Combining immune therapy and radiation for prostate cancer treatment

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

This study is testing a new treatment that combines immune therapy drugs with targeted radiation to see if it helps men with a specific type of prostate cancer live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years to 99 Years
• Sex: Male
• Sponsor: Columbia University (Academic / other)
• Drugs / interventions: radiation, zimberelimab, Immunotherapy
• Locations: 1 site (New York, New York)
• Trial ID: NCT05915442 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of a combination of drugs, including zimberelimab, etrumadenant, and quemliclustat, alongside metastasis-directed radiation therapy in men with hormone-sensitive oligometastatic prostate cancer. The goal is to inhibit the adenosine signaling pathway and enhance immune response to improve local control and progression-free survival. By utilizing advanced imaging technologies, the study aims to better target and treat patients with limited metastatic disease. The combination therapy is hypothesized to mitigate immunosuppressive changes in the tumor microenvironment compared to radiation therapy alone.

Who should consider this trial

Good fit: Ideal candidates include men aged 18 and older with hormone-sensitive oligometastatic prostate cancer and specific PSA levels.

Not a fit: Patients with advanced metastatic disease beyond the oligometastatic stage or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with oligometastatic prostate cancer.

How similar studies have performed: Other studies have shown promise in combining immune checkpoint inhibitors with radiation therapy, suggesting potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Patient must have histologically confirmed adenocarcinoma of the prostate.
2. Patient's primary prostate cancer tumor treated with surgery and/or radiation (+/- ADT).
3. Patients must have one to three asymptomatic metastatic tumors of the bone or soft tissue that developed in the preceding 6 months that are \< 5cm or \< 250 cm3.
4. Prostate-specific antigen (PSA) \> 0.5 ng/mL but \< 50ng/ml
5. PSA doubling time (PSADT) \< 15 months (using all available PSA values from time of relapse)
6. Testosterone \> 125 ng/mL
7. Age ≥18 years.
8. Patient must have life expectancy \> 12 months.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
10. Normal organ and marrow function as defined below:

    * leukocytes ≥3,000/mcL
    * absolute neutrophil count ≥1,500/mcL
    * platelets ≥100,000/mcL
    * total bilirubin within normal institutional limits
    * aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase (SGOT))/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase (SGPT) ) ≤2.5 × institutional upper limit of normal creatinine, within normal institutional limits
11. Male participants with female partners of childbearing potential are required to use highly effective contraceptive measures which include condom use. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. A female partner of is considered a woman of childbearing potential (WOCBP) following menarche and until becoming postmenopausal unless permanently sterile.

    * Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
    * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

    Highly effective contraceptive measures include:
    * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
    * Progestogen only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
    * Intrauterine device
    * Intrauterine hormone-releasing system
    * Surgical sterilization
    * The male participant is vasectomized (with documented medical confirmation of surgical success) and is the sole sexual partner of the WOCBP participant
    * Female partner of the male participant has undergone bilateral tubal ligation
    * Complete sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
12. Male participants should refrain from donating sperm for 180 days after the last dose of the study drugs.
13. Patient must have the ability to understand and the willingness to sign written informed consent.

Exclusion Criteria:

1. Patient may not have had prior systemic therapy, with the exception of androgen deprivation therapy (ADT) associated with treatment of the primary prostate tumor or with salvage radiation therapy. The ADT could not exceed 3-years in duration and must have occurred greater than 6 months before time of enrollment.
2. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
3. Spinal cord compression or impending spinal cord compression.
4. Pulmonary and/or liver metastases \> 1.0cm in largest dimension.
5. History of malignancy other than prostate cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as nonmelanoma skin carcinoma or ductal carcinoma in situ.
6. Use of other investigational agents or treatment protocol.
7. Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment with the exception of patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
8. Inability to swallow medications.
9. Malabsorption condition that would alter the absorption of orally administered medications.
10. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment.
11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
12. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
13. Positive total hepatitis B core antibody (HBcAb) test at screening. Patients can be eligible if positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV test will be performed only for participants who have a positive total HBcAb test. Due to safety concerns related to viral activation, development of a secondary malignancy, as well as the potential for increased treatment-related toxicity, eligible participants must not have evidence of chronic viral infection at screening.
14. Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:

    1. Oral treatment with strong inhibitors of breast cancer resistance protein (BCRP) (e.g., cyclosporin A, eltrombopag) or BRCP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.
    2. Oral treatment with strong inhibitors of P-glycoprotein (P-gp) substrates (e.g., itraconazole, quinidine, verapamil, dronedarone, ranolazine) or P-gp with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.
    3. Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
    4. Treatment with known strong UDP-glucuronosyltransferases (UGTs) of UGT1A1, 1A4, 1A9 and 2B4 inhibitors (e.g., atazanavir) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
    5. Treatment with known sensitive substrates of BSEP within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
    6. Treatment with known sensitive substrates of OCT2 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
    7. Treatment with known sensitive substrates of MATE1 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
15. Immunosuppression (e.g., solid organ transplant on immunosuppression).
16. No known HIV, or active with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV).
17. Active autoimmune disease.
18. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
19. Inability to lie flat to tolerate computed tomography (CT) simulation study and oligometastasis-directed stereotactic body radiotherapy (SBRT).
20. Use of any live vaccines against infectious diseases within 28 days of first dose of investigational products.
21. Refusal to sign informed consent.

Where this trial is running

New York, New York

• Columbia University Irving Medical Center / NewYork-Presbyterian Hospital — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Catherine S. Spina, MD, PhD — Columbia University
• Study coordinator: Catherine S. Spina, MD, PhD

Conditions Oligometastatic Prostate Cancer; Adenosine Signaling; AB680; AB928; AB122; Quemliclustatm; Etrumadenant; Zimberelimab