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

Phase 1

Terminated

• Conditions: Solid Tumors
• Interventions: Drug: RO7444973; Drug: Tocilizumab

• Registration Number: NCT05129280
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-19
• Study First Submitted QC: 2021-11-19
• Study First Posted: 2021-11-22
• Study Start: 2022-01-25
• Primary Completion: 2023-07-12
• Study Completion: 2023-07-12
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-02
• Last Update Posted: 2023-08-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part I: Single Participant Cohort (SPC) Dose Escalation	RO7444973	In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
Part II: Multiple Participant Cohort (MPC) Dose Escalation	RO7444973	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.
Part III: Recommended Phase 2 Dose (RP2D) Expansion	RO7444973	Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.
Part I: Single Participant Cohort (SPC) Dose Escalation	Tocilizumab	In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
Part II: Multiple Participant Cohort (MPC) Dose Escalation	Tocilizumab	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.
Part III: Recommended Phase 2 Dose (RP2D) Expansion	Tocilizumab	Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (10)

UZ Antwerpen; 🇧🇪 Edegem, Belgium

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Peter Maccallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

UZ Gent; 🇧🇪 Gent, Belgium

UZ Leuven Gasthuisberg; 🇧🇪 Leuven, Belgium

Rigshospitalet; Fase 1 Enhed - Onkologi; 🇩🇰 København Ø, Denmark

Cliniques Universitaires St-Luc; 🇧🇪 Bruxelles, Belgium

Royal Marsden Hospital - Institute of Cancer Research - Sutton; 🇬🇧 Sutton, United Kingdom

Vall d?Hebron Institute of Oncology (VHIO), Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario HM Sanchinarro-CIOCC; 🇪🇸 Madrid, Spain