A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors

Part 1 - Monotherapy Dose Escalation and Expansion:

Part 1A - Monotherapy Dose Escalation Part 1A will evaluate increasing doses of IDE574 to assess safety, tolerability and to determine dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) or the recommended dose for expansion (RDE) in subjects with advanced or metastatic ER+, HER2- breast cancer, non-small cell lung cancer, castration-resistant prostate cancer and microsatellite-stable colorectal cancer.

Part 1B - Monotherapy Dose Expansion Part 1B will evaluate in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during monotherapy dose escalation Part 1A. In parallel, a basket cohort may be enrolled at or below the highest safe dose level(s) determined to be safe and tolerable in Part 1A.

Part 2 - Combination Dose Escalation and Expansion

Part 2A - IDE574 Combination Therapy with Fulvestrant Dose Escalation Part 2A will evaluate participants with ER+ HER2- advanced or metastatic breast cancer with escalating doses of IDE574 in combination with fulvestrant to assess safety, tolerability and to determine DLTs, MTD or RDE.

Part 2B - IDE574 Combination Therapy with Fulvestrant Dose Expansion Part 2B will be evaluated in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during combination dose escalation Part 2A.

Inclusion criteria

Archival Tissue sample for testing

• Part 1A - Participants with advanced or metastatic ER+, HER2- breast cancer, NSCLC, CRPC, and MSS colorectal adenocarcinoma who have progressed on/after at least one line of standard of care therapy or are intolerant to additional effective therapies.
• Parts 1B, 2A and 2B: Participants with ER+, HER2- breast cancer who have progressed after at least 1 prior line of treatment with an endocrine therapy and a CDK4/6 inhibitor
• Female participants with ER+, HER2- breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause (Parts 2A and B only)
• Female participants of nonchildbearing potential with ER+, HER2- breast cancer must meet at least 1 of the following criteria: Age ≥ 60 years or age <60 years with absence of menstruation for at least 12 months, or had prior removal of both ovaries
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1.
• Have adequate bone marrow, renal and liver function.
• Life expectancy of >3 months
• Able to safely administer and retain orally administered study treatment
• Able to comply with contraceptive/barrier requirements

Key Exclusion Criteria:

• Known symptomatic brain metastases or leptomeningeal metastasis
• Known primary CNS malignancy and any other malignancies within 2 years prior to the first dose with the exception of adequately treated localized tumor.
• Have impairment of GI function or GI disease that may significantly alter the absorption of IDE574.
• Have active liver or biliary disease.
• Have active, uncontrolled bacterial, fungal, or viral infection
• Have clinically significant cardiac abnormalities and/or blood clotting events within 6 months before the first dose
• If participants had adverse reactions to previous experimental antitumor treatment that have not recovered to Grade ≤ 1
• Prior irradiation to >25% of the bone marrow.
• Known or suspected hypersensitivity to IDE574/excipients or components (Parts 1 & 2) or fulvestrant/excipients or components (Part 2 only)