A Study to Evaluate Safety, Pharmacokinetics and Anti-Tumor Activity of RO7300490, as Single Agent or in Combination With Atezolizumab in Participants With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: [Part 1] Dose-Escalation of RO7300490 as a single agent; [Part 2] Dose-Escalation of RO7300490 in combination with atezolizumab and [Part 3] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.

Official Title
-----------------
An Open-Label, Multicenter, Dose-Escalation and Expansion, Phase I Study to Evaluate Safety, Pharmacokinetics, And Anti-Tumor Activity of RO7300490, A Fibroblast Activation Protein-α (FAP) Targeted CD40 Agonist, as Single Agent or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

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

Intervention / Treatment
-----------------
* Drug: RO7300490
* Drug: Atezolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Life expectancy of >= 12 weeks. Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy. Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Agreement to provide protocol-specific biopsy material. Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<1. Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm. Exclusion Criteria: Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met. Active second invasive malignancy within two years prior to screening. Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start. Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug. Prior allogeneic bone marrow transplantation or prior solid organ transplantation. Active or history of autoimmune disease. Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation. Pregnancy, lactation or breastfeeding. Dementia or altered mental status that would prohibit informed consent. Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment. Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.

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 1: Dose Escalation (RO7300490 Monotherapy)<br>Participants will receive escalating doses of RO7300490 intravenously (IV) as a single agent for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. | Drug: RO7300490<br>* Participants will receive RO7300490, as described in the Arm Descriptions.<br>|
| Experimental: Part 2: Dose Escalation (RO7300490/atezolizumab combination therapy)<br>Participants will receive escalating doses of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label) for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. | Drug: RO7300490<br>* Participants will receive RO7300490, as described in the Arm Descriptions.<br>Drug: Atezolizumab<br>* Participants will receive Atezolizumab, as described in the Arm Descriptions.<br>|
| Experimental: Part 3: Dose Expansion (Disease-specific Expansion(s))<br>Participants with selected types of advanced and/or metastatic tumors will receive the maximum tolerated dose (MTD) or recommended dose for expansion (RDE) (determined from Parts 1 and 2) of RO7300490 in combination with a fixed dose of atezolizumab IV (as per label). Treatment will be administered for up to 24 months maximum or until progressive disease, unacceptable toxicities, death, or withdrawal of consent. | Drug: RO7300490<br>* Participants will receive RO7300490, as described in the Arm Descriptions.<br>Drug: Atezolizumab<br>* Participants will receive Atezolizumab, as described in the Arm Descriptions.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2) |  | Up to 36 months | 
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2) |  | Up to 36 months | 
| Objective Response Rate (ORR) (Part 3) |  | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3) |  | Up to 48 months | 
| Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3) |  | Up to 48 months | 
| Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3) |  | Up to 48 months | 
| Clearance (CL) of RO7300490 (Parts 1, 2 and 3) |  | Up to 48 months | 
| Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3) |  | Up to 48 months | 
| Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3) |  | Up to 48 months | 
| Objective Response Rate (ORR) (Parts 1 and 2) |  | Up to 48 months | 
| Disease Control Rate (DCR) (Parts 1, 2 and 3) |  | Up to 48 months | 
| Duration of Response (DOR) (Parts 1, 2 and 3) |  | Up to 48 months | 
| Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3) |  | Up to 48 months | 
| Percentage of Participants With Adverse Events (AEs) (Part 3) |  | Up to 48 months |