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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02558140
• Other study ID #: BP29773
• Secondary ID: RG73862015-00188
• Status: Completed
• Phase: Phase 1
• First received: September 15, 2015
• Last updated: April 3, 2018
• Start date: October 11, 2015
• Est. completion date: November 6, 2017

Study information

• Verified date: April 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: November 6, 2017
• Est. primary completion date: November 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Biological:
• RO6874813
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.
• RO6874813
RO6874813 at RP2D will be administered by IV infusion as per dosing schedule determined in Part 1.

Locations

Country	Name	City	State
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid
United States	SCRI	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT)		28 days
Primary	Part 1: Maximum Tolerated Dose (MTD) of RO6874813		28 days
Primary	Part 1: Recommended Phase 2 Dose (RP2D) of RO6874813		28 days
Primary	Parts 1 and 2: Percentage of Participants With Adverse Events (AEs)		Baseline up to approximately 24 months
Primary	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
Primary	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)
Primary	Part 3: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1		Baseline up to approximately 12 months
Primary	Part 3: Duration of Response (DoR) as Determined by the Investigator Using RECIST v1.1		Baseline up to approximately 12 months
Primary	Part 3: Median Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1		Baseline up to approximately 12 months
Primary	Part 3: Percentage of Participants Who are Progression-Free at Months 3 as Determined by the Investigator Using RECIST v1.1		Month 3
Primary	Part 3: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1		Month 6
Primary	Part 3: Median Overall Survival (OS)		Baseline until death (up to approximately 24 months)
Primary	Part 3: Percentage of Participants Who are Alive at Month 12		Month 12
Secondary	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)	Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1 and 2: DOR as Determined by the Investigator Using RECIST v1.1		Baseline up to approximately 12 months
Secondary	Part 1 and 2: Median PFS as Determined by the Investigator Using RECIST v1.1		Baseline up to approximately 12 months
Secondary	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
Secondary	Part 3: Percentage of Participants With AEs		Baseline up to approximately 24 months
Secondary	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