A Phase 1 interventional study of OKI-219 and Fulvestrant in Advanced Cancer, Breast Cancer and Advanced Solid Tumors, sponsored by OnKure, Inc.. Active, not recruiting at 33 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by OnKure, Inc. · Phase 1, Interventional, and Treatment
OKI-219-101 is a Phase 1a/1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of OKI-219 as monotherapy and in combination with other anti-cancer drugs. 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 fulvestrant (Part B), trastuzumab and tucatinib (Part C), atirmociclib (Part D), and ribociclib and fulvestrant (Part E). Participants will continue to receive study treatment until disease progression, intolerable toxicity, or other study treatment withdrawal criteria are met.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's planned enrollment of 200 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →OnKure, Inc. is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Additional Cohort-specific key inclusion criteria:
Part A
Part B
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:
Additional Cohort-specific key exclusion criteria:
Part C:
Part E:
● History of interstitial lung disease.
OKI-219 Monotherapy Dose Escalation in participants with advanced solid tumors with the PI3KαH1047R mutation
Drug: OKI-219
OKI-219 + Fulvestrant Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant
OKI-219 + Fulvestrant Dose Optimization in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant
OKI-219 + Tucatinib + Trastuzumab Dose Escalation in participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Trastuzumab · Drug: Tucatinib
OKI-219 + Tucatinib + Trastuzumab Dose Expansion in participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Trastuzumab · Drug: Tucatinib
OKI-219 + Fulvestrant + Atirmociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant · Drug: Atirmociclib
OKI-219 + Fulvestrant + Atirmociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant · Drug: Atirmociclib
OKI-219 + Fulvestrant + Ribociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant · Drug: Ribociclib
OKI-219 + Fulvestrant + Ribociclib Dose Expansion in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219 · Drug: Fulvestrant · Drug: Ribociclib
Oral twice daily
Intramuscular injection
Intravenous (IV)
Oral twice daily
Oral twice daily
Oral once daily continuous for 21-days followed by 7 days off
Identify maximum tolerated dose (MTD) of OKI-219 in monotherapy
Frequency of participants experiencing dose-limiting toxicities during the first 28-day cycle
Time frame: Cycle 1 (First 28 days on treatment)
Assess safety of OKI-219 as monotherapy or in combination with other anti-cancer therapies: incidence of SAEs
Number and type of SAEs experienced by participants during treatment and follow-up
Time frame: Through 30 days after last dose, an average of 1 year
Assess safety of OKI-219 as monotherapy or in combination with other anti-cancer therapies: incidence of Grade 2 or greater treatment emergent adverse events
Number of treatment-emergent adverse events (TEAEs) equal or greater than Grade 2 experienced during treatment and follow-up
Time frame: Through 30 days after last dose, an average of 1 year
Assess rate of dose modifications during treatment with OKI-219 as monotherapy or in combination with other anti-cancer therapies
rate of dose modifications
Time frame: Through last study dose, an average of 1 year
Assess the plasma PK of OKI-219 following single and multiple doses as monotherapy or in combination with other anti-cancer therapies: maximum plasma concentration (Cmax)
PK of OKI-219: Cmax
Time frame: Through cycle 6 of treatment (up to 28 weeks)
Assess the plasma PK of OKI-219 following single and multiple doses as monotherapy or in combination with other anti-cancer therapies: time of maximum plasma concentration (Tmax)
PK of OKI-219: Tmax
Time frame: Through cycle 6 of treatment (up to 28 weeks)
Assess the plasma PK of OKI-219 following single and multiple doses as monotherapy or in combination with other anti-cancer therapies: area under the plasma concentration-time curve (AUC)
PK of OKI-219: AUC
Time frame: Through cycle 6 of treatment (up to 28 weeks)
Assess the plasma PK of OKI-219 following single and multiple doses as monotherapy or in combination with other anti-cancer therapies: terminal elimination half-life time (t1/2)
PK of OKI-219: t1/2
Time frame: Through cycle 6 of treatment (up to 28 weeks)
To estimate the preliminary antitumor activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies: objective response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time frame: Up to approximately 36 months
To estimate the preliminary antitumor activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies: clinical benefit rate (CBR)
CBR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time frame: Up to approximately 36 months
Dose optimization only: to estimate the preliminary antitumor activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies: progression free survival (PFS)
PFS per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Time frame: Up to approximately 36 months
To assess the dose-response impact of OKI-219 as monotherapy and in combination with other anti-cancer therapies on PI3KαH1047R ctDNA levels
Changes in PI3KαH1047R ctDNA on treatment and end of treatment (EOT) compared to baseline.
Time frame: Through last study dose, an average of 1 year
To determine the impact of OKI-219 dosing as monotherapy and in combination with other anti-cancer therapies on blood glucose and insulin
Changes in plasma glucose, serum insulin, serum c-peptide levels, and hemoglobin A1c (HbA1c) will be evaluated on treatment compared to baseline.
Time frame: Through last study dose, an average of 1 year
To assess the PDx activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies
PDx activity will be evaluated with serial tumor biopsy samples assessed for PI3K/AKT/mTOR downstream pathway changes.
Time frame: Through last study dose, an average of 1 year
Plan to share: No
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This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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