Phase II Study of Inavolisib and Enzalutamide Versus Physician's Choice of ARPI or Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer
- Trial ID
- 2025-521327-67-00
- Protocol
- CO45813
- Sponsor
- F. Hoffmann-La Roche AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of inavolisib combined with enzalutamide compared to an investigator's choice of androgen receptor pathway inhibitor switch or docetaxel, specifically regarding radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer. 5
Secondary objectives include the assessment of:
- Confirmed composite response rate
- Prostate-specific antigen 90, prostate-specific antigen 50, objective response rate, duration of response, and overall survival
- Safety, measured by the incidence and severity of adverse events according to NCI CTCAE v5.0, changes in vital signs, and changes in clinical laboratory test results. 4
Participants
This clinical trial involves 68 male participants diagnosed with metastatic castration-resistant prostate cancer. The study population consists of individuals with histologically or cytologically confirmed adenocarcinoma of the prostate, excluding those with small-cell or neuroendocrine features. Eligible participants must demonstrate disease progression through prostate-specific antigen elevation, soft tissue progression according to RECIST v1.1, or bone disease progression based on PCWG3 criteria. Selection requires a history of treatment with exactly one prior second-generation androgen receptor pathway inhibitor. Additionally, participants must meet specific metabolic requirements, including a fasting glucose level of ≤ 100 mg/dL and an HbA1c level of < 5.7%. The availability of a suitable tumor tissue specimen for biomarker determination is also required for enrollment.
Plans and Procedures
This Phase II, randomized, multicenter, open-label study evaluates the efficacy and safety of a combination of inavolisib and enzalutamide compared to a physician's choice of an androgen receptor pathway inhibitor or docetaxel in patients with metastatic castration-resistant prostate cancer. The primary endpoint is radiographic progression-free survival. Secondary endpoints include overall survival, objective response rate, and the incidence of adverse events. The methodology involves comparing the test combination against a control arm consisting of either an abiraterone switch or docetaxel. The study is estimated to occur between March 2026 and September 2028.
Treatment
Inavolisib is administered as a film-coated tablet via the oral route. This experimental medication is part of a combination therapy regimen.
Enzalutamide is administered orally at a dosage of 160 mg. This substance is utilized as part of the experimental combination treatment.
Docetaxel is utilized as a comparator treatment and is administered via intravenous use at a dose of 75 mg/m².
Abiraterone is employed as a comparator treatment and is administered at a dose of 1000 mg via the oral route.
Efficacy
The primary efficacy endpoint for this study in patients with metastatic castration-resistant prostate cancer is radiographic progression-free survival (rPFS). Secondary efficacy parameters include the confirmed composite response rate (RR), confirmed prostate-specific antigen 90 (PSA90), confirmed prostate-specific antigen 50 (PSA50), objective response rate (ORR), duration of response (DOR), and overall survival (OS).
Inclusion and Exclusion Criteria
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 hormone-sensitive prostate cancer (HSPC) or castrate-resistant prostate cancer (CRPC)
- Prior ARPi must have been discontinued as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate or darolutamide within 2 weeks prior to start of treatment. In addition, no evidence of radiographic disease progression should have occurred during prior enzalutamide, apalutamide or darolutamide treatment or intolerable toxicity to enzalutamide. First generation androgen receptor inhibitor therapy (e.g., bicalutamide) is allowed and is not considered to be prior ARPi therapy. It must be discontinued > 6 weeks prior to start of treatment.
- Availability of a tumor tissue specimen that is suitable (e.g., adequate quality and quantity) for use in determining biomarker status
- Fasting glucose </= 100 mg/dL and HbA1c < 5.7%
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
- Other concurrent anti-cancer 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 13 Mar 2026 | 9 |
 Germany | Recruiting | 13 Mar 2026 | 7 |
 Italy | Recruiting | 13 Mar 2026 | 8 |
 Spain | Recruiting | 13 Mar 2026 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ABIRATERONE | Comparator | — | ORAL | 1000 | 60 | SUB07361MIG |
DOCETAXEL | Comparator | — | INTRAVENOUS USE | 75 | 210 | SUB12492MIG |
ENZALUTAMIDE | Test | — | ORAL | 160 | 60 | SUB77412 |
INAVOLISIB | Test | FILM-COATED TABLET | ORAL | 0 | 1 | PRD9793811 |
ENZALUTAMIDE | Test | — | ORAL | 160 | 60 | SUB77412 |
INAVOLISIB | Test | FILM-COATED TABLET | ORAL | 0 | 1 | PRD9793132 |