Clinical trial NCT02558140: A Dose Escalation Study of RO6874813 in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: An Open-Label, Multicenter, Dose-Escalation Phase I Study of RO6874813, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Percentage of Participants With Dose-Limiting Toxicity (DLT)
timeFrame: 28 days
measure: Part 1: Maximum Tolerated Dose (MTD) of RO6874813
timeFrame: 28 days
measure: Part 1: Recommended Phase 2 Dose (RP2D) of RO6874813
timeFrame: 28 days
measure: Parts 1 and 2: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to approximately 24 months
measure: Parts 1 and 2: Percentage of Participants With Anti-Drug Antibodies (ADAs)
timeFrame: Predose (Hour [Hr] 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame
measure: 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)
timeFrame: Baseline until disease progression (up to approximately 12 months)
measure: Part 3: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 3: Duration of Response (DoR) as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 3: Median Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 3: Percentage of Participants Who are Progression-Free at Months 3 as Determined by the Investigator Using RECIST v1.1
timeFrame: Month 3
measure: Part 3: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1
timeFrame: Month 6
measure: Part 3: Median Overall Survival (OS)
timeFrame: Baseline until death (up to approximately 24 months)
measure: Part 3: Percentage of Participants Who are Alive at Month 12
timeFrame: Month 12
Secondary outcomes:
measure: Parts 1, 2, and 3: Maximum Observed Serum Concentration (Cmax) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Minimum Observed Serum Concentration (Cmin) of RO6874813
timeFrame: 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)
measure: Parts 1, 2, and 3: Time to Reach Cmax (Tmax) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Half-Life (t1/2) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Area Under the Concentration-Time Curve (AUC) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Clearance (CL) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: AUC During One Dose Interval (AUCtau) of RO6874813
timeFrame: 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
measure: Parts 1, 2, and 3: Volume at Steady State (Vss) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Accumulation Ratio (RA) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: Parts 1, 2, and 3: Observed Steady-State Concentration at the End of a Dosing Interval (Ctrough) of RO6874813
timeFrame: Predose (Hr 0) up to approximately 12 months; please see outcome measure description for detailed time frame
measure: 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)
timeFrame: Baseline and 12 months
measure: Part 1 and 2: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 1 and 2: Percentage of Participants With Disease Control as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 1 and 2: DOR as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 1 and 2: Median PFS as Determined by the Investigator Using RECIST v1.1
timeFrame: Baseline up to approximately 12 months
measure: Part 1 and 2: Percentage of Participants Who are Progression-Free at Month 6 as Determined by the Investigator Using RECIST v1.1
timeFrame: Month 6
measure: Part 3: Percentage of Participants With AEs
timeFrame: Baseline up to approximately 24 months
measure: Part 3: Percentage of Participants With ADAs
timeFrame: Predose (Hr 0) on Day 1 up to approximately 12 months; please see outcome measure description for detailed time frame
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SCRI
state: Tennessee
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: