NCT06239467
First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentOnKure, Inc.
~200 participants
Updated 2026-07-06 on ClinicalTrials.gov
What's tested:OKI-219FulvestrantTrastuzumabTucatinibAtirmociclibRibociclib
At a glance
Recruiting sites
0 of 33 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Identify maximum tolerated dose (MTD) of OKI-219 in monotherapy
Measured over Cycle 1 (First 28 days on treatment)
+3 more outcomes measured
Conditions
Where it's being run
33 sites across 13 statesFrance6
South Korea5
California4
Spain4
Belgium3
Italy3
Colorado2
Massachusetts1
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
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.
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
Exclusion
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
Grade 2 or higher diarrhea at study entry.
History of chronic liver disease.
What this trial measures
- Identify maximum tolerated dose (MTD) of OKI-219 in monotherapyCycle 1 (First 28 days on treatment)
Frequency of participants experiencing dose-limiting toxicities during the first 28-day cycle
- Assess safety of OKI-219 as monotherapy or in combination with other anti-cancer therapies: incidence of SAEsThrough 30 days after last dose, an average of 1 year
Number and type of SAEs experienced by participants during treatment and follow-up
- Assess safety of OKI-219 as monotherapy or in combination with other anti-cancer therapies: incidence of Grade 2 or greater treatment emergent adverse eventsThrough 30 days after last dose, an average of 1 year
Number of treatment-emergent adverse events (TEAEs) equal or greater than Grade 2 experienced during treatment and follow-up
- Assess rate of dose modifications during treatment with OKI-219 as monotherapy or in combination with other anti-cancer therapiesThrough last study dose, an average of 1 year
rate of dose modifications