Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program

Inclusion Criteria:

• Age ≥ 18 years

• Histologically confirmed malignancies for which treatment with intravenous nivolumabis currently Food and Drug Administration (FDA) approved and who are recommended toinitiate a new treatment regimen with single agent intravenous (IV) nivolumab bytheir treating oncologist for any of the indications outlined below and who arewilling to switch to subcutaneous nivolumab:

• Single agent nivolumab administered in the adjuvant setting for one of thefollowing indications:

• Completely resected stage IIB/C, III or IV melanoma

• Urothelial carcinoma status post radical resection and have a high risk ofrecurrence

• Completely resected esophageal or gastroesophageal junction carcinoma withresidual pathologic disease in adult patients who have receivedneoadjuvant chemoradiotherapy (CRT)

• Single agent nivolumab for advanced/metastatic cancer for one or more of thefollowing indications:

• Renal cell carcinoma (RCC) patients who have received prioranti-angiogenic therapy

• Non-small cell lung cancer (NSCLC) with progression on or afterplatinum-based chemotherapy (Note: patients with EGFR or ALK genomic tumoraberrations should have disease progression on FDA-approved therapy forthese aberrations prior to receiving nivolumab)

• Unresectable advanced, recurrent or metastatic esophageal squamous cellcarcinoma (ESCC) after prior fluoropyrimidine- and platinum-basedchemotherapy

• Unresectable or metastatic cutaneous melanoma

• Locally advanced or metastatic urothelial carcinoma who have diseaseprogression during or following platinum-containing chemotherapy or havedisease progression within 12 months of neoadjuvant or adjuvant treatmentwith platinum-containing chemotherapy

• Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy

• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed followingtreatment with a fluoropyrimidine, oxaliplatin, and irinotecan

• Patients transitioning to maintenance nivolumab and who are willing to switchto subcutaneous nivolumab after completion of Ipilimumab and nivolumabcombination therapy for one or more of the indications listed below (Note:patients who discontinue ipilimumab for immune-related toxicities, but aredeemed to be eligible to continue on single agent nivolumab maintenance bytheir treating oncologist are eligible):

• First-line treatment of adult patients with intermediate or poor riskadvanced renal cell carcinoma (RCC)

• Unresectable or metastatic cutaneous melanoma

• Hepatocellular carcinoma (HCC) previously treated with sorafenib

• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed followingtreatment with a fluoropyrimidine, oxaliplatin, and irinotecan

• Patients have recovered from the effects of any previous chemotherapy,immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (i.e., residual toxicity no worse than grade 1 [grade 2 treatment-associatedperipheral neuropathy, grade 2 fatigue and/or any grade of alopecia are acceptableassuming all other inclusion criteria are met]) before registration

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

• Aspartate transaminase (AST) values ≤ 3 × the upper limit of normal (ULN). Forpatients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase

• Alanine transaminase (ALT) values ≤ 3 x the upper limit of normal (ULN). Forpatients with documented baseline liver metastasis, the following limits will apply: 5 x ULN for transaminase

• Serum total bilirubin values of ≤ 1.5 x ULN ( ≤ 2 x ULN for patients with knownGilbert's syndrome). For patients with documented baseline liver metastasis, thefollowing limits will apply: 2 x ULN for bilirubin

• Absolute neutrophil count (ANC) of ≥ 1500/μL

• Platelet count of ≥ 100,000/μL

• Hemoglobin of ≥ 9 g/dL (patients may be transfused to this level, if necessary, buttransfusion must occur > 1 week prior to registration)

• Serum creatinine ≤ 2.0 x the ULN for the reference laboratory or a calculatedcreatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault Equation measured ≤ 7days prior to registration

• Patients are residing ≤ 35 miles of clinic (hub) or within the area serviced bysupplier and paramedic network

• Residence has Wi-Fi to enable a reliable connection with the remote command center

• Patients have signed Informed Consent Form (ICF)

