A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer

• Inavolisib (Drug): Inavolisib will be administered orally as per the schedule specified in the protocol.
• Enzalutamide (Drug): Enzalutamide will be administered orally as per the schedule specified in the protocol.
• Abiraterone (Drug): Abiraterone will be administered orally as per the schedule specified in the protocol.
• Docetaxel (Drug): Docetaxel will be administered intravenously as per the schedule specified in the protocol.

Primary outcomes

• Radiographic Progression-free Survival (rPFS) [Up to approximately 5 years]

Secondary outcomes

• Percentage of Participants with Confirmed Composite Response Rate (RR) [Up to approximately 5 years]
• Percentage of Participants with Confirmed Prostate-Specific Antigen 90 (PSA90) [Up to approximately 5 years]
• Percentage of Participants with Confirmed Prostate-Specific Antigen 50 (PSA50) [Up to approximately 5 years]
• Objective Response Rate (ORR) [Up to approximately 5 years]
• Duration of Response (DOR) [Up to approximately 5 years]
• Overall Survival (OS) [Up to approximately 5 years]
• Percentage of Participants With Adverse Events (AEs) [Up to approximately 5 years]

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without small-cell or neuroendocrine features
* Progressive metastatic CRPC, defined as any of the following: PSA progression, defined by a minimum of two rising PSA values from three consecutive assessments with an interval of at least 7 days between assessments and with a minimal starting value of PSA >=1 ng/mL; The most recent qualifying PSA value must be determined within 14 days of enrollment; Soft tissue disease progression, defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); Bone disease progression, defined by PCWG3 criteria, with two or more new metastatic bone lesions on a whole-body radionuclide bone scan
* Treatment with at least one, but no more than one, prior second-generation ARPi (abiraterone, apalutamide, enzalutamide, darolutamide) for at least 12 weeks for HSPC or CRPC
* Availability of a tumor tissue specimen that is suitable (e.g., adequate quality and quantity) for use in determining biomarker status
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Fasting glucose <126 mg/dL and HbA1c < 6%

Exclusion Criteria:

* Presence of liver metastasis
* Prior treatment with any phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or with any agent with a mechanism of action of inhibiting the PI3K/AKT/mTOR pathway
* Type 1 or Type 2 diabetes mellitus
* Prior treatment for mCRPC with cytotoxic chemotherapy or novel hormonal treatments (e.g., androgen receptor degraders, CYP11 inhibitors), with the following treatments permitted: Prior docetaxel in mHSPC, providing no evidence of disease progression occurred during treatment or within 6 months of treatment completion; Prior docetaxel in the adjuvant or neoadjuvant setting providing no evidence of disease progression occurred during treatment or within 12 months of treatment completion; Prior treatment with sipuleucel-T, with the last dose administered >28 days prior to start of treatment; Prior PARPi therapy, as per local prescribing information, with the last dose administered >14 days prior to start of treatment; One prior RLT or radiotherapeutic agent (e.g., PSMA-targeted RLT, Radium 223) with the last dose administered >8 weeks prior to start of treatment
* Other concurrent anti-cancer therapy except for androgen deprivation therapy
* Treatment with strong CYP2C8 inhibitors, strong or moderate CYP2C8 inducers, or strong CYP3A4 inducers within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment
* Transfusion of any blood product for the sole purpose of making a potential participant eligible for study inclusion or within 28 days of enrollment

• Clinical Trials, Study director, Hoffmann-La Roche

NIH grants: 2025