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NCT06239467 | RECRUITING | Advanced Cancer

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

OnKure, Inc.

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 fulvestrant or trastuzumab. 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 standard dose fulvestrant (Part B) or standard dose trastuzumab (Part C). Participants will continue to receive study treatment until disease progression, intolerable toxicity, or other study treatment withdrawal criteria are met.

Condition or disease

Advanced Cancer

Breast Cancer

Intervention/treatment

OKI-219

Fulvestrant

Trastuzumab

Phase

PHASE1

Study Type : INTERVENTIONAL
Estimated Enrollment : 150 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : PIKture-01: First-in-Human Study of the PI3KαH1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and in Combination With Endocrine Therapy or HER2-Targeted Therapy in Participants With Advanced Breast Cancer
Actual Study Start Date : 2024-02-26
Estimated Primary Completion Date : 2026-06-01
Estimated Study Completion Date : 2027-08-01

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • 1. Participants with advanced solid tumors with documented evidence of a PI3KαH1047R mutation in tumor tissue and/or blood (ie, ctDNA) obtained during the course of normal clinical care in a Clinical Laboratory Improvement Amendments (CLIA)- or similarly certified laboratory.
  • 2. Cohort-specific disease requirements
    • 1. Phase 1a Monotherapy Dose Escalation (Part A)
      • * Participants with advanced solid tumors and no effective standard therapy option or for whom standard-of-care therapy is not available or not appropriate.
      • * 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 cyclin-dependent kinase (CDK)4/6-inhibitor in the advanced or metastatic setting unless contraindicated.
      • * Participants with HER2+ locally advanced, unresectable or metastatic breast cancer must have received prior taxane, trastuzumab, pertuzumab, tucatinib, and trastuzumab deruxtecan unless unavailable in the region or contraindicated.
      • * Participants with HER2-low breast cancer must have received prior trastuzumab deruxtecan unless unavailable in the region or contraindicated.
      • * Participants with colorectal cancer must have Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type disease.
      • 2. Phase 1a Monotherapy Backfill Additional Criterion (Part A)
        • - Participants must have a tumor amenable to predose, post dose and end-of- treatment tumor biopsy
        • 3. Phase 1b Dose Escalation and Dose Optimization: OKI-219 + fulvestrant (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 unless contraindicated or unavailable in the region.
          • * Participants must be post-menopausal or agree to ovarian suppression with a gonadotropin-releasing hormone (GnRH) agonist started at least 4 weeks prior to the first dose of study drug.
          • * Participants with HER2-low breast cancer must have received prior trastuzumab deruxtecan unless unavailable in the region or contraindicated.
          • * Candidate for fulvestrant therapy.
          • 4. Phase 1b Dose Escalation and Dose Optimization: OKI-219 + trastuzumab (Part C)
            • * Participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer must have received prior taxane, trastuzumab, pertuzumab, tucatinib, and trastuzumab deruxtecan unless unavailable in the region or contraindicated.
            • * Candidate for trastuzumab therapy.
            • * Left ventricular ejection fraction (LVEF) \> 50%
            • 3. ECOG PS 0 to 1.
            • 4. Life expectancy \> 12 weeks.
            • 5. Have adequate archival tumor tissue (block or 10 slides) from a core or surgical biopsy, excluding bone biopsies. If no archival tissue is available, a fresh biopsy must be performed.
            • 6. Adequate organ and marrow function, defined as follows
              • 1. Absolute neutrophil count ≥ 1.5 × 10\^9/L;
              • 2. Platelets ≥ 100,000/μL;
              • 3. Hemoglobin ≥ 8.0 g/dL;
              • 4. Total bilirubin within the institutional upper limit of normal (ULN);
              • 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
              • 6. Creatinine clearance calculated using the Cockcroft-Gault formula ≥ 60 mL/min.
              • 7. All prior clinically significant treatment-related toxicities must have resolved to Grade ≤ 1 or baseline (per CTCAE version 5.0) except for alopecia. Participants with stable Grade 2 peripheral neuropathy or endocrinopathies with stable endocrine replacement therapy are eligible. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment (eg, vitiligo or hearing loss) may be eligible after discussion with the Sponsor.
              • 8. Able to swallow and tolerate oral medications.
              • 9. At least 1 measurable lesion based on RECIST version 1.1.
              Exclusion Criteria
              • 1. Treatment with any investigational product or other anticancer therapy (including chemotherapy, antibody-drug conjugates, targeted agents, and immunotherapy) within 14 days or 5 half-lives, whichever is shorter, of the first dose of study drug.
              • 2. Prior treatment with the PI3KαH1047R mutant-selective inhibitor LOXO-783.
              • 3. Participants with a known KRAS mutation.
              • 4. Participants with a known deleterious mutation in PTEN or negative for PTEN protein expression by IHC.
              • 5. 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.
              • 6. Known active central nervous system metastasis.
              • 7. Treatment with systemic corticosteroids at a dose of \> 10 mg of prednisone or equivalent at the time of enrollment.
              • 8. Uncontrolled Type 1 or Type 2 diabetes.
              • 9. Known history of Crigler-Najjar syndrome.
              • 10. Known Gilbert's syndrome.
              • 11. Participants who are pregnant or nursing.
              • 12. Concomitant active malignancy or previous malignancy within 2 years of the time of enrollment.
              • 13. Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following
                • 1. History of acute myocardial infarction or acute coronary syndromes in the 6 months prior to enrollment.
                • 2. Symptomatic congestive heart failure (Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality in the last 6 months except for medically managed atrial fibrillation or paroxysmal supraventricular tachycardia.
                • 3. Uncontrolled hypertension despite medical management
                • 14. Any medical condition that would impair the administration or absorption of oral agents.
                • 15. History of symptomatic drug-induced pneumonitis.
                • 16. Participants with HIV infection and any of the following
                  • 1. Cluster of differentiation 4 (CD4) count \< 350 cells/μL;
                  • 2. A history of AIDS with an opportunistic infection within 12 months prior to enrollment;
                  • 3. Not on established antiretroviral therapy for at least 4 weeks prior to enrollment and HIV viral load \> 400 copies/mL.
                  • 17. Positive hepatitis B virus (HBV) core antibody unless antigen negative and HBV DNA polymerase chain reaction (PCR) is negative. In the case of participants with positive HBV core antibody with antigen negative and negative HBV DNA PCR, the Investigator should consider the use of prophylaxis for reactivation.
                  • 18. Positive hepatitis C virus (HCV) antibody unless PCR negative for HCV RNA with completion of curative antiviral treatment.
                  • 19. History or current evidence of congenital long QT syndrome.
                  • 20. QTc interval corrected using Fridericia's formula (QTcF) \> 470 msec on screening ECG.
                  • 21. Use of any of the following within 1 week prior to the first dose of study drug or ongoing need for these medications throughout the treatment phase
                    • 1. Proton pump inhibitors (PPIs);
                    • 2. Medications that are moderate or strong inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)2B7;
                    • 3. Sensitive substrates of organic anion transporter (OAT)1, OAT3, breast cancer resistance protein (BCRP), or OATP1B1 with known risk for clinically relevant drug interactions related to transporter inhibition (note: the 1-week washout period prior to the first dose is not necessary for these substrates).
First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer

Location Details

NCT06239467

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, California

California Cancer Associates for Research and Excellence

Encinitis, California, United States, 92024

RECRUITING

United States, California

University of California San Diego UCSD

THE JOLLA, California, United States, 92093

RECRUITING

United States, California

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, United States, 90024

RECRUITING

United States, California

Hoag - Huntington Beach

Newport Beach, California, United States, 92663

RECRUITING

United States, Colorado

Regents of the University of Colorado

Aurora, Colorado, United States, 80045

RECRUITING

United States, Colorado

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States, 80218

RECRUITING

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

RECRUITING

United States, Road cancer

Karmanos Cancer Insitute

Detroit, Road cancer, United States, 48201

RECRUITING

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

RECRUITING

United States, New York

Stony Brook University

Stony Brook, New York, United States, 11794

RECRUITING

United States, Tennessee

SCRI Oncology Partners - Nashville

Nashville, Tennessee, United States, 37203

RECRUITING

United States, Virginia

NEXT Oncology Virginia

Fairfax, Virginia, United States, 22031

RECRUITING

United States, Washington

Fred Hutchinson Cancer Center

Seattle, Washington, United States, 98109

RECRUITING

Belgium,

Institute Jules Table

Anderlecht, Belgium, 1070

RECRUITING

Belgium,

UZ Leuven - Campus Gasthuisberg

Leuven, Belgium, 3000

RECRUITING

Belgium,

Gza Hopsitals Campus Sint-Augustine

Wilrijk, Belgium, 2610

RECRUITING

France,

CANCER CANCER CENTER CLCC - Center Georges Francois Leclerc (CGFL)

Dijon, France, 21079

RECRUITING

France,

Oscar Lambret Center

Lille, France, 59020

RECRUITING

France,

Center Leon Berard

Lyon, France, 69008

RECRUITING

France,

Center Antoine Lacassagne

Nice, France, 06189

RECRUITING

France,

Hospital Lyon Sud

Pierre Benite, France, 69310

RECRUITING

France,

Gustave Roussy Institute

Villejuif, France, 94805

RECRUITING

Italy,

San Gerardo-Asst Monza Hospital

Monza, Italy, 20900

RECRUITING

Italy,

Humanitas Clinical Institute

Rozzano, Italy, 20089

RECRUITING

Korea, Republic of,

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 21565

RECRUITING

Korea, Republic of,

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

RECRUITING

Korea, Republic of,

Severance Hospital

Seoul, Korea, Republic of, 03722

RECRUITING

Korea, Republic of,

Asan Medical Center

Seoul, Korea, Republic of, 05505

RECRUITING

Korea, Republic of,

Samsung Medical Center

Seoul, Korea, Republic of, 06351

RECRUITING

Spain,

NEXT Oncology Phase I Unit / IOB- Hospital Quironsalud Barcelona

Barcelona, Spain, 08023

RECRUITING

Spain,

Blessed Maria Ana Hospital

Madrid, Spain, 28007

RECRUITING

Spain,

October 12 University Hospital

Madrid, Spain, 28041

RECRUITING

Spain,

START - Madrid

Madrid, Spain, 28050