A Study to Evaluate Safety, Pharmacokinetics and Anti-Tumor Activity of RO7300490, as Single Agent or in Combination With Atezolizumab in Participants With Advanced Solid Tumors

An Open-Label, Multicenter, Dose-Escalation and Expansion, Phase I Study to Evaluate Safety, Pharmacokinetics, And Anti-Tumor Activity of RO7300490, A Fibroblast Activation Protein-α (FAP) Targeted CD40 Agonist, as Single Agent or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: [Part 1] Dose-Escalation of RO7300490 as a single agent; [Part 2] Dose-Escalation of RO7300490 in combination with atezolizumab and [Part 3] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: RO7300490; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet; Fase 1 Enhed - Onkologi
• France
  • Villejuif, France, 94805
    • Gustave Roussy
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra Madrid; Servicio de Oncología
  • Madrid, Spain, 28040
    • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital; Edinburgh Cancer Center
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas Hospital; OHCT Clinical Trials
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust; Experimental Cancer Medicine Team

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Life expectancy of >= 12 weeks.
• Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy.
• Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Agreement to provide protocol-specific biopsy material.
• Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<1.
• Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.

Exclusion Criteria:

• Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met.
• Active second invasive malignancy within two years prior to screening.
• Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start.
• Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Active or history of autoimmune disease.
• Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation.
• Pregnancy, lactation or breastfeeding.
• Dementia or altered mental status that would prohibit informed consent.
• Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment.
• Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation (RO7300490 Monotherapy); Participants will receive escalating doses of RO7300490 intravenously (IV) as a single agent for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.	Drug: RO7300490; Participants will receive RO7300490, as described in the Arm Descriptions.
Experimental: Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy); Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.	Drug: RO7300490; Participants will receive RO7300490, as described in the Arm Descriptions.; Drug: Atezolizumab; Participants will receive Atezolizumab, as described in the Arm Descriptions.
Experimental: Part 3: Dose Expansion (Disease-specific Expansion(s)); Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent.	Drug: RO7300490; Participants will receive RO7300490, as described in the Arm Descriptions.; Drug: Atezolizumab; Participants will receive Atezolizumab, as described in the Arm Descriptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2)	Up to 36 months
Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2)	Up to 36 months
Objective Response Rate (ORR) (Part 3)	Up to 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3)	Up to 48 months
Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3)	Up to 48 months
Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3)	Up to 48 months
Clearance (CL) of RO7300490 (Parts 1, 2 and 3)	Up to 48 months
Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3)	Up to 48 months
Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3)	Up to 48 months
Objective Response Rate (ORR) (Parts 1 and 2)	Up to 48 months
Disease Control Rate (DCR) (Parts 1, 2 and 3)	Up to 48 months
Duration of Response (DOR) (Parts 1, 2 and 3)	Up to 48 months
Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3)	Up to 48 months
Percentage of Participants With Adverse Events (AEs) (Part 3)	Up to 48 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2021
• Primary Completion (Actual): January 18, 2024
• Study Completion (Actual): January 18, 2024

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: WP42627; 2020-004489-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No