Prostate Adenocarcinoma, Prostate Cancer, Localized Prostate Cancer
Conditions
Keywords
Neoadjuvant therapy
Brief summary
This phase II trial studies how well atezolizumab works alone or in combination with etrumadenant or tocilizumab in treating men with localized prostate cancer before radical prostatectomy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Androgens can cause the growth of prostate cancer cells. IL-6 is expressed by prostate cancer and within the tumor microenvironment and shown to enhance prostate cancer and disease progression. Treatment with an anti-IL-6 antibody such as tocilizumab may inhibit cancer progression. Giving atezolizumab in combination with etrumadenant or tocilizumab may work better in treating prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine the impact of atezolizumab-based combination therapy on the composition and function of tumor-infiltrating immune cells (TIICS). SECONDARY OBJECTIVES: I. To determine the safety and tolerability of atezolizumab-based combination therapy in localized prostate cancer (PC). II. To determine the clinical efficacy of atezolizumab-based combination therapy in localized PC. EXPLORATORY OBJECTIVES: I. To characterize changes in the frequency and number of circulating immune cells following atezolizumab-based combination therapy in localized PC. II. To determine the impact of atezolizumab-based combination therapy on the composition and phenotype of the tumor microenvironment. III. To determine the impact of atezolizumab-based combination therapy on the circulating and intratumoral T cell repertoire. IV. To explore the role of novel imaging modalities to understand the immunologic and clinical impact to immunotherapeutic approaches in localized PC. V. To characterize changes in the gut microbiome associated with each therapeutic combination. OUTLINE: Participants are assigned to 1 of 3 cohorts. COHORT A: Participants receive one cycle of atezolizumab intravenously (IV) over 30-60 minutes on day 1 of a 14 day cycle prior to radical prostatectomy (RP). COHORT B: Participants will receive 1 cycle of neoadjuvant atezolizumab and etrumadenant (AB928) prior to RP; atezolizumab will be administered in an identical fashion as Cohort A. Etrumadenant will be administered at a dose of 150 mg once daily, until 48 hours prior to RP. COHORT C: Participants will receive 1 cycle of neoadjuvant atezolizumab and tocilizumab prior to RP; atezolizumab will be administered in an identical fashion as Cohort A. Etrumadenant will be administered at a dose of 6mg/kg. Two more groups consisting of treatment with atezolizumab in combination with other drugs may be added in the future. RP will occur 21 days (+/- 7 days) following treatments on Cycle 1 Day 1. No further study therapy will be administered following RP. Following RP, participants will be followed at 6 weeks, 3 months, 6 months, and 12 months (from date of RP), or until disease progression, whichever occurs sooner
Interventions
Sponsors
Genentech, Inc.
Arcus Biosciences, Inc.
David Oh
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the prostate. a. Subjects with small cell or neuroendocrine PC are not eligible. 2. Eligible for radical prostatectomy as determined by urologic oncology surgeon, and subject consents to proceeding with radical prostatectomy. a. Deemed by urologic oncology surgeon to be appropriate for a window-of-opportunitystudy. 3. Only patients with high-risk disease are eligible for the safety lead-in for each cohort. Patients with intermediate-risk disease will be included after interim analyses is complete for the corresponding cohort and the PI has determined that it is safe to do so. 4. Availability of a representative tumor specimen that is suitable for the planned study analyses, as determined by the Principal Investigator. 1. A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study treatment. If only 10-14 slides are available, the patient may still be eligible for the study, after Principal Investigator approval has been obtained. 2. If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Refer to Section 6.3 for additional information on tumor specimens collected at screening. 5. Subjects have not received any prior systemic or locally directed therapy for PC (see
Exclusion criteria
). 6. Age \>= 18 years 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 8. Requirements for organ and marrow function: * Hemoglobin \>= 9 g/dL * \- Participants must not have been transfused within 2 weeks prior to screening to meet this criterion * Absolute neutrophil count \>= 1,500/microliter (uL) without granulocyte colonystimulating factor support * Absolute lymphocyte count \>= 500/uL * Platelets \>= 100,000/uL without transfusion * Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (known Gilbert disease: \< 3 x ULN) * Alkaline phosphatase \< 2 x institutional ULN * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =\< 2 x institutional ULN * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2 x institutional ULN * International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \< 1.5 x institutional ULN for subjects not receiving therapeutic anticoagulation * Creatinine clearance \>= 30 mL/min (calculated using the Cockcroft-Gault formula) * Serum creatinine \<=1.6 mg/dL (141 μmol/L) in female patients and ≤1.9 mg/dL (168 μmol/L) in male patients . Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are \>30 9. Testosterone level \> 150 ng/dL. 10. Contraception: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm as defined below: 1. With female partners of childbearing potential: men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 4 months after the last dose of study treatment. Men must refrain from donating sperm during the same period 2. With pregnant female partners: men must remain abstinent or use a condom during the treatment period and for 4 months after the last dose of study treatment to avoid exposing the embryo 3. Abstinence: the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception 11. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen \> 3 months. 12. Ability to understand a written informed consent document, and the willingness to sign it. 13. Ability to comply with the study protocol, in the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects who demonstrate a positive response to neoadjuvant atezolizumab and atezolizumab-based combination therapy for each Cohort of the study | Up to 12 months | A positive response is defined as a ≥40% increase in the number of infiltrating cluster of differentiation 3 (CD3) + T cells between the pre-treatment biopsy at baseline and the post-treatment RP specimen. Thus, a negative response is a \<40% increase. The primary endpoint will include all enrolled subjects who receive at least 1 dose of study treatment and undergo RP. Analysis of the primary endpoint will be performed for each cohort independently |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-related of adverse events | Up to 12 months | The number of treatment-related adverse events will be reported and classified per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Sum of Pathologic complete response (pCR) and Minimal residual disease (MRD) rate | Up to 12 months | Defined as defined as the absence of tumor on the gross specimen.Will be reported following standard pathologic review of the radical prostatectomy (RP) specimen. These will be reported in sum \[pCR+ MRD) rate\] and independently. |
| Rate of Pathologic complete response (pCR) rate | Up to 12 months | Defined as defined as the absence of tumor on the gross specimen.Will be reported following standard pathologic review of the radical prostatectomy (RP) specimen. These will be reported in sum \[pCR+ minimal residual disease (MRD) rate\] and independently. |
| Rate of Minimal residual disease (MRD) | Up to 12 months | Defined as the sum of the cross-sectional diameter of residual tumors =\< 0.5 cm. Will be reported following standard pathologic review of the RP specimen. These will be reported in sum (pCR+MRD rate) and independently. |
| Prostate specific antigen (PSA) response | Up to 12 months | Defined as \>= 50% decline in PSA. The PSA response proportion will be reported for each cohort. |
Countries
United States
Contacts
Primary ContactUCSF HDFCCC Cancer Immunotherapy Program (CIP)
Outcome results
None listed