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

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety, tolerability and preliminary anti-tumor activity of RO7296682 in combination with Atezolizumab in participants with advanced solid tumors.

Official Title
-----------------
An Open-Label, Multicenter, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of RO7296682 in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Drug: RO7296682
* Drug: Atezolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Diagnosis of advanced and/or metastatic solid tumors who have progressed on a standard therapy, are intolerant to standard of care (SoC), and/or and non-amenable to SoC. Participants whose tumors have known sensitizing mutations 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 and atezolizumab, 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. 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 and atezolizumab 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. 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br>Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682 with a fixed dose of Atezolizumab, every three weeks (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>Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Part II<br>Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I. Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab. | Drug: RO7296682<br>* RO7296682 will be administered as per the schedules specified in the respective arms.<br>Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Part III (Exploratory)<br>Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I and if clinical activity is seen in this trial or in the single agent study (WP41188). Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab at the dosing regimen established in Part I. | Drug: RO7296682<br>* RO7296682 will be administered as per the schedules specified in the respective arms.<br>Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) |  | Up to 31 months | 
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) |  | Up to 31 months | 
| Objective Response Rate (ORR) (Part II and III only) |  | Up to 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) (Part I only) |  | Up to 31 months | 
| Disease Control Rate (DCR) |  | Up to 31 months | 
| Duration of Response (DoR) |  | Up to 31 months | 
| Progression-Free Survival (PFS) |  | Up to 31 months | 
| Overall Survival (OS) |  | Up to 31 months | 
| Area under the Curve (AUC) of RO7296682 |  | Up to 31 months | 
| Minimum Concentration (Cmin) of RO7296682 |  | Up to 31 months | 
| Maximum Concentration (Cmax) of RO7296682 |  | Up to 31 months | 
| Time of maximum concentration (Tmax) of RO7296682 |  | Up to 31 months | 
| Volume of distribution at steady-state conditions (Vss) of RO7296682 |  | Up to 31 months | 
| Half-life (t 1/2) of RO7296682 |  | Up to 31 months | 
| Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline |  | Up to 31 months | 
| Treatment-induced changes in Teff/Treg (T-effector cell; T-regulatory cell) ratio in blood and/or tumor as compared to baseline |  | Up to 31 months | 

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