study of op-3136 in advanced or metastatic solid tumors

Conditions: Advanced or Metastatic ER+ HER2- Breast Cancer (mBC); Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC); Advanced or Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Summary: this is a first-in-human, open-label, multicenter phase 1 study to evaluate the safety, tolerability, pharmacokinetics (pk), pharmacodynamics (pd), and preliminary efficacy of op-3136, a lysine acetyltransferases 6a and 6b (kat6a/b) inhibitor, in participants with advanced solid tumors. this study consists of 2 parts: a dose escalation part (part 1) and dose expansion part (part 2).

part 1 (dose escalation): this part of the study will evaluate the safety, tolerability, and pk in a range of doses of op-3136, a lysine acetyltransferases 6a and 6b (kat6a/b) inhibitor, administered orally once daily to participants with er+ her2- advanced or metastatic breast cancer (mbc), advanced or metastatic castration resistant prostate cancer (mcrpc), or advanced or metastatic non-small cell lung cancer (mnsclc), and determine the maximum tolerated dose (mtd) and the recommended dose/regimen for expansion (rde). part 2 (dose expansion): this part will evaluate the recommended dose and regimen from part 1 in the expansion cohorts of participants with er+ her2- mbc and participants with mcrpc.

Eligibility criteria:
key inclusion criteria: * participants with advanced or metastatic er+her2- breast cancer, mcrpc, or nsclc (part 1) or advanced or metastatic er+her2- bc or mcrpc (part 2). * part 1 (dose escalation): participants must have a tumor that is unresectable or metastatic and for which life prolonging measures do not exist or available therapies are intolerable or no longer effective. * part 2 (dose expansion in er+ her2- mbc): participants must have received up to 3 prior lines of endocrine therapy (one of which must be in combination with cdk4/6 inhibitor) and up to 1 prior line of chemotherapy or an antibody-drug conjugate. * part 2 (dose expansion in mcrpc): participants must have received up to 4 lines of prior systemic therapy for prostate cancer. prior therapy must include treatment with an androgen receptor pathway inhibitor(s). key exclusion criteria: * prior therapy with kat6a/b inhibitor in any treatment setting. * participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term. * known active or symptomatic central nervous system (cns) metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require cns-specific treatment, or participants who did not demonstrate clinical and radiologic stability during the last 2 months prior to the first dose of study treatment or require or are currently on steroid therapy for cns metastases. * history of cerebral vascular disease, including transient ischemic attack, within 6 months prior to the first dose of study treatment. * history of or ongoing impaired cardiac function or clinically significant cardiac disease within 6 months prior to the first dose of study treatment. note: additional inclusion/exclusion criteria may apply.

Keywords: kat6 inhibitor histone acetyltransferase (hat) inhibitor epigenetic