Title
A Phase 1, First-in-Human Study of MEN2312, a KAT6 Inhibitor, as Monotherapy and in Combination in Participants With Advanced Breast Cancer

Description
A Phase 1, First-in-Human Study of MEN2312, a KAT6 Inhibitor, as Monotherapy and in Combination in Participants With Advanced Breast Cancer

Objective
Primary Objectives:
-Parts A, C, E and G: To identify the MTD/MAD in Part A and recommended expansion doses (RDE) in Parts C, E and G for MEN2312 in advanced breast cancer.
-Parts D, F, and H: Establish the recommended phase 2 dose (RP2D) of MEN2312 when administered in combination.

Secondary Objectives in Monotherapy and Combination:
-Parts A, C, D, E, F, G and H: Evaluate the safety and tolerability of MEN2312 as monotherapy and in combination.
-Parts A, C, D, E, F, G and H: To evaluate preliminary antitumor activity of MEN2312.
-Part A: Characterize the PK profile of MEN2312 in plasma and urine and evaluate the effect of food on the PK when administered as monotherapy.
-Parts C, D, E, F G and H: Describe the PK profile of MEN2312 and other drugs when administered in combination.
-Parts C, D, E, F G and H: Evaluate PK DDI between MEN2312 and other drugs in combination.

Treatment This is a first-in-human study of MEN2312, a lysine acetyltransferase 6 (KAT6) inhibitor, in adult participants with advanced breast cancer.

Key Eligibility Key Inclusion Criteria:

Participant has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.

Participant must have received at least one prior line of endocrine therapy for advanced/metastatic disease or participant who has radiological evidence of breast cancer recurrence or progression during or within 12 months from the end of or during adjuvant treatment with endocrine therapy, as these participants are considered as first-line relapsed participants. Progression on previous cyclin-dependent kinase 4/6 inhibitor treatment in combination with fulvestrant or aromatase inhibitor is required. No other therapeutic options are considered appropriate by the investigator.

Up to 6 prior lines of systemic therapy (including up to 2 prior lines consisting of chemotherapy, cytotoxic antibody drug conjugate, or a combination of both regimens) are allowed in the advanced/metastatic setting.

Presence of genetic alterations in PIK3CA/AKT1/PTEN in participants' tumor tissue.

Active or newly diagnosed central nervous system metastases.

Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement >50%.

Applicable Disease Sites
Breast

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital