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

NCT06239467 | Recruiting Phase 1 FDA Drug

• 1 other identifier: OKI-219-101
• Study Type: interventional
• Target: 200
• Locations: 6 countries
• Sites: 34

Brief Summary

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.

Conditions

Advanced Cancer; Breast Cancer; Advanced Solid Tumors; PI3K Gene Mutation

Keywords

PI3K; Solid Tumor; Breast Cancer; OKI-219; trastuzumab; fulvestrant; H1047r; ribociclib; atirmociclib; tucatinib

Outcome Measures

Primary Outcomes (4)

• Identify maximum tolerated dose (MTD) of OKI-219 in monotherapy

  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

  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

  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

  rate of dose modifications

  Through last study dose, an average of 1 year

Secondary Outcomes (10)

• 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)

  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)

  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)

  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)

  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)

  Up to approximately 36 months

Study Arms (9)

Phase 1a: Part A Dose Escalation

EXPERIMENTAL

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

Drug: OKI-219

Phase 1b: Part B Dose Escalation

EXPERIMENTAL

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

Phase 1b: Part B Dose Optimization

EXPERIMENTAL

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

Phase 1b: Part C Dose Escalation

EXPERIMENTAL

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

Phase 1b: Part C Dose Expansion

EXPERIMENTAL

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

Phase 1b: Part D Dose Escalation

EXPERIMENTAL

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

Phase 1b: Part D Dose Expansion

EXPERIMENTAL

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

Phase 1b: Part E Dose Escalation

EXPERIMENTAL

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

Phase 1b: Part E Dose Expansion

EXPERIMENTAL

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

Interventions

OKI-219 DRUG

Oral twice daily

Phase 1a: Part A Dose Escalation; Phase 1b: Part B Dose Escalation; Phase 1b: Part B Dose Optimization; Phase 1b: Part C Dose Escalation; Phase 1b: Part C Dose Expansion; Phase 1b: Part D Dose Escalation; Phase 1b: Part D Dose Expansion; Phase 1b: Part E Dose Escalation; Phase 1b: Part E Dose Expansion

Fulvestrant DRUG

Intramuscular injection

Phase 1b: Part B Dose Escalation; Phase 1b: Part B Dose Optimization; Phase 1b: Part D Dose Escalation; Phase 1b: Part D Dose Expansion; Phase 1b: Part E Dose Escalation; Phase 1b: Part E Dose Expansion

Trastuzumab DRUG

Intravenous (IV)

Phase 1b: Part C Dose Escalation; Phase 1b: Part C Dose Expansion

Tucatinib DRUG

Oral twice daily

Phase 1b: Part C Dose Escalation; Phase 1b: Part C Dose Expansion

Atirmociclib DRUG

Oral twice daily

Phase 1b: Part D Dose Escalation; Phase 1b: Part D Dose Expansion

Ribociclib DRUG

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

Phase 1b: Part E Dose Escalation; Phase 1b: Part E Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OnKure, Inc.: lead

Study Sites (34)

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

RECRUITING

University of California San Diego UCSD

La Jolla, California, 92093, United States

RECRUITING

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90024, United States

RECRUITING

Hoag - Huntington Beach

Newport Beach, California, 92663, United States

RECRUITING

Regents of the University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Karmanos Cancer Insitute

Detroit, Michigan, 48201, United States

WITHDRAWN

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

RECRUITING

Stony Brook University

Stony Brook, New York, 11794, United States

RECRUITING

SCRI Oncology Partners - Nashville

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

UZ Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

GZA Hopsitals Campus Sint-Augustinus

Wilrijk, 2610, Belgium

RECRUITING

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

Dijon, 21079, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Hopital Lyon Sud

Pierre-Bénite, 69310, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Ospedale San Gerardo-ASST Monza

Monza, 20900, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, 20089, Italy

RECRUITING

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

NEXT Oncology Phase I Unit / IOB- Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

RECRUITING

Hospital Beata Maria Ana

Madrid, 28007, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

START - Madrid

Madrid, 28050, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; Trastuzumab; tucatinib; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

OnKure, Inc.

CONTACT

720-307-2892; info@onkure.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: February 2, 2024
• Study Start: February 26, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6); US (13); BE (3); ES (4); IT (3); KR (5)