Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial

Inclusion Criteria: * Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents * Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \[CPS\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations/rearrangements, including EGFR, ALK and ROS-1, will be excluded.) * Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1) * Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor) * Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \[CSCC\], basal cell carcinoma \[BCC\] and Merkel cell carcinoma \[MCC\]) * Hodgkin's lymphoma * Urothelial carcinoma * Cervical cancer with documented PD-L1 expression (CPS ≥ 1) * Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency * Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD) * Any cancer type with historical data suggesting an ORR \> 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.) * Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options * Presence of at least one measurable tumor, per RECIST v1.1 * Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.) * Eastern Cooperative Oncology Group (ECOG) performance score of 0-2 * Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L * Platelet count ≥ 75 × 10\^9/L * Hemoglobin ≥ 9 g/dL (NOTE: Participants may have been transfused) * Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \[ULN\] in participants with Gilbert's syndrome) * Estimated creatinine clearance ≥ 30mL/min according to the Cockcroft-Gault formula or according to local institutional standard * Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator * Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s) * Women of childbearing potential must have a negative serum or urine pregnancy test at screening * Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists Exclusion Criteria: * Prior exposure to any immune-checkpoint inhibitor for any reason * Residual adverse event(s) from prior therapy grade \> 1 (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator * Known active central nervous system (CNS) metastases and/or prior history of leptomeningeal cancer involvement * Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \[skin, bladder, cervical, colorectal, breast\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.) * Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows: * Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \[DNA\] is negative, this participant could be enrolled with close monitoring of HBV activities.) * Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.) * Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100/μL, viral load less than 200 copies/mL, and clinically stable on antiretroviral therapy \[ART\] for at least 3 months.) * These participants will be enrolled only after approval from the medical monitor * Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (\> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses \< 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \[e.g., contrast dye allergy\], nivolumab-related standard premedication, and/or treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk/benefit assessment.) * Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities * Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk/benefit assessment.) * Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis * Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study * Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \[chickenpox\], yellow fever, rabies, bacillus Calmette Guerin \[BCG\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.) * Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study * Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.) * Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk * Pregnant or breast-feeding woman