A Phase 1 First-in-Human, Open-Label, Multicenter Study of OP-3136 in Adult Participants With Advanced or Metastatic Solid Tumors
Summary
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).
Detailed description
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.
Arms & interventions
- DrugOP-3136
Selective inhibitor of HAT enzymes KAT6A and KAT6B
- DrugFulvestrant
Selective estrogen receptor degrader (SERD)
- DrugPalazestrant
Complete estrogen receptor antagonist (CERAN)
Outcome measures
Primary
Number 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
Secondary
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
Eligibility criteria
Study locations (7)
Florida Cancer Specialists
Sarasota, Florida, 34232
University Medical Center - New Orleans
New Orleans, Louisiana, 70112
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
START - Midwest
Grand Rapids, Michigan, 49546
SCRI Oncology Partners
Nashville, Tennessee, 37203
START - San Antonio
San Antonio, Texas, 78229
START - Mountain Region
West Valley City, Utah, 84119