Clinical trial NCT05129280: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-11-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: From start of treatment up to 21-28 days
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From baseline up to 12 months
measure: Disease Control Rate (DCR)
timeFrame: From baseline up to 12 months
measure: Duration of Response (DoR)
timeFrame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 40 months)
measure: Progression-free Survival (PFS)
timeFrame: From baseline to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)
measure: Overall Survival (OS)
timeFrame: From baseline to death from any cause (up to 40 months)
measure: Pharmacokinetics (PK): Serum Concentration of RO7444973 Over Time
timeFrame: From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)
measure: Change from Baseline in Percentage of Participants Positive for Anti-drug Antibodies (ADA) to RO7444973
timeFrame: From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: København Ø
country: Denmark
facility: Rigshospitalet; Fase 1 Enhed - Onkologi
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Institute of Cancer Research - Sutton
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: