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

NCT ID: NCT02558140

Last Updated: 2018-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-11
• Study Completion Date: 2017-11-06

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.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation

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).

Group Type: EXPERIMENTAL

RO6874813

Intervention Type: 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.

Part 2: Tumor Biopsy and Imaging

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.

Group Type: EXPERIMENTAL

RO6874813

Intervention Type: BIOLOGICAL

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

Part 3: Preliminary Efficacy Assessment

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.

Group Type: EXPERIMENTAL

RO6874813

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: BIOLOGICAL

RO6874813

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

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

SCRI

Nashville, Tennessee, United States

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, , Spain

Countries

United States; France; Spain

Other Identifiers

RG7386

Identifier Type: OTHER

Identifier Source: secondary_id

2015-001889-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP29773

Identifier Type: -

Identifier Source: org_study_id