Clinical trial NCT06784193: Study of OP-3136 in Advanced or Metastatic Solid Tumors
Official title: A Phase 1 First-in-Human, Open-Label, Multicenter Study of OP-3136 in Adult Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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)
Keywords: KAT6 Inhibitor
Histone Acetyltransferase (HAT) Inhibitor
Epigenetic
Lead sponsor: Olema Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-20
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Primary outcomes:
measure: Number of participants with dose-limiting toxicities in the Dose Escalation Arms
timeFrame: Up to 28 days
measure: Incidence of adverse events and laboratory abnormalities
timeFrame: Up to 26 months
Secondary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Up to 26 months
measure: Time to maximum concentration (Tmax)
timeFrame: Up to 26 months
measure: Area under the curve from time zero to 24 hours (AUC0-24)
timeFrame: Up to 26 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 26 months
measure: Duration of Response (DOR)
timeFrame: Up to 26 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 26 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: New Orleans
country: United States
facility: University Medical Center - New Orleans
state: Louisiana
city: Grand Rapids
country: United States
facility: START - Midwest
state: Michigan
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: START - San Antonio
state: Texas
city: West Valley City
country: United States
facility: START - Mountain Region
state: Utah
city: Adelaide
country: Australia
facility: Cancer Research South Australia
state: South Australia
Study officials:
References: