First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer

Prior treatment

• Treatment with any investigational product or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, of the start of treatment
• Major surgery or wide-field radiation within 28 days or limited field palliative radiation within 7 days prior to the first dose of study drug.

Other illness

• Known active central nervous system metastasis, including leptomeningeal disease.
• Concomitant active malignancy or previous malignancy within 2 years of the time of enrollment.
• Impaired cardiovascular function or clinically significant cardiovascular disease,
• History of symptomatic drug-induced pneumonitis.
• Participants with active HIV, Hepatitis B, and Hepatitis C viral infections
  • Additional Cohort-specific key exclusion criteria:
  • Part C:
• History of chronic liver disease.
  • Part E:
  • ● History of interstitial lung disease.

Lab values

• Uncontrolled Type 1 or Type 2 diabetes as defined by HbA1C ≥ 8%.

Other

• Participants with a known KRAS mutation.
• Participants with a known deleterious mutation in phosphatase and tensin homolog (PTEN) or negative for PTEN protein expression by IHC.
• Grade 2 or higher diarrhea at study entry.

• Participants with advanced solid tumors with documented evidence of a PI3KαH1047R mutation in tumor tissue and/or blood (ie, ctDNA).
• Eastern Cooperative Oncology Group (ECOG) Performance status score of to 1.
• Life expectancy \> 12 weeks for Part A and \> 6 months for Parts B, C, D, and E in the opinion of the Investigator.
• Adequate organ and bone marrow function
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
• At least 1 measurable lesion based on RECIST version 1.1.
  • Additional Cohort-specific key inclusion criteria:
  • Part A
• Participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer, must have received at least 1 prior line of hormonal therapy and at least 1 prior line of CDK4/6-inhibitor in the advanced or metastatic setting.
• Participants with HER2+ locally advanced, unresectable or metastatic breast cancer, must have received prior taxane, trastuzumab, pertuzumab, and tucatinib. Prior trastuzumab deruxtecan is allowed but not required.
• Participants with HER2-low breast cancer must have received prior trastuzumab deruxtecan.
• Participants with colorectal cancer must have KRAS wild-type disease.
  • Part B
• Participants with locally advanced, unresectable or metastatic HR+/HER2- breast cancer must have received at least 1 prior line of hormonal therapy in the advanced or metastatic setting and at least 1 prior CDK4/6-inhibitor.
• Participants with HER2-low breast cancer should have received prior trastuzumab deruxtecan
  • Part C ● Participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer must have received prior taxane, trastuzumab, and pertuzumab unless unavailable in the region or contraindicated. Prior trastuzumab deruxtecan is allowed but not required.
  • Part D
  • ● Participants must have HR+/HER2- locally advanced, unresectable or metastatic breast cancer
  • Part E ● Participants must have HR+/HER2- locally advanced, unresectable or metastatic breast cancer.