A Study of RO7617991 in Patients With Locally Advanced or Metastatic MAGE-A4-Positive Solid Tumors

A Phase I, Open-Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of RO7617991 in HLA-A*02-Positive Patients With Locally Advanced and/or Metastatic MAGE-A4-Positive Solid Tumors

This study will evaluate the safety, tolerability, and pharmacokinetics of RO7617991, and will make a preliminary assessment of the anti-tumor activity of RO7617991 in human leukocyte antigen (HLA)-A*02 eligible patients with locally advanced or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive solid tumors.

Study Overview

• Status: Withdrawn
• Conditions: Solid Tumor, Adult; Refractory Cancer; Recurrent Cancer
• Intervention / Treatment: Drug: RO7617991; Drug: Tocilizumab

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Recruiting
      • Peter MacCallum Cancer Centre-Box Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Body weight ≥40 kilograms
• Life expectancy of at least 12 weeks
• Confirmed eligible HLA-A*02 genotype and tumor with confirmed MAGE-A4 expression
• Histologically confirmed locally advanced or metastatic solid tumor malignancy that has relapsed or is refractory to established therapies
• Measurable disease, according to RECIST v1.1
• Adequate hematologic and end-organ function
• Resolution to Grade ≤2 of all acute, clinically significant treatment-related toxicity from prior therapy
• An archival tumor tissue specimen or fresh baseline biopsy (when archival is not available) is required

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of RO7617991 or tocilizumab
• Clinically significant cardiopulmonary dysfunction
• Clinically significant liver disease
• Poorly controlled Type 2 diabetes mellitus
• Active hepatitis B or C infection
• Positive test for human immunodeficiency virus (HIV)
• History of allergic reactions to red meat or tick bites or known galactose-alpha-1,3-galactose (alpha-gal) hypersensitivity
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Symptomatic pleural effusion, pericardial effusion, or ascites or any prior procedural intervention for pleural effusion, pericardial effusion, or ascites within 6 weeks prior to enrollment
• Active or history of autoimmune disease or immune deficiency
• Treatment with systemic immunosuppressive medications
• Prior allogeneic stem cell or solid organ transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RO7617991 Dose Escalation and Expansion

Drug: RO7617991; RO7617991 will be administered by intravenous (IV) infusion. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.; Drug: Tocilizumab; Tocilizumab 8 mg/kg IV will be administered to patients when necessary to treat potential cytokine release syndrome (CRS), as described in the protocol.; Other Names: RO4877533; RoActemra®; Actemra®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events		From first dose until 90 days after the final dose of study treatment (up to approximately 3 years)
Number of Participants with Abnormal Values in Targeted Vital Signs	The targeted vital signs include pulse rate, respiratory rate, systolic and diastolic blood pressure, pulse oximetry, and body temperature.	From Baseline (predose) until 90 days after the final dose of study treatment (up to approximately 3 years)
Number of Participants with Abnormal Values in Clinical Laboratory Test Parameters		From Baseline (predose) until 90 days after the final dose of study treatment (up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of RO7617991 at Specific Timepoints		From first dose until 30 days after the final dose of study treatment (up to approximately 3 years)
Objective Response Rate (ORR), as Determined by the Investigator According to RECIST v1.1	RECIST v1.1 = Response Evaluation Criteria in Solid Tumors, Version 1.1	From Baseline until until radiographic disease progression or loss of clinical benefit (up to approximately 3 years)
Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1		From first occurrence of a confirmed objective response to disease progression or death, whichever occurs first (up to approximately 3 years)
Progression-Free Survival (PFS), as Determined by the Investigator According to RECIST v1.1		From enrollment to the first occurrence of disease progression or relapse or death, whichever occurs first (up to approximately 3 years)
Overall Survival (OS)		From enrollment to death from any cause (up to approximately 3 years)
Prevalence of Anti-Drug Antibodies (ADAs) to RO7617991 at Baseline and Incidence of ADAs to RO7617991 During the Study		Baseline (predose) and from first dose until 90 days after the final dose of study treatment (up to approximately 3 years)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: GO44669

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

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