Abiraterone Acetate in Combination With Tildrakizumab

Inclusion Criteria: 1. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up. 2. Age 18 or above. 3. Histologically or cytologically proven adenocarcinoma of the prostate. 4. Metastatic castration resistant prostate cancer 5. Documented prostate cancer progression as assessed by the investigator with RECIST (v1.1) and PCWG3 criteria with at least one of the following criteria: 1. Progression of soft tissue/visceral disease by RECIST (v1.1) and/or, 2. Progression of bone disease by PCWG3 bone scan criteria and/or, 3. Progression of PSA by PCWG3 PSA criteria and/or, 4. Clinical progression with worsening pain and need for palliative radiotherapy for bone metastases. 6. Patients that have progressed after either enzalutamide or abiraterone treatment (having received a minimum of 12-weeks of enzalutamide or abiraterone). 7. Ongoing androgen deprivation with a luteinizing hormone releasing hormone analogue (unless the patient is surgically castrated) maintaining serum testosterone of less than 50 ng/dL (less than 2.0 nM) is mandatory. 8. Life expectancy of at least 12-weeks. 9. World Health Organisation (WHO) performance status of 0-2 10. Able to swallow the study drug. 11. Archival tissue must be available for research analysis. 12. Patients must have disease that is amenable to biopsy and must be willing to undergo tumour biopsies. 13. Haematological and biochemical indices within the required ranges in protocol. These measurements must be performed within two weeks prior to the patient's first dose of any investigational medicinal products (IMP). Exclusion Criteria: 1. Patients with predominantly small cell or neuroendocrine differentiated prostate cancer are not eligible. 2. Prior therapy, including major surgery, chemotherapy, radium-223, or other anti-cancer therapy within 4-weeks prior to IMP administration. Patients who were receiving abiraterone acetate (Zytiga® or Yonsa™) immediately prior to trial entry will not need to undergo a washout period. The use of bisphosphonates or RANK ligand inhibitors, provided the patient has been on a stable dose without any dose adjustment for at least 30 days prior to combination Cycle 1 Day 1, in patients with known osteopenia or osteoporosis or bone metastases is permitted. A single fraction of palliative radiation is permitted if at least 14-days before starting trial treatment. 3. Prior hormonal treatment exclusions as follows: * prior flutamide treatment during previous four-weeks N.B. Patients whose PSA did not decline in response to antiandrogens given as a second line or later intervention will only require a 14-day washout; * prior bicalutamide (Casodex) and nilutimide (Nilandron) treatment during previous six-weeks; * prior progesterone, medroxyprogesterone, progestins, cyproterone acetate, tamoxifen, and 5-alpha reductase inhibitors during previous two-weeks (14-days). 4. Live vaccine within 4 weeks of starting trial treatment and up to 17 weeks from the last dose of Tildrakizumab. 5. Prior limited field radiotherapy within the previous two weeks (14-days), or wide field radiotherapy within the previous four weeks of trial entry. 6. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within four weeks prior to IMP administration. 7. Any toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to NCI-CTCAE v5.0 Grade ≤1 with the exception of chemotherapy induced alopecia and Grade 2 peripheral neuropathy. 8. Clinical evidence of hyperaldosteronism or hypopituitarism. 9. Use of drugs that are known strong CYP3A4 inducers and CYP2D6 substrates with a narrow therapeutic index (please refer to http://medicine.iupui.edu/clinpharm/ddis/table.aspx). Seville orange or grapefruit products, and any herbal medications should be avoided for four weeks prior to starting trial treatment. 10. Malabsorption syndrome or other condition that would interfere with enteral absorption of the study drugs. 11. Known intracerebral metastases 12. Any of the following cardiac criteria: 1. QT interval \> 470 msec. 2. Clinically important abnormalities including rhythm, conduction or ECG changes (left bundle branch block, third degree heart block). 3. Factors predisposing to QT prolongation including congenital long QT syndrome; family history of prolonged QT syndrome, unexplained sudden death (under 40); concomitant medications known to prolong QT interval. 4. Coronary artery bypass, angioplasty, vascular stent, myocardial infarction, angina or congestive heart failure (NYHA ≥ grade 2) in the last 6 months (see the NYHA scale). 13. Uncontrolled hypotension (systolic blood pressure \< 90mmHg and or diastolic blood pressure \< 50 mmHg). 14. Uncontrolled hypertension on optimal medication (systolic blood pressure \>180, diastolic blood pressure \> 100). 15. Patients with known history of adrenal insufficiency or mineralocorticoid excess. 16. Patients with a significant history of liver disease (Child-Pugh B or C, viral or other hepatitis, current alcohol abuse or cirrhosis). 17. Known history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 18. At high medical risk because of non-malignant systemic disease including active infection, latent or active TB. 19. Known history of tuberculosis. 20. Poorly controlled diabetes with HbA1C \> 7.5%. 21. Malignancy other than prostate cancer within three-years of trial entry with the exception of adequately treated basal cell carcinoma. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy must have no evidence of that disease for at least-three years and be deemed at negligible risk for recurrence, are deemed eligible. 22. Immunocompromised patients including patients who have previously received organ transplants or are on long-term immunosuppression (e.g. corticosteroids of \> 10 mg daily equivalent of prednisolone). 23. Active or uncontrolled autoimmune disease requiring corticosteroid therapy or other forms of systemic immunosuppression. 24. Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect interpretation of the results or renders the patients at high risk from treatment complications e.g. patients with a hypersensitivity to tildrakizumab, abiraterone, prednisolone, or any of the drug excipients. 25. Patients with female partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception \[condom plus spermicide\] or to sexual abstinence effective from the first administration of any of the study drugs throughout the trial and for six months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate. NB. Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the participants. Periodic abstinence (e.g., calendar, ovulation, sympathothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception 26. Prior bone marrow transplant. 27. Extensive radiotherapy to greater than 25% of bone marrow within 8 weeks. 28. Any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial. 29. Symptoms of COVID-19 and/or documented COVID-19 infection