RTX-240 Monotherapy and in Combination With Pembrolizumab

Open to people ages 18 years and up

• 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 × 10³/μL without myeloid growth factor support for at least one week prior to enrollment

• Platelet count ≥ 75 × 10³/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.

• 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 10³/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)