Recruiting
Phase 1
Phase 1 Study of OP-3136 in Advanced or Metastatic Solid Tumors
Condition(s) studied
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)Metastatic Breast CancerFulvestrantPalazestrant
Investigational drug(s) / intervention(s)
OP-3136: Selective inhibitor of HAT enzymes KAT6A and KAT6B
Fulvestrant: Selective estrogen receptor degrader (SERD)
Palazestrant: Complete estrogen receptor antagonist (CERAN)
Study 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).
Eligibility
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 1A (Dose escalation for OP-3136 monotherapy): 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 1B (Dose escalation for OP-3136 in combination with fulvestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
* Part 1C (Dose escalation for OP-3136 in combination with palazestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
* Part 2A (Dose Expansion in ER+ HER2- mBC for OP-3136 monotherapy): 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 2A (Dose Expansion in mCRPC for OP-3136 monotherapy): 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).
* Part 2B (Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with fulvestrant OR Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with palazestrant): Participants must have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting. Participants must have received no more than 2 prior lines of endocrine therapy in the advanced or metastatic setting and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
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 outcome measure(s)
- Number of participants with dose-limiting toxicities in the Dose Escalation Arms — Up to 28 days
- Incidence of adverse events and laboratory abnormalities — Up to 26 months
Trial sites (25)
| Facility | City | Region | Status |
| Banner MD Anderson Cancer Center |
Gilbert |
Arizona |
Recruiting |
| University of Colorado |
Aurora |
Colorado |
Recruiting |
| Florida Cancer Specialists |
Sarasota |
Florida |
Recruiting |
| University Medical Center - New Orleans |
New Orleans |
Louisiana |
Terminated |
| Massachusetts General Hospital |
Boston |
Massachusetts |
Recruiting |
| Dana-Farber Cancer Institute |
Boston |
Massachusetts |
Recruiting |
| START - Midwest |
Grand Rapids |
Michigan |
Recruiting |
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
Recruiting |
| The Ohio State University |
Columbus |
Ohio |
Recruiting |
| SCRI Oncology Partners |
Nashville |
Tennessee |
Recruiting |
| Tennessee Oncology |
Nashville |
Tennessee |
Recruiting |
| START - San Antonio |
San Antonio |
Texas |
Recruiting |
| START - Mountain Region |
West Valley City |
Utah |
Recruiting |
| The Kinghorn Cancer Centre |
Darlinghurst |
New South Wales |
Recruiting |
| Liverpool Hospital |
Liverpool |
New South Wales |
Recruiting |
| Macquarie University Clinical Trials Unit |
Macquarie |
New South Wales |
Recruiting |
| Cancer Research South Australia |
Adelaide |
South Australia |
Recruiting |
| Institut De Cancerologie De L'ouest |
Saint-Herblain |
Loire-Atlantique |
Recruiting |
| Hôpital Paris Saint-Joseph |
Paris |
Paris |
Recruiting |
| Institut Gustave Roussy |
Villejuif |
Val-de-Marne |
Recruiting |
| Queen Mary Hospital |
Hong Kong |
Hong Kong |
Recruiting |
| START Dublin |
Dublin |
Dublin |
Recruiting |
| START - Barcelona |
Barcelona |
Barcelona |
Recruiting |
| Start - Fjd |
Madrid |
Madrid |
Recruiting |
| START Madrid - CIOCC |
Madrid |
Madrid |
Recruiting |
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