First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer (PIKture-01)

July 1, 2026 updated by: OnKure, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Anderlecht, Belgium, 1070
        • Institut Jules Bordet
      • Leuven, Belgium, 3000
        • UZ Leuven - Campus Gasthuisberg
      • Wilrijk, Belgium, 2610
        • GZA Hopsitals Campus Sint-Augustinus
  • France
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer CLCC - Centre Georges Francois Leclerc (CGFL)
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69008
        • Centre Léon Bérard
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Pierre-Bénite, France, 69310
        • Hopital Lyon Sud
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Italy
      • Milan, Italy, 20132
        • Ospedale San Raffaele
      • Monza, Italy, 20900
        • Ospedale San Gerardo-ASST Monza
      • Rozzano, Italy, 20089
        • Istituto Clinico Humanitas
  • South Korea
      • Incheon, South Korea, 21565
        • Gachon University Gil Medical Center
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 05505
        • Asan Medical Center
      • Seoul, South Korea, 06351
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Severance Hospital
  • Spain
      • Barcelona, Spain, 08023
        • NEXT Oncology Phase I Unit / IOB- Hospital Quironsalud Barcelona
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital Beata Maria Ana
      • Madrid, Spain, 28050
        • START - Madrid
  • United States
    • California
      • Encinitas, California, United States, 92024
        • California Cancer Associates for Research and Excellence
      • La Jolla, California, United States, 92093
        • University of California San Diego UCSD
      • Los Angeles, California, United States, 90024
        • UCLA Jonsson Comprehensive Cancer Center
      • Newport Beach, California, United States, 92663
        • Hoag - Huntington Beach
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Regents of the University of Colorado
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institute at HealthONE
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Stony Brook, New York, United States, 11794
        • Stony Brook University
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI Oncology Partners - Nashville
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • NEXT Oncology Virginia
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1b: Part B Dose Escalation
OKI-219 + Fulvestrant Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Experimental: Phase 1b: Part B Dose Optimization
OKI-219 + Fulvestrant Dose Optimization in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation
Drug: OKI-219
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Experimental: Phase 1a: Part A Dose Escalation
OKI-219 Monotherapy Dose Escalation in participants with advanced solid tumors with the PI3KαH1047R mutation
Drug: OKI-219
Oral twice daily
Experimental: Phase 1b: Part C Dose Escalation
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
Oral twice daily
Drug: Trastuzumab
Intravenous (IV)
Drug: Tucatinib
Oral twice daily
Experimental: Phase 1b: Part C Dose Expansion
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
Oral twice daily
Drug: Trastuzumab
Intravenous (IV)
Drug: Tucatinib
Oral twice daily
Experimental: Phase 1b: Part D Dose Escalation
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
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Drug: Atirmociclib
Oral twice daily
Experimental: Phase 1b: Part D Dose Expansion
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
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Drug: Atirmociclib
Oral twice daily
Experimental: Phase 1b: Part E Dose Escalation
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
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Drug: Ribociclib
Oral once daily continuous for 21-days followed by 7 days off
Experimental: Phase 1b: Part E Dose Expansion
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
Oral twice daily
Drug: Fulvestrant
Intramuscular injection
Drug: Ribociclib
Oral once daily continuous for 21-days followed by 7 days off

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identify maximum tolerated dose (MTD) of OKI-219 in monotherapy
Time Frame: Cycle 1 (First 28 days on treatment)
Frequency of participants experiencing dose-limiting toxicities during the first 28-day cycle
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
Time Frame: Through 30 days after last dose, an average of 1 year
Number and type of SAEs experienced by participants during treatment and follow-up
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
Time Frame: Through 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
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
Time Frame: Through last study dose, an average of 1 year
rate of dose modifications
Through last study dose, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Through cycle 6 of treatment (up to 28 weeks)
PK of OKI-219: Cmax
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)
Time Frame: Through cycle 6 of treatment (up to 28 weeks)
PK of OKI-219: Tmax
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)
Time Frame: Through cycle 6 of treatment (up to 28 weeks)
PK of OKI-219: AUC
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)
Time Frame: Through cycle 6 of treatment (up to 28 weeks)
PK of OKI-219: t1/2
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)
Time Frame: Up to approximately 36 months
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
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)
Time Frame: Up to approximately 36 months
CBR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
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)
Time Frame: Up to approximately 36 months
PFS per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
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
Time Frame: Through last study dose, an average of 1 year
Changes in PI3KαH1047R ctDNA on treatment and end of treatment (EOT) compared to baseline.
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
Time Frame: Through last study dose, an average of 1 year
Changes in plasma glucose, serum insulin, serum c-peptide levels, and hemoglobin A1c (HbA1c) will be evaluated on treatment compared to baseline.
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
Time Frame: Through last study dose, an average of 1 year
PDx activity will be evaluated with serial tumor biopsy samples assessed for PI3K/AKT/mTOR downstream pathway changes.
Through last study dose, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OnKure, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

January 12, 2024

First Submitted That Met QC Criteria

January 25, 2024

First Posted (Actual)

February 2, 2024

Study Record Updates

Last Update Posted (Actual)

July 6, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OKI-219-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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