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

Roche

Status and phase: Terminated; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Tocilizumab; Drug: RO7444973

Study type: Interventional

Funder types: Industry

Identifiers

NCT05129280

BE43244

2021-000624-35 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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23 participants in 3 patient groups

Part I: Single Participant Cohort (SPC) Dose Escalation

Experimental group

Description:

In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.

Treatment:

Drug: Tocilizumab

Drug: RO7444973

Part II: Multiple Participant Cohort (MPC) Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Drug: RO7444973

Part III: Recommended Phase 2 Dose (RP2D) Expansion

Experimental group

Description:

Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.

Treatment:

Drug: Tocilizumab

Drug: RO7444973