RTX-240 Monotherapy and in Combination With Pembrolizumab

Inclusion Criteria: * Signed written informed consent obtained prior to study procedures * Patients ≥18 years with an ECOG 0 or 1 (Parts 1, 2 and 4) or 0-2 (Part 3). * Relapsed/Refractory (R/R) or locally advanced, unresectable solid tumor for which no standard therapy exists (Parts 1, 2 and 4), or for which the patient is ineligible or has declined standard therapy or R/R, cytologically confirmed AML (Part 3). * Disease must be measurable per Response Evaluation Criteria * The shorter of 28 days or 5 half-lives must have elapsed since the completion of prior therapy, before initiation of study treatment. * Adequate Organ Function and Blood Cell Counts (Parts 1, 2, and 4) as defined by the protocol: * GFR ≥ 50 mL/min/1.73, * AST and ALT ≤ 3 × the ULN and total bilirubin ≤ 1.5 × ULN, in the absence of cancer within the liver * Or AST and ALT ≤ 5 × ULN and total bilirubin ≤ 3 × ULN, in the setting of primary or metastatic liver tumors. * ANC ≥ 1 × 10\^3/μL without myeloid growth factor support for at least one week prior to enrollment * Platelet count ≥ 75 × 10\^3/μL * Hemoglobin should be ≥ 9 g/dL without red blood cell transfusion for at least one week * Patients must have LVEF ≥ 45% * Patients enrolling into Part 2 of the study must be diagnosed with NSCLC, RCC, or anal cancers * Patients enrolling into Part 4 must be diagnosed with NSCLC or RCC * Patients enrolling into either Part 2 or 4 must have 2 or fewer prior treatment regimens. If patient received a prior PD-1/PD-L1-containing regimen, a prior response is required. Exclusion Criteria: * Primary central nervous system (CNS) malignancy or CNS involvement, unless asymptomatic, previously treated, and stable without steroids (Parts 1, 2 and 4) or known CNS leukemia (Part 3). * Known hypersensitivity to any component of study treatment or excipients. * Positive antibody screen using institution's standard type and screen test. * Clinically significant, active and uncontrolled infection, including human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV). * Clinically significant coagulopathy, uncontrolled hypertension or autoimmune hemolytic anemia * Class III or IV cardiomyopathy per the New York Heart Association criteria * Leukemic blast count ≥ 25 x 10\^3/µL (Part 3) * Concomitant conditions requiring active immunosuppression * History of clinically significant Grade 3 or higher immune related Adverse Event (irAE) * Prior malignancy within the past 3 years, with protocol specified exceptions * History of severe hypersensitivity to a PD-1/PD-L1 blocking Ab unless previously rechallenged successfully (Part 4) * Current noninfectious pneumonitis or a history of radiation pneumonitis or pneumonitis that required steroids, or Grade 2 or greater immune related pneumonitis, hepatitis, hypophysitis, or other endocrinopathy (Part 4)