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
Overview
- Phase
- Phase 1
- Intervention
- RO7444973
- Conditions
- Solid Tumors
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 23
- Locations
- 10
- Primary Endpoint
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Part III: Recommended Phase 2 Dose (RP2D) Expansion
Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.
Intervention: RO7444973
Part I: Single Participant Cohort (SPC) Dose Escalation
In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
Intervention: RO7444973
Part I: Single Participant Cohort (SPC) Dose Escalation
In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
Intervention: Tocilizumab
Part II: Multiple Participant Cohort (MPC) Dose Escalation
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.
Intervention: RO7444973
Part II: Multiple Participant Cohort (MPC) Dose Escalation
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.
Intervention: Tocilizumab
Part III: Recommended Phase 2 Dose (RP2D) Expansion
Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)
Number of Participants With Dose-limiting Toxicities (DLTs)
Time Frame: From start of treatment up to 21-28 days
Secondary Outcomes
- 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))