Phase 1 Study of OP-3136 in Advanced or Metastatic Solid Tumors

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 tumorthat is unresectable or metastatic and for which life prolonging measures do notexist or available therapies are intolerable or no longer effective.

• Part 1B (Dose escalation for OP-3136 in combination with fulvestrant): Participantswith advanced or metastatic ER+ HER2- breast cancer that have progressed on or afterat least 1 prior line of treatment that included endocrine therapy and CDK 4/6inhibitor in advanced or metastatic setting and must have received no more than 2prior lines of endocrine therapy (one of which must be in combination with CDK4/6inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drugconjugate in the advanced or metastatic setting.

• Part 1C (Dose escalation for OP-3136 in combination with palazestrant): Participantswith advanced or metastatic ER+ HER2- breast cancer that have progressed on or afterat least 1 prior line of treatment that included endocrine therapy and CDK 4/6inhibitor in advanced or metastatic setting and must have received no more than 2prior lines of endocrine therapy (one of which must be in combination with CDK4/6inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drugconjugate in the advanced or metastatic setting.

• Part 2A (Dose Expansion in ER+ HER2- mBC for OP-3136 monotherapy): Participants musthave received up to 3 prior lines of endocrine therapy (one of which must be incombination with CDK4/6 inhibitor) and up to 1 prior line of chemotherapy or anantibody-drug conjugate.

• Part 2A (Dose Expansion in mCRPC for OP-3136 monotherapy): Participants must havereceived up to 4 lines of prior systemic therapy for prostate cancer. Prior therapymust include treatment with an androgen receptor pathway inhibitor(s).

• Part 2B (Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with fulvestrantOR 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 treatmentthat included endocrine therapy and CDK 4/6 inhibitor in advanced or metastaticsetting. Participants must have received no more than 2 prior lines of endocrinetherapy in the advanced or metastatic setting and no more than 1 prior line ofchemotherapy 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 atrisk of life-threatening complications in the short term.

• Known active or symptomatic central nervous system (CNS) metastases, carcinomatousmeningitis, leptomeningeal disease, or a spinal cord compression that requireCNS-specific treatment, or participants who did not demonstrate clinical andradiologic stability during the last 2 months prior to the first dose of studytreatment or require or are currently on steroid therapy for CNS metastases.

• History of cerebral vascular disease, including transient ischemic attack, within 6months prior to the first dose of study treatment.

• History of or ongoing impaired cardiac function or clinically significant cardiacdisease within 6 months prior to the first dose of study treatment.

Note: Additional inclusion/exclusion criteria may apply.