Phase 1 Study of OP-3136 in Advanced or Metastatic Solid Tumors
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).
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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.
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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT06784193
Intervention or treatment
DRUG: OP-3136
DRUG: Fulvestrant
DRUG: Palazestrant
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)
- Metastatic Breast Cancer
- Fulvestrant
- Palazestrant
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Research sites nearby
Closest Location:
Cancer Research South Australia
Select from list below to view details:
Cancer Research South Australia
Adelaide, South Australia, Australia
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Who is running the clinical trial?
Olema Pharmaceuticals, Inc.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part 1A Dose Escalation monotherapy
| Drug: OP-3136 |
EXPERIMENTAL: Part 1B Dose Escalation in combination with fulvestrant
| Drug: OP-3136, Drug: Fulvestrant |
EXPERIMENTAL: Part 1C Dose Escalation in combination with palazestrant
| Drug: OP-3136, Drug: Palazestrant |
EXPERIMENTAL: Part 2A Dose Expansion monotherapy - mBC
| Drug: OP-3136 |
EXPERIMENTAL: Part 2A Dose Expansion monotherapy - mCRPC
| Drug: OP-3136 |
EXPERIMENTAL: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1
| Drug: OP-3136, Drug: Fulvestrant, Drug: Palazestrant |
EXPERIMENTAL: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2
| Drug: OP-3136, Drug: Fulvestrant, Drug: Palazestrant |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose-limiting toxicities in the Dose Escalation Arms | Not Specified | Up to 28 days |
| Incidence of adverse events and laboratory abnormalities | Not Specified | Up to 26 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed concentration (Cmax) | Not Specified | Up to 26 months |
| Time to maximum concentration (Tmax) | Not Specified | Up to 26 months |
| Area under the curve from time zero to 24 hours (AUC0-24) | Not Specified | Up to 26 months |
| Overall Response Rate (ORR) | Not Specified | Up to 26 months |
| Duration of Response (DOR) | Not Specified | Up to 26 months |
| Clinical Benefit Rate (CBR) | Not Specified | Up to 26 months |
References
Clinical Trials Gov: Phase 1 Study of OP-3136 in Advanced or Metastatic Solid TumorsOther trials to consider
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