 3: Half-Life (t1/2) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  5. Parts 1, 2, and 3: Area Under the Concentration-Time Curve (AUC) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  6. Parts 1, 2, and 3: Clearance (CL) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  7. Parts 1, 2, and 3: AUC During One Dose Interval (AUCtau) of RO6874813

    Time frame: 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

  8. Parts 1, 2, and 3: Volume at Steady State (Vss) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  9. Parts 1, 2, and 3: Accumulation Ratio (RA) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

  10. Parts 1, 2, and 3: Observed Steady-State Concentration at the End of a Dosing Interval (Ctrough) of RO6874813

    Time frame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame

    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

  11. 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)

    Time frame: Baseline and 12 months

  12. Part 1 and 2: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  13. Part 1 and 2: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  14. Part 1 and 2: DOR as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  15. Part 1 and 2: Median PFS as Determined by the Investigator Using RECIST v1.1

    Time frame: Baseline up to approximately 12 months

  16. Part 1 and 2: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1

    Time frame: Month 6

  17. Part 3: Percentage of Participants With AEs

    Time frame: Baseline up to approximately 24 months

  18. Part 3: Percentage of Participants With ADAs

    Time frame: Predose (Hr 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame

    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)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

An Open-Label, Multicenter, Dose-Escalation Phase I Study of RO6874813, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Sep 23, 2015
Registry last updated
Apr 4, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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