A Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7656594 In Participants With Advanced or Metastatic Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or metastatic prostate cancer. It will also identify recommended doses and regimens for RO7656594 for subsequent studies.

Official Title
-----------------
A Phase 1, Open-Label, Multicenter, Dose-Escalation and Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7656594 in Patients With Advanced or Metastatic Prostate Cancer

Conditions
-----------------
Advanced Prostate Cancer, Metastatic Prostate Cancer

Intervention / Treatment
-----------------
* Drug: RO7656594


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Metastatic prostate adenocarcinoma without small-cell carcinoma or neuroendocrine features. Prior therapy with ≥1 second-generation androgen receptor (AR)-targeted therapy (e.g., abiraterone, enzalutamide, apalutamide, darolutamide). Prior therapy with ≥1 taxane regimen or are considered ineligible for treatment with a taxane regimen or have refused treatment with a taxane regimen. Key Exclusion Criteria: Treatment with any approved systemic anti-cancer therapy within 14 days or 5 drug elimination half-lives (whichever is longer, not to exceed 28 days) prior to the first study treatment. Treatment with any investigational agent within 28 days prior to the first study treatment. Treatment with any previous AR protein degrader. Untreated central nervous system (CNS) metastases or leptomeningeal disease. Note: Other protocol specified inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

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: Stage 1: Dose Escalation<br>Participants will receive RO7656594 administered at a specified dose on specific days in each 28-day cycle. The dose will be increased in successive cohorts until a study-specific threshold is reached. | Drug: RO7656594<br>* RO7656594 will be administered orally at specified dose on specified days.<br>* Other names: GDC-2992;|
| Experimental: Stage 2: Expansion<br>Participants will receive RO7656594 at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD). | Drug: RO7656594<br>* RO7656594 will be administered orally at specified dose on specified days.<br>* Other names: GDC-2992;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | From Cycle 1 Day 1 until 28 days after the final dose (Up to approximately 24 months) (1 cycle= 28 days) | 
| Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs) |  | Days 1-28 of Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Area Under Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Area Under Concentration-Time Curve From Time Zero to End of the Dosing Interval (AUC0-T) of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Maximum Plasma Concentration Observed (Cmax) of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Time to Maximum Plasma Concentration Observed (tmax) of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Minimum Plasma Concentration Observed (Cmin) of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Total Apparent Clearance of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Volume of Distribution at Steady State of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Half-life of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Accumulation Ratio at Steady-State of RO7656594 |  | Multiple timepoints from Cycle 1 Day 1 up to approximately 12 months (1 cycle= 28 days) | 
| Prostate-Specific Antigen-30% (PSA30) Response Rate of RO7656594 |  | From Cycle 1 Day 1 until 28 days after the final dose (Up to approximately 24 months) (1 cycle= 28 days) | 
| Prostate-Specific Antigen-50% (PSA50) Response Rate of RO7656594 |  | From Cycle 1 Day 1 until 28 days after the final dose (Up to approximately 24 months) (1 cycle= 28 days) | 

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