• Patients are willing and able to comply with the study protocol in theinvestigator's judgment

• Patients are able and willing to complete study questionnaire(s) by themselves orwith assistance

• Women of childbearing potential (WOCBP) must:

• Have a negative pregnancy test (serum or urine) ≤ 3 days before the first doseof study drug

• Be agreeable to use a contraceptive method that is highly effective during theintervention period and for at least 5 months after the last dose and agreesnot to donate eggs (ova, oocytes) for the purpose of reproduction for the sametime period

Exclusion Criteria:

• Patients receiving any other investigational or standard of care agent which wouldbe considered as a treatment for the primary neoplasm and is not part of theeligible treatment regimen

• Patients requiring 24/7 assistance with activities of daily living (ADLs)

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens

• Uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Myocardial infarction ≤ 6 months

• Wound healing disorder

• Psychiatric illness/social situations that would limit compliance with studyrequirements

• Patients with any severe infection ≤ 4 weeks prior to registration including, butnot limited to, hospitalization for complications of infections

• Patients with an active, known or suspected autoimmune disease. Patients with type Idiabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, orconditions not expected to recur in the absence of an external trigger are permittedto enroll. Replacement therapy (e.g., thyroxine, insulin, or physiologiccorticosteroid replacement therapy for adrenal or pituitary insufficiency) is notconsidered a form of systemic treatment. Patients with vitiligo, Graves' disease, orpsoriasis not requiring systemic treatment within the past 30 days are not excluded.Patients with celiac disease controlled with diet modification are not excluded

• Patients with a condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalent) ≤ 14 days or other immunosuppressivemedications ≤ 30 days prior to registration. Inhaled or topical steroids, andadrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permittedin the absence of active autoimmune disease

• Concurrent malignancy (present during screening) requiring treatment or history ofprior malignancy active ≤ 2 years prior to registration (i.e., participants with ahistory of prior malignancy are eligible if treatment was completed at least 2 yearsbefore randomization/treatment assignment and the patient has no evidence ofdisease). Participants with history of prior early stage basal/squamous cell skincancer or non-invasive or in situ cancers that have undergone definitive treatmentat any time are also eligible

• Patients have undergone prior solid organ and/or non-autologous hematopoietic stemcell or bone marrow transplant

• Patients with active brain metastases or leptomeningeal metastases, aside from theexceptions below. Participants with brain metastases are eligible if they are:

• Asymptomatic

• Have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the central nervous system [CNS] treatment), and

• There is no MRI evidence of progression for at least 4 weeks after CNS directedtherapy is complete and ≤ 28 days prior to registration

• In addition, participants must have been either off corticosteroids, or on astable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for atleast 2 weeks prior to registration

• Participants with brain disease treated with whole brain radiation

• Anticipation of the need for major surgery during the course of study treatment

• Participants who are pregnant or breastfeeding

• Treatment with any live attenuated vaccines ≤ 30 days of registration (vaccines thatare not live attenuated are allowed, including COVID-19 vaccine)

• Known human deficiency virus (HIV) positive with an AIDS defining opportunisticinfection within the last year, or a current CD4 count < 350 cells/uL, aside fromthe exceptions below. Participants with HIV are eligible if:

• They have received antiviral therapy (ART) for at least 4 weeks prior totreatment assignment as clinically indicated while enrolled in the study

• They continue on ART as clinically indicated while enrolled on study

• CD4 counts and viral load are monitored per standard of care by a localhealthcare provider

• History of allergy or hypersensitivity to study drug components

• Any positive test result for hepatitis B virus (HBV) indicating presence of virus (e.g., hepatitis B surface antigen [HBsAg, Australia antigen]) positive

• Any positive test result for hepatitis C virus (HCV) indicating presence of activeviral replication (detectable HCV-ribonucleic acid [RNA]). Note: Participants withpositive HCV antibody and an undetectable HCV RNA are eligible to enroll