Phase 1 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

Overview

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.

Interventions

• Drug OP-3136
  Selective inhibitor of HAT enzymes KAT6A and KAT6B
• Drug Fulvestrant
  Selective estrogen receptor degrader (SERD)
• Drug Palazestrant
  Complete estrogen receptor antagonist (CERAN)

Primary outcome measures

• 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 outcome measures (6)

• 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

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.

Note: Additional inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Florida Cancer Specialists — Sarasota
• University Medical Center - New Orleans — New Orleans
• Dana-Farber Cancer Institute — Boston
• START - Midwest — Grand Rapids
• SCRI Oncology Partners — Nashville
• START - San Antonio — San Antonio
• START - Mountain Region — West Valley City

Australia · 1 center

• Cancer Research South Australia — Adelaide

Identifiers

NCT: NCT06784193 · OP-3136-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