First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer

NCT ID: NCT06239467

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-26

Study Completion Date

2027-08-01

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Cancer Breast Cancer Advanced Solid Tumors PI3K Gene Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1a: Part A Dose Escalation

OKI-219 Monotherapy Dose Escalation in participants with advanced solid tumors with the PI3KαH1047R mutation

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Trastuzumab

Intervention Type DRUG

Intravenous (IV)

Tucatinib

Intervention Type DRUG

Oral twice daily

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Trastuzumab

Intervention Type DRUG

Intravenous (IV)

Tucatinib

Intervention Type DRUG

Oral twice daily

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

Atirmociclib

Intervention Type DRUG

Oral twice daily

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

Atirmociclib

Intervention Type DRUG

Oral twice daily

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

Ribociclib

Intervention Type DRUG

Oral once daily continuous for 21-days followed by 7 days off

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

Group Type EXPERIMENTAL

OKI-219

Intervention Type DRUG

Oral twice daily

Fulvestrant

Intervention Type DRUG

Intramuscular injection

Ribociclib

Intervention Type DRUG

Oral once daily continuous for 21-days followed by 7 days off

Interventions

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OKI-219

Oral twice daily

Intervention Type DRUG

Fulvestrant

Intramuscular injection

Intervention Type DRUG

Trastuzumab

Intravenous (IV)

Intervention Type DRUG

Tucatinib

Oral twice daily

Intervention Type DRUG

Atirmociclib

Oral twice daily

Intervention Type DRUG

Ribociclib

Oral once daily continuous for 21-days followed by 7 days off

Intervention Type DRUG

Eligibility Criteria

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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.


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


Part C:

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

Part E:

● History of interstitial lung disease.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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OnKure, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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California Cancer Associates for Research and Excellence

Encinitas, California, United States

Site Status RECRUITING

University of California San Diego UCSD

La Jolla, California, United States

Site Status RECRUITING

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Hoag - Huntington Beach

Newport Beach, California, United States

Site Status RECRUITING

Regents of the University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Karmanos Cancer Insitute

Detroit, Michigan, United States

Site Status WITHDRAWN

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status RECRUITING

Stony Brook University

Stony Brook, New York, United States

Site Status RECRUITING

SCRI Oncology Partners - Nashville

Nashville, Tennessee, United States

Site Status RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Institut Jules Bordet

Anderlecht, , Belgium

Site Status RECRUITING

UZ Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status RECRUITING

GZA Hopsitals Campus Sint-Augustinus

Wilrijk, , Belgium

Site Status RECRUITING

Centre de Lutte Contre le Cancer CLCC - Centre Georges Francois Leclerc (CGFL)

Dijon, , France

Site Status RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status RECRUITING

Hopital Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Ospedale San Raffaele

Milan, , Italy

Site Status RECRUITING

Ospedale San Gerardo-ASST Monza

Monza, , Italy

Site Status RECRUITING

Istituto Clinico Humanitas

Rozzano, , Italy

Site Status RECRUITING

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

NEXT Oncology Phase I Unit / IOB- Hospital Quironsalud Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Beata Maria Ana

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

START - Madrid

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Belgium France Italy South Korea Spain

Central Contacts

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OnKure, Inc.

Role: CONTACT

720-307-2892

Facility Contacts

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Dante Pasiliao

Role: primary

Jasmine Fernandez

Role: primary

Doris Quintanilla

Role: primary

Abigail Lazo

Role: primary

Leah Adams

Role: primary

Jessica Ellis

Role: primary

Jennifer Petersen

Role: primary

Elizabeth Hutchings

Role: primary

Pushpa Talanki

Role: primary

Gretchen Johnston

Role: primary

Blake Patterson

Role: primary

Kaysey Hermens

Role: primary

Pierre-Andre Bouchonville

Role: primary

Inge Van Uffel

Role: primary

Caroline Merckx

Role: primary

Peggy Philippe

Role: primary

Amelie Decourcelle

Role: primary

Amelie Vey

Role: primary

Jennifer Oudard

Role: primary

Christine Gerentet

Role: primary

Djedjiga Oudni

Role: primary

Jessica Filoni

Role: primary

Edoardo Mauri

Role: primary

Andrea Camorani

Role: primary

Hyerim Choi

Role: primary

Yuri Ko

Role: primary

Jieun Kim

Role: primary

Mi Yeon Park

Role: primary

Inkyung Jung

Role: primary

Abigail Huerta

Role: primary

Pilar Chaparro

Role: primary

Raquel Rodriguez

Role: primary

Irene Valderrama

Role: primary

Other Identifiers

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OKI-219-101

Identifier Type: -

Identifier Source: org_study_id

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