Solid Tumors
Conditions
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.
Interventions
DRUGRO7444973
RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.
DRUGTocilizumab
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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) |
| Objective Response Rate (ORR) | From baseline up to 12 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) |
| Overall Survival (OS) | From baseline to death from any cause (up to 40 months) |
| Disease Control Rate (DCR) | From baseline up to 12 months |
Countries
Australia, Belgium, Denmark, Spain, United Kingdom, United States
Outcome results
None listed