Study to Assess the Effect of OCT-598 in Patients With Advanced Solid Tumors

A Phase 1 Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OCT-598 as a Single Agent and in Combination With Standard-of-Care Treatment in Patients With Advanced Solid Tumors

This is a Phase 1 study intended to determine the MTD of OCT-598 following multiple-dose therapy and to establish the RP2D for OCT-598 as a single agent, by assessing its safety and tolerability as monotherapy and in combination with standard-of-care treatments in patients with advanced solid tumors.

Inclusion Criteria:

• Female or male, ≥18 years of age (or ≥19 years according to according to the local regulatory guidance), at the time of screening

• Signed informed consent prior to any study-related procedures that are not considered standard of care

• Life expectancy >12 weeks in the opinion of the investigator

• Adequate organ and marrow function, defined as follows:

  • Absolute neutrophil count ≥1.5 × 109/L
  • Platelets ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • Total bilirubin <1.5 × ULN
  • ALT or AST ≤2.5 × ULN
  • Creatinine clearance calculated using the Cockcroft-Gault formula ≥60 mL/min (In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately)

• LVEF >50% or within institutional values

• At least 1 measurable lesion based on RECIST version 1.1

• Cohort-specific disease requirements:

  1. Part A: patients with advanced solid tumors and no effective standard therapy option or for whom standard-of-care treatment is not available or not appropriate as per the investigator's discretion
  2. Part B: patients with advanced solid tumors who are candidates for receiving docetaxel as a single agent for their cancer treatment, including but not limited to: advanced human epidermal growth factor receptor 2-negative breast cancer, recurrent/metastatic head and neck cancer, non-small cell lung cancer, prostate cancer, or gastric/gastroesophageal cancer

• Docetaxel-appropriate (Part B): patients who have not received prior docetaxel in the advanced setting are eligible

Exclusion Criteria:

• Treatment with any IP or other anticancer therapy (including chemotherapy, antibody-drug conjugates, targeted agents, and immunotherapy) within 28 days or 5 half-lives, whichever is longer, of the first dose of study drug.
• Prior clinically significant treatment-related toxicities not resolved to Grade ≤1 or baseline (per CTCAE version 5.0) except for alopecia. Participants with stable Grade 2 peripheral neuropathy or endocrinopathies with stable endocrine replacement therapy are eligible. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment (eg, vitiligo or hearing loss) may be eligible after discussion with the Sponsor.
• Prior treatment with an EP2 and/or EP4 antagonist.
• Major surgery or wide-field radiation within 28 days or limited field palliative radiation within 7 days prior to the first dose of the study drug.
• Known active central nervous system metastasis. Patients with asymptomatic previously treated brain metastasis are eligible if they are clinically stable for at least 4 weeks prior to enrollment and do not require treatment with corticosteroids.
• Treatment with systemic corticosteroids at a dose of >10 mg of prednisone or equivalent at the time of enrollment, or any other immunosuppressive medication 7 days before the first dose of the study drug. Premedication with corticosteroids prior to chemotherapy administration in the combination phase is allowed, as per the site standard of care. Systemic treatment with NSAIDs, COX2 inhibitors, or synthetic prostaglandins within 5 half-lives prior to the first dose of study drug (acetylsalicylic acid ≤160 mg/day, or 325 mg ≤3 times/week is permitted).
• Patients who are pregnant, breastfeeding, or planning to become pregnant during the study .
• Concomitant active malignancy or previous malignancy within 2 years of the time of enrollment. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ or the cervix or breast, stage 1 prostate cancer, or other malignancy deemed to be cured by prior therapy in the judgment of the investigator may enroll regardless of the time of diagnosis.
• History of bleeding disorders, including gastrointestinal bleeding. Subjects with prior gastrointestinal bleeding due to the primary tumor, that is currently controlled, are allowed to participate.
• Mean resting corrected QT (QTc) interval using Fridericia's formula (QTcF) >470 ms, regardless of gender, or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome). Patients with left bundle block or atrial fibrillation are eligible if QTc cannot be accurately calculated provided that there is no prior history of prolonged QTc.
• For patients in Part B only: AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN.