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Testing OKI-219 for advanced solid tumors and breast cancer

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

Phase 1 Interventional OnKure, Inc. · NCT06239467

This study is testing a new drug called OKI-219 to see if it can safely help people with advanced solid tumors and breast cancer, both on its own and with other treatments.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexAll
SponsorOnKure, Inc. Industry-sponsored
Drugs / interventionstrastuzumab, pertuzumab, tucatinib, radiation
Locations34 sites (Encinitas, California and 33 other locations)
Trial IDNCT06239467 on ClinicalTrials.gov

What this trial studies

This Phase 1 study evaluates the safety and effectiveness of OKI-219, both alone and in combination with fulvestrant or trastuzumab, in patients with advanced solid tumors and advanced breast cancer. The study consists of two parts: the first part focuses on escalating doses of OKI-219 as a monotherapy, while the second part examines its use alongside standard treatments. Participants will be monitored for safety, tolerability, and treatment response until disease progression or unacceptable side effects occur.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced solid tumors harboring a specific PI3KαH1047R mutation and those with advanced breast cancer who have exhausted standard treatment options.

Not a fit: Patients without the PI3KαH1047R mutation or those who have not previously received standard therapies for their cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors and breast cancer that have limited treatment alternatives.

How similar studies have performed: While this approach is novel in its specific targeting of the PI3KαH1047R mutation, similar studies targeting other mutations have shown promise in treating advanced cancers.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* 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.

Key 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 key exclusion criteria:

Part C:

* Grade 2 or higher diarrhea at study entry.
* History of chronic liver disease.

Part E:

● History of interstitial lung disease.

Where this trial is running

Encinitas, California and 33 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced CancerBreast CancerAdvanced Solid TumorsPI3K Gene MutationPI3KSolid TumorOKI-219trastuzumab
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.