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

An Open-Label, Multicenter, Dose-Escalation Phase I Study of RO6874813, Administered Intravenously in Patients 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.

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