Golimumab and Apalutamide for the Treatment of Castration-Resistant Prostate Cancer, TRAMP Study

Inclusion Criteria:

• History of histologically diagnosed prostatic adenocarcinoma

• Participants must have progressed on no more than one novel hormonal therapy (NHT)by PSA or radiographic criteria (per Prostate Cancer Working Group 3 [PCWG3] orResponse Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) and a castrateserum testosterone level (i.e., ≤ 50 ng/dL). If progressive disease by radiographiccriteria, PSA must be ≥ 2ng/ml. PSA progression will be defined as at least twosuccessive PSA rises above the nadir, separated by ≥ 1 week, with the lastdetermination having a value of ≥ 2 ng/mL. NHTs include but are not limited toeither abiraterone, enzalutamide, darolutamide, or apalutamide. (Biosimilar orgeneric agents may be allowed at the discretion of the principal investigator [PI].)Note: prior NHT exposure that did not result in disease progression will not becounted as prior line, i.e., patient's that completed prior abiraterone course inthe localized setting, patients that changed NHT due to toxicity or financialtoxicity

• Participants must have previously progressed on a novel hormonal therapy (NHT) byPSA or radiographic criteria (per PCWG3 or RECIST v1.1). NHTs include but are notlimited to either abiraterone, enzalutamide, darolutamide, or apalutamide. (Biosimilar or generic agents may be allowed at the discretion of the principalinvestigator [PI].) Note: prior NHT exposure that did not result in diseaseprogression will not be counted as prior line, i.e., patient's that completed priorabiraterone course in the localized setting, patients that changed NHT due totoxicity or financial toxicity

• Participants may have received one prior line of taxane chemotherapy in any setting

• Participants must be >= 18 years of age prior to signing informed consent

• Eastern Cooperative Oncology Group (ECOG) performance status score =< 2

• Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 3months prior to randomization

• Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factorswithin 3 months prior to randomization

• Absolute neutrophil count >= 1.5 x 10^3/mL

• Serum albumin >= 3.0 g/dL

• Serum creatinine =< 1.5 mg/dL

• Serum potassium >= 3.5 mmol/L

• Serum total bilirubin < 1.5 x upper limit of normal (ULN) (Note: In subjects withGilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirectbilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkalinephosphatase =< 1.5 x ULN

• Agrees to use a condom (even men with vasectomies) and another effective method ofbirth control if he is having sex with a woman of childbearing potential or agreesto use a condom if he is having sex with a woman who is pregnant while on study drugand for 3 months following the last dose of study drug. Must also agree not todonate sperm during the study and for 3 months after receiving the last dose ofstudy drug

• Medications known to lower the seizure threshold (see list under prohibited meds)must be discontinued or substituted at least 4 weeks prior to study entry

• Have had no known recent close contact with a person with active tuberculosis (TB)or, if there has been such contact, will be referred to a physician specializing inTB to undergo additional evaluation

• Participants must sign an informed consent form (ICF) indicating that theyunderstand the purpose of, and procedures required for, the study and are willing toparticipate in the study

Exclusion Criteria:

• Subjects may not be receiving other investigational agents within 14 days prior toenrollment

• Subjects with predominant small cell or neuroendocrine variant prostate cancer onmost recent standard of care biopsy

• Evidence of serious and/or unstable pre-existing medical, psychiatric or othercondition that could interfere with patient safety

• Symptomatic central nervous system (CNS) metastases. Treated CNS metastases will beallowed if these are stable for at least 8 weeks prior to enrollment

• Uncontrolled or active infection, including:

• Hepatitis B infection (acute or chronic) as defined according to the AmericanSociety of Clinical Oncology guidelines, or hepatitis C infection (anti-hepatitis C virus [HCV] antibody positive and HCV-ribonucleic acid [RNA]quantitation positive)

• Recent serious infection (e.g., requiring IV antibiotics or hospitalizationwithin last two months)

• Herpes zoster infection within 2 months of screening

• History of active granulomatous infection, including histoplasmosis, orcoccidioidomycosis

• HIV (HIV antibody positive)

• Active or untreated latent tuberculosis

• History of infected joint prosthesis or received antibiotics for suspectedinfection of a joint prosthesis in the past five years, if that prosthesis hasnot been removed or replaced

• Less serious infections (e.g., acute upper respiratory tract infection, simpleurinary tract infection) need not be considered exclusionary at the discretionof the investigator

• Has impaired wound healing capacity defined as current skin/decubitus ulcers,chronic leg ulcers, known gastric ulcers, or unhealed incisions

• Major surgery within 2 weeks of the first dose, or will not have fully recoveredfrom surgery, or has surgery planned during the time the subject is expected toparticipate in the study or within 2 weeks after the last dose of study drugadministration (Note: subjects with planned surgical procedures to be conductedunder local anesthesia may participate)

• Co-administration of other TNF-alpha inhibitors or disease-modifying anti-rheumaticdrugs (DMARDS) for the treatment of rheumatoid arthritis or other rheumatologiccondition. (Note: prior exposure to TNF-alpha inhibitors is allowed fornon-rheumatologic disease (e.g., SARS-CoV-2) if washout period > 5 half-lives priorto study enrollment)

• Any other issue that would impair the ability of the subject to receive or toleratethe planned treatment at the investigational site, to understand informed consent orany condition for which, in the opinion of the investigator, participation would notbe in the best interest of the subject (e.g., compromise the well-being) or thatcould prevent, limit, or confound the protocol-specified assessments

• Presence of significant cardiovascular disease including New York Heart Association (NYHA) class II-IV heart failure, uncontrolled arrhythmia, myocardial infarction (MI) or stroke within 6 months

• History of autoimmune disorder, including multiple sclerosis or optic neuritis,lupus or lupus-like Syndrome

• Hypersensitivity to any biologics or known allergies or clinically significantreactions to murine, chimeric, or human proteins, monoclonal antibodies (mAbs), orantibody fragments

• Have a transplanted organ (with the exception of a corneal transplant performed > 3months prior to first administration of study drug)

• Currently has a malignancy or a history of malignancy within 3 years beforescreening (with the exception of prostate cancer, treated superficial bladdercancer, or a nonmelanoma skin cancer that has been adequately treated with noevidence of recurrence for at least 3 months prior to the administration of thefirst study intervention

• Immune deficiency syndrome (e.g., severe combined immunodeficiency syndrome [SCIDS],T cell deficiency syndromes, B cell deficiency syndromes, and chronic granulomatousdisease)

• Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.Patients must agree not to receive BCG vaccination during the study and within 16weeks after the last administration of study intervention

• Known allergies, hypersensitivity, or intolerance to apalutamide or its excipients

• Gastrointestinal disorder affecting absorption

• History of seizure or any condition that in the opinion of the investigator maypredispose to seizure or treatment with drugs known to lower the seizure thresholdwithin 4 weeks prior to starting treatment with apalutamide