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

This phase II trial tests how well golimumab and apalutamide work in treating patients with castration resistant prostate cancer. Golimumab is in a class of medications called tumor necrosis factor (TNF) inhibitors. It works by blocking the action of TNF, a substance in the body that causes inflammation. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving golimumab and apalutamide may work better in treating patients with castration-resistant prostate cancer.

OUTLINE:

Patients receive golimumab subcutaneously (SC) every 4 weeks for 6 doses and apalutamide orally (PO) daily. Treatment with apalutamide continues in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy at baseline and during cycle 4. Patients also undergo computed tomography (CT) scans or magnetic resonance imaging (MRI), prostate-specific membrane antigen (PSMA) positron emission tomography (PET), bone scan, and collection of blood samples throughout the study.

After completion of study treatment, patients are followed every 3 months.

Eligibility Criteria:
Inclusion Criteria:

* History of histologically diagnosed prostatic adenocarcinoma
* Participants must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising prostate specific antigen (PSA) or radiographic progression (per Prostate Cancer Working Group 3 \[PCWG3\] or Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1) and a castrate serum testosterone level (i.e., =\< 50 ng/dL)
* Participants must have previously progressed on a novel hormonal therapy (NHT) by PSA or radiographic criteria (per PCWG3 or RECIST v1.1). NHTs include but are not limited to either abiraterone, enzalutamide, darolutamide, or apalutamide. (Biosimilar or generic 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 be counted as prior line, i.e., patient's that completed prior abiraterone course in the localized setting, patients that changed NHT due to toxicity or financial toxicity
* Participants must have actively progressing disease at the time of enrollment by either PSA or radiographic criteria (if progressive disease by radiographic progression, PSA must be ≥ 2ng/ml). PSA progression will be defined as at least two successive PSA rises above the nadir, separated by ≥ 1 week, with the last determination having a value of ≥ 2 ng/mL. Radiographic progression will be per PCWG3 or RECIST v1.1 criteria
* 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 3 months prior to randomization
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 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 with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject may be eligible)
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase =\< 1.5 x ULN
* Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study 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 no signs or symptoms suggestive of active tuberculosis (TB) upon medical history and/or physical examination
* Have had no known recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation
* Within 42 days before the first administration of study intervention, have a negative QuantiFERON-TB test result
* Have a chest radiograph (both posterior-anterior and lateral views, or per country regulations where applicable), taken within 12 weeks before the first administration of study intervention and read by a radiologist or qualified pulmonologist, with no evidence of current, active TB or old, inactive TB. A chest computed tomography scan is also acceptable if already available or obtained outside of the study protocol
* Participants must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study

Exclusion Criteria:

* Subjects may not be receiving other investigational agents within 14 days prior to enrollment
* Subjects with predominant small cell or neuroendocrine variant prostate cancer on most recent standard of care biopsy
* Symptomatic central nervous system (CNS) metastases. Treated CNS metastases will be allowed if these are stable for at least 8 weeks prior to enrollment
* Hepatitis B infection (acute and chronic) as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status. Hepatitis C (anti-hepatitis C virus \[HCV\] antibody positive or HCV-ribonucleic acid \[RNA\] quantitation positive) or known to have a history of hepatitis C. If positive, further testing of quantitative levels to rule out positivity is required
* Has impaired wound healing capacity defined as 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 recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate)
* Co-administration of other TNF-alpha inhibitors or disease-modifying anti-rheumatic drugs (DMARDS) for the treatment of rheumatoid arthritis or other rheumatologic condition. (Note: prior exposure to TNF-alpha inhibitors is allowed for non-rheumatologic disease (e.g., SARS-CoV-2) if washout period \> 5 half-lives prior to study enrollment)
* Uncontrolled or concurrent illness including within the past 6 months, but not limited to, ongoing or active infection, history or ongoing chronic or recurrent infectious diseases, or any immune deficiency syndromes, severe or unstable angina, myocardial infarction, congestive heart failure (asymptomatic or symptomatic), uncontrolled hypertension, clinically significant arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease, or psychiatric illness/social situations that would limit compliance with study requirements
* Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
* History of active or latent TB prior to screening or evidence of active or latent TB during screening
* History or ongoing chronic or recurrent infectious diseases, or any immune deficiency syndromes
* Concomitant diagnosis or history of congestive heart failure (CHF), including medically controlled asymptomatic CHF
* Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable angina, rapid atrial fibrillation, or transient ischemic attack) in the last 3 months prior to screening or a cardiac hospitalization within the last 3 months prior to screening
* History of a demyelinating disorder such as multiple sclerosis or optic neuritis
* Lupus or Lupus-like syndrome
* Hypersensitivity to any biologics or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies (mAbs), or antibody fragments
* Have a transplanted organ (with the exception of a corneal transplant performed \> 3 months prior to first administration of study drug)
* Currently has a malignancy or a history of malignancy within 5 years before screening (with the exception of prostate cancer or a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months prior to the administration of the first study intervention
* Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance; or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly
* Has or has had a herpes zoster infection within 2 months before screening
* Have had a serious infection (e.g., hepatitis, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with parenteral antibiotics for an infection within 2 months prior to first administration of study drug. Less serious infections (e.g., acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator
* Immune deficiency syndrome (e.g., severe combined immunodeficiency syndrome \[SCIDS\], T cell deficiency syndromes, B cell deficiency syndromes, and chronic granulomatous disease)
* Are known to be infected with HIV (HIV antibody positive)
* Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening

  * Note: Patients must agree not to receive a Bacillus Calmette-Guerin (BCG) vaccination during the study, and within 16 weeks after the last administration of study intervention
* Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, pneumocystis jirovecii, aspergillosis)
* Has a history of active granulomatous infection, including histoplasmosis, or coccidioidomycosis, before screening
* Have signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, vascular, GI, rheumatologic, neurologic, psychiatric, or cerebral diseases
* Suicidal ideation
* Has a history of an infected joint prosthesis or has ever received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced
* Known allergies, hypersensitivity, or intolerance to apalutamide or its excipients
* Uncontrolled hypertension
* Gastrointestinal disorder affecting absorption
* Seizure or known condition that may pre-dispose to seizure (e.g., prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy)
* History of seizure or any condition that in the opinion of the investigator may predispose to seizure or treatment with drugs known to lower the seizure threshold within 4 weeks prior to starting treatment with apalutamide