This is a first-in-human, open-label, multicenter phase 1 study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, as monotherapy and in combination with other anticancer agents 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 1A (Dose Escalation for OP-3136 Monotherapy): 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 1B (Dose Escalation for OP-3136 in Combination with Fulvestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with fulvestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination. Part 1C (Dose Escalation for OP-3136 in Combination with Palazestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with palazestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination. Part 2A (Dose Expansion for OP-3136 Monotherapy): This part will evaluate two expansion cohorts at the monotherapy RDE from part 1 in participants with ER+ HER2- mBC and participants with mCRPC. Part 2B (Dose Expansion for OP-3136 in Combination with Fulvestrant OR Palazestrant): This part will evaluate the RDEs for OP-3136 in combination with fulvestrant from Part 1B OR the RDEs of OP-3136 in combination with palazestrant in an expansion cohort in participants with ER+ HER2- mBC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
Selective inhibitor of HAT enzymes KAT6A and KAT6B
Selective estrogen receptor degrader (SERD)
Complete estrogen receptor antagonist (CERAN)
Florida Cancer Specialists
Sarasota, Florida, United States
RECRUITINGUniversity Medical Center - New Orleans
New Orleans, Louisiana, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGSTART - Midwest
Grand Rapids, Michigan, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGSTART - San Antonio
San Antonio, Texas, United States
RECRUITINGSTART - Mountain Region
West Valley City, Utah, United States
RECRUITINGCancer Research South Australia
Adelaide, South Australia, Australia
RECRUITINGNumber of participants with dose-limiting toxicities in the Dose Escalation Arms
Time frame: Up to 28 days
Incidence of adverse events and laboratory abnormalities
Time frame: Up to 26 months
Maximum observed concentration (Cmax)
Time frame: Up to 26 months
Time to maximum concentration (Tmax)
Time frame: Up to 26 months
Area under the curve from time zero to 24 hours (AUC0-24)
Time frame: Up to 26 months
Overall Response Rate (ORR)
Time frame: Up to 26 months
Duration of Response (DOR)
Time frame: Up to 26 months
Clinical Benefit Rate (CBR)
Time frame: Up to 26 months
There may be multiple sites in this clinical trial Olema Clinical Trial Lead
CONTACT
Olema Medical Study Director
CONTACT
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