TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors

Inclusion Criteria:

* Histologically or cytologically confirmed metastatic solid tumor, including but not limited to pancreatic adenocarcinoma, breast cancer, melanoma, renal cell carcinoma (RCC), colorectal adenocarcinoma, non-small cell lung cancer, and others approved by the principal investigator
* Persistent, recurrent or progressive disease following at least one prior line of systemic therapy and there is no available therapy likely to improve survival
* Measurable disease with \>= 1 target lesion
* White blood cells (WBC) \>= 4200/mm\^3
* Absolute neutrophil count (ANC) \>= 1400/mm\^3
* Platelets (PLT) \>= 100,000/mm\^3
* Lymphocytes \>= 700/mm\^3
* Hemoglobin \>= 10 g/dL
* Total bilirubin =\< 1.5 X upper limit of normal (ULN) unless history of Gilbert's syndrome documented prior to first-line treatment of cancer and other liver function tests are within normal limits
* Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.2 x ULN unless on anticoagulation medication with stable dosing for at least one month; in addition, patient must be able to stop taking medication for up to a week in order to have percutaneous biopsies of tumor tissue performed
* Aspartate transaminase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN (=\< 5 x ULN for patients with liver involvement)
* Creatinine =\< ULN or a calculated creatinine clearance of \>= 45 ml/min if creatinine is greater than the ULN
* Alkaline phosphatase =\< 3 x ULN (=\< 5 x ULN if liver or bone involvement)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Willing and able to provide informed written consent
* Willing and able to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study); Note: During the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing and able to return to the consenting institution for follow-up
* Estimated life expectancy \>= 84 days (3 months)
* Willing and able to provide samples for correlative research purposes
* If female of child-bearing potential, have a negative pregnancy test =\< 14 days prior to registration
* If fertile male or female of child-bearing potential, agree to consistently use a highly effective method of birth control (including birth control pills, barrier device, or intrauterine device) from the time of consent through 4 months following the last dose of study drug

Exclusion Criteria:

* Is pregnant, breastfeeding, or planning a pregnancy
* Known standard therapy for the patient's disease that is potentially curative
* Treatment with any systemic anticancer treatment or an investigational agent within 4 weeks and any radiation within 2 weeks of registration
* 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 subject safety or compliance with study requirements
* Active autoimmune disease, defined as any autoimmune condition currently requiring therapy (e.g., systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis)
* History of other invasive malignancy, with the exception of non-melanoma skin cancer and well-excised cervical carcinoma in situ, =\< 3 years prior to enrollment unless assessed by the principal investigator as unlikely to compromise subject safety or to interfere with the study's objectives
* Treatment with oral or parenteral corticosteroids dosed greater than 40 mg hydrocortisone daily or its equivalent (e.g., prednisone 10 mg, prednisolone 8 mg, or decadron 3 mg) =\< 2 weeks of treatment initiation; or a clinical requirement for ongoing systemic immunosuppressive therapy
* History of central nervous system (CNS) metastases unless previously treated and stable for \> 8 weeks prior to study initiation
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
* Hypersensitivity to pegfilgrastim or Escherichia (E.) coli derived proteins