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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: RO7444973
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: Single Participant Cohort (SPC) Dose Escalation<br>In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level. | Drug: RO7444973<br>* RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.<br>Drug: Tocilizumab<br>* 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.<br>* Other names: Actemra, RoActemra;|
| Experimental: Part II: Multiple Participant Cohort (MPC) Dose Escalation<br>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. | Drug: RO7444973<br>* RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.<br>Drug: Tocilizumab<br>* 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.<br>* Other names: Actemra, RoActemra;|
| Experimental: Part III: Recommended Phase 2 Dose (RP2D) Expansion<br>Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III. | Drug: RO7444973<br>* RO7444973 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective cohort.<br>Drug: Tocilizumab<br>* 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.<br>* Other names: Actemra, RoActemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |