IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of oral glutaminase inhibitor IPN60090 (IACS-6274) as monotherapy (Part A) and in combination therapy with bevacizumab and weekly paclitaxel (Part B) and in combination with capivasertib (Part C) II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IACS-6274 in combination with bevacizumab and weekly paclitaxel (Part B). and of the combination of IACS-6274 and capivasertib (Part C). (For Dose Escalation Only) SECONDARY OBJECTIVES: I. To assess the preliminary antitumor activity of IACS-6274 as monotherapy (Part A) in patients with or without biomarker selected tumor types. II. To assess the preliminary antitumor activity of IACS-6274 in the combination with bevacizumab and weekly paclitaxel (Part B) in patients with recurrent platinum-resistant ovarian cancer and in combination with capivasertib (Part C) for all solid tumors. III. To characterize the pharmacokinetics (PK) profile of IACS-6274 as a monotherapy (Part A) and in combination with bevacizumab and weekly paclitaxel (Part B) in the combination with capivasertib (Part C). To evaluate biomarkers of patient stratification and correlate them with clinical outcome. EXPLORATORY OBJECTIVE: I. To collect biobank samples for potential future analysis of biomarkers (optional, informed consent required). OUTLINE: This is a dose-escalation study of IACS-6274 followed by a dose-expansion study. Patients are assigned to 1 of 2 parts. PART A: Patients receive IACS-6274 orally (PO) throughout the study. PART B: Patients receive IACS-6274 PO, paclitaxel intravenously (IV), and bevacizumab IV throughout the study. PART C: Patients receive IACS-627 PO, with capivasertib PO throughout the study.