A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors.

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.

Detailed Description
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A Phase 1, open-label, dose-escalation study designed to evaluate the safety and tolerability of RO7296682 in participants with advanced and/or metastatic solid tumors. RO7296682 will be administered by intravenous (IV) infusion every 3 weeks. This entry-into-human study is divided into a dose-escalation stage (Part A) and a dose expansion stage (Part B).

Official Title
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An Open-label, Multicenter Phase 1 Study to Evaluate Safety, Tolerability, PK (Pharmacokinetics)/PD (Pharmacodynamics) of RO7296682, a T-regulatory Cell Depleting Antibody in Participants With Advanced and/or Metastatic Solid Tumors.

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: RO7296682


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced and/or metastatic solid tumors who have progressed on all standard therapies, are intolerant to Standard-Of-Care (SOC), and/or are non-amenable to SOC. Participants whose tumors have known sensitizing mutation must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy. Measurable disease according to RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Able to provide the most recent archival tumor tissue samples. Adequate cardiovascular, haematological, liver and renal function. Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen. Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods. Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm. Exclusion Criteria: Pregnancy, lactation, or breastfeeding. Known hypersensitivity to any of the components of RO7296682, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. History or clinical evidence of central nervous system (CNS) primary tumors or metastases. Participants with another invasive malignancy in the last two years. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results. Participants with known active or uncontrolled infection. Positive HIV test at screening. Positive for Hepatitis B and C. Vaccination with live vaccines within 28 days prior to C1D1. Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 infusion. Participants with wound healing complications. Dementia or altered mental status that would prohibit informed consent. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms). Active or history of autoimmune disease or immune deficiency. Prior treatment with CPIs (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved. Prior treatment with a CC chemokine receptor 4 (CCR4)-targeting (e.g. mogamulizumab) or a CD25-targeting agent (e.g. basiliximab) is prohibited. Treatment with standard radiotherapy, any chemotherapeutic agent, targeted therapy or treatment with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) within 28 days or 5 half-lives of the drug (whichever is shorter), prior to the first RO7296882 administration on C1D1. Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy (for which no wash out period is required).

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682. RO7296682 will be administered by intravenous (IV) infusion in a three-weekly schedule (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined. | Drug: RO7296682<br>* RO7296682 will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Part B<br>Dose-Expansion: Will start once MTD/RP2D dose is defined in Part A. Participants will receive a fixed dose of RO7296682 at the dosing regimen established in part A (Q3W schedule). | Drug: RO7296682<br>* RO7296682 will be administered as per the schedules specified in the respective arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events | Severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | Up to 28 months | 
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) |  | 28 Days in Part A | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Up to 28 months | 
| Disease Control Rate (DCR) |  | Up to 28 months | 
| Duration of Response (DOR) |  | Up to 28 months | 
| Progression-Free Survival (PFS) |  | Up to 28 months | 
| Area under the curve (AUC) of RO7296682 |  | Up to 28 months | 
| Minimum Concentration (Cmin) of RO7296682 |  | Up to 28 months | 
| Maximum Concentration (Cmax) of RO7296682 |  | Up to 28 months | 
| Clearance (CL) of RO7296682 |  | Up to 28 months | 
| Volume of distribution at steady-state conditions (Vss) of RO7296682 |  | Up to 28 months | 
| Half-life (t 1/2) of RO7296682 |  | Up to 28 months | 
| Time of maximum concentration (Tmax) of RO7296682 |  | Up to 28 months | 
| Incidence and titer of Anti-Drug Antibodies (ADA) during the study relative to the prevalence of ADA at baseline |  | Up to 28 months | 
| Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline |  | Up to 28 months | 
| Treatment-induced changes in Treg/Teff (T-regulatory cell; T-effector cell) ratio in blood and/or tumor as compared to baseline |  | Up to 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RG6292