DFF332 as a Single Agent and in Combination With Everolimus & Immuno-Oncology Agents in Advanced/Relapsed Renal Cancer & Other Malignancies

Exclusion Criteria

• •1. History of seizure disorder \& extrapyramidal (EPS) symptoms
• •2. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• •* Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension
• •* Patients with corrected QT using the Fridericia's correction (QTcF) \> 470 msec for all patients on screening ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina \< 3 months prior to study entry
• •* History of stroke or transient ischemic event requiring medical therapy
• •* Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
• •3. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
• •1. ≤ 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.
• •2. ≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.
• •3. ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C.
• •4. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.
• •5. Patients who have undergone major surgery ≤ 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure.
• •4. Patient previously treated with a HIF2α inhibitor.
• •5. Uncontrolled concurrent illness including, but not limited to, ongoing active infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active bleeding diatheses, including any Patient known to have evidence of acute or chronic hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts.
• •6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• •7. Presence of Grade ≥ 2 toxicity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted), ototoxicity, and alopecia.
• •8. Pregnant or nursing (lactating) women