A Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-tumor Activity of RO7444973 in Participants With Unresectable and/or Metastatic MAGE-A4-positive Solid Tumors

An Open-label, Multicenter, Phase I Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-tumor Activity of RO7444973 in Participants With Unresectable and/or Metastatic MAGE-A4-positive Solid Tumors

This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy dose-escalation and dose expansion study of RO7444973.The aim of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RO7444973 in participants with unresectable and/or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive, solid tumors, carrying the HLA-A*02:01 allele.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Tocilizumab; Drug: RO7444973

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet; Fase 1 Enhed - Onkologi
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro-CIOCC
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital - Institute of Cancer Research - Sutton
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Unresectable and/or metastatic solid tumors that have received standard-of-care (SOC) therapies previously and have no other SOC options available
• Confirmed HLA-A*02:01 haplotype
• Confirmed MAGE-A4 expression
• Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Life expectancy of >/=12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absence of rapid disease progression, threat to vital organs or non-irradiated lesions >2 cm in diameter at critical sites
• No significant ongoing toxicity from prior anticancer treatment
• Adequate hematological function
• Adequate liver function
• Adequate renal function
• If applicable, willingness to use contraceptive measures.

Key Exclusion Criteria:

• History or clinical evidence of CNS primary tumors or metastases
• Another invasive malignancy in the last 2 years
• Uncontrolled hypertension
• Significant cardiovascular disease
• Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic or other infection
• Current or past history of CNS disease
• Dementia or altered mental status that would prohibit informed consent
• Active auto-immune disease or flare within 6 months prior to start of study treatment
• Expected need for regular immunosuppressive therapy or with systemic corticosteroids
• Insufficient washout from prior anti-cancer therapy
• Prior treatment with a bispecific T-cell engaging or adoptive cell therapy.

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 I: Single Participant Cohort (SPC) Dose Escalation; In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.	Drug: Tocilizumab; Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.; Other Names: Actemra, RoActemra; Drug: RO7444973; RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.
Experimental: Part II: Multiple Participant Cohort (MPC) Dose Escalation; In Part II, RO7444973 is administered IV Q3W at a fixed dose in multiple participants per dose level. Step-up dosing may also be explored.	Drug: Tocilizumab; Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.; Other Names: Actemra, RoActemra; Drug: RO7444973; RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.
Experimental: Part III: Recommended Phase 2 Dose (RP2D) Expansion; Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.	Drug: Tocilizumab; Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.; Other Names: Actemra, RoActemra; Drug: RO7444973; RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)
Number of Participants With Dose-limiting Toxicities (DLTs)	From start of treatment up to 21-28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	From baseline up to 12 months
Disease Control Rate (DCR)	From baseline up to 12 months
Duration of Response (DoR)	From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 40 months)
Progression-free Survival (PFS)	From baseline to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)
Overall Survival (OS)	From baseline to death from any cause (up to 40 months)
Pharmacokinetics (PK): Serum Concentration of RO7444973 Over Time	From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)
Change from Baseline in Percentage of Participants Positive for Anti-drug Antibodies (ADA) to RO7444973	From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 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): January 25, 2022
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): July 12, 2023

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BE43244; 2021-000624-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data 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/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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