PIKture-01: First-in-Human Study of the PI3KαH1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and as Part of Combination Therapy in Participants With Advanced Breast Cancer
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Study Summary
To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of OKI-219 as monotherapy and in combination with fulvestrant or trastuzumab. Phase 1a (Part A) will investigate escalating doses of OKI-219 monotherapy, and Phase 1b will investigate OKI-219 (at a tolerated dose determined in Part A) in combination with standard dose fulvestrant (Part B) or standard dose trastuzumab (Part C). Participants will continue to receive study treatment until disease progression, intolerable toxicity, or other study treatment withdrawal criteria are met. To hypothesize OKI-219 may achieve greater mutant target coverage with a wider therapeutic window compared to other non-selective PI3Kα inhibitors. The study also includes a dose optimization phase to evaluate the optimal combination doses of OKI219 with fulvestrant or trastuzumab.
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of OKI-219 as monotherapy and in combination with other anti-cancer drugs for the treatment of HR+ and HER2+ advanced breast cancer.
- 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.
- Exclusion Criteria:
- Treatment with any investigational product or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, of the start of treatment
- 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.
- 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.
- Known active central nervous system metastasis, including leptomeningeal disease.
- Uncontrolled Type 1 or Type 2 diabetes as defined by HbA1C ≥ 8%.
- 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
- Part C:
- Grade 2 or higher diarrhea at study entry.
- History of chronic liver disease.
- Part E:
- History of interstitial lung disease.
Clinical Study Information for Healthcare Providers
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