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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05129280
• Other study ID #: BE43244
• Secondary ID: 2021-000624-35
• Status: Terminated
• Phase: Phase 1
• Start date: January 25, 2022
• Est. completion date: July 12, 2023

Study information

• Verified date: August 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: July 12, 2023
• Est. primary completion date: July 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• RO7444973
RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.
• 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.

Locations

Country	Name	City	State
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Denmark	Rigshospitalet; Fase 1 Enhed - Onkologi	København Ø
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
United Kingdom	Royal Marsden Hospital - Institute of Cancer Research - Sutton	Sutton
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Number of Participants With Dose-limiting Toxicities (DLTs)		From start of treatment up to 21-28 days
Secondary	Objective Response Rate (ORR)		From baseline up to 12 months
Secondary	Disease Control Rate (DCR)		From baseline up to 12 months
Secondary	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)
Secondary	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)
Secondary	Overall Survival (OS)		From baseline to death from any cause (up to 40 months)
Secondary	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)
Secondary	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)