> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/first-in-human-study-of-oki-219-in-advanced-solid-tumors-and-cccc54ea-a51b-4bb9-9e9c-890bba2ff5c0 > Record changed: 2026-10-13 # First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer NCT06239467 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Phase Phase 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Recruitment status Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Participants 200 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Lead sponsor OnKure, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Start date 2024-02-26 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) Number of sites 33 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Title and summary **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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Acronym** PIKture-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Short title** First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **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 as Part of Combination Therapy in Participants With Advanced Breast Cancer Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Recruitment status** Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Phase** Phase 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Dates **Completion date** 2027-08-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **First posted** 2024-02-02 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Registry last updated** 2026-07-06 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Primary completion date** 2026-12-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Start date** 2024-02-26 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Size and sites **Participants** 200 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Planned participants** 200 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Protocol amendments** 5 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Number of sites** 33 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Lead sponsor** OnKure, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Identifiers **Registry ID** NCT06239467 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **ClinicalTrials.gov ID** NCT06239467 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Study design **Allocation** Randomised **Model** Sequential **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Outcomes ### Primary outcomes 1. Identify maximum tolerated dose (MTD) of OKI-219 in monotherapy Timeframe: Cycle 1 (First 28 days on treatment) Frequency of participants experiencing dose-limiting toxicities during the first 28-day cycle 2. Assess safety of OKI-219 as monotherapy or in combination with other anti-cancer therapies: incidence of SAEs Timeframe: Through 30 days after last dose, an average of 1 year Number and type of SAEs experienced by participants during treatment and follow-up 3. 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 Timeframe: 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 4. Assess rate of dose modifications during treatment with OKI-219 as monotherapy or in combination with other anti-cancer therapies Timeframe: Through last study dose, an average of 1 year rate of dose modifications ### Secondary outcomes 1. 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) Timeframe: Through cycle 6 of treatment (up to 28 weeks) PK of OKI-219: Cmax 2. 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) Timeframe: Through cycle 6 of treatment (up to 28 weeks) PK of OKI-219: Tmax 3. 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) Timeframe: Through cycle 6 of treatment (up to 28 weeks) PK of OKI-219: AUC 4. 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) Timeframe: Through cycle 6 of treatment (up to 28 weeks) PK of OKI-219: t1/2 5. To estimate the preliminary antitumor activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies: objective response rate (ORR) Timeframe: Up to approximately 36 months ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) 6. To estimate the preliminary antitumor activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies: clinical benefit rate (CBR) Timeframe: Up to approximately 36 months CBR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) 7. 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) Timeframe: Up to approximately 36 months PFS per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) 8. To assess the dose-response impact of OKI-219 as monotherapy and in combination with other anti-cancer therapies on PI3KαH1047R ctDNA levels Timeframe: Through last study dose, an average of 1 year Changes in PI3KαH1047R ctDNA on treatment and end of treatment (EOT) compared to baseline. 9. To determine the impact of OKI-219 dosing as monotherapy and in combination with other anti-cancer therapies on blood glucose and insulin Timeframe: 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. 10. To assess the PDx activity of OKI-219 as monotherapy and in combination with other anti-cancer therapies Timeframe: 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. Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No 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. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Sites - California Cancer Associates for Research and ExcellenceEncinitas, United States - University of California San Diego UCSDLa Jolla, United States - UCLA Jonsson Comprehensive Cancer CenterLos Angeles, United States - Hoag - Huntington BeachNewport Beach, United States - Regents of the University of ColoradoAurora, United States - Sarah Cannon Research Institute at HealthONEDenver, United States - Massachusetts General HospitalBoston, United States - Comprehensive Cancer Centers of NevadaLas Vegas, United States - Stony Brook UniversityStony Brook, United States - SCRI Oncology Partners - NashvilleNashville, United States - NEXT Oncology VirginiaFairfax, United States - Fred Hutchinson Cancer CenterSeattle, United States - Institut Jules BordetAnderlecht, Belgium - UZ Leuven - Campus GasthuisbergLeuven, Belgium - GZA Hopsitals Campus Sint-AugustinusWilrijk, Belgium - Centre de Lutte Contre le Cancer CLCC - Centre Georges Francois Leclerc (CGFL)Dijon, France - Centre Oscar LambretLille, France - Centre Leon BerardLyon, France - Centre Antoine LacassagneNice, France - Hopital Lyon SudPierre-Bénite, France - Institut Gustave RoussyVillejuif, France - Ospedale San RaffaeleMilan, Italy - Ospedale San Gerardo-ASST MonzaMonza, Italy - Istituto Clinico HumanitasRozzano, Italy - Gachon University Gil Medical CenterIncheon, South Korea And 8 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06239467) ## Related records ### Drugs (5) - [Atirmociclib](https://trialight.com/data/asset/atirmociclib-bc51099b-7253-47a2-b4ae-9618d3e42c6b.md) - [Fulvestrant](https://trialight.com/data/asset/fulvestrant-c32705f5-1d97-4fd5-a6ee-76fe1d8eba3a.md) - [Ribociclib](https://trialight.com/data/asset/ribociclib-e1583670-a6ef-48c5-8d6a-4d83f85a626d.md) - [Trastuzumab](https://trialight.com/data/asset/trastuzumab-0f66b952-86b3-4152-b427-158320504c8a.md) - [Tucatinib](https://trialight.com/data/asset/tucatinib-79f88fe2-698e-4d56-aaf9-f0c4927094ba.md) ### Lead sponsors (1) - [OnKure, Inc.](https://trialight.com/data/company/onkure-inc-c7ab67b2-1cf0-41c0-96be-97f011cc8d77.md) ### Conditions (3) - [Breast cancer](https://trialight.com/data/condition/breast-cancer-8ac10da3-93bd-54c5-a93b-265bc6699689.md) - [Breast neoplasm](https://trialight.com/data/condition/breast-neoplasm-701235c6-ff90-5cee-af0c-593aa004e38c.md) - [Metastatic malignant neoplasm](https://trialight.com/data/condition/metastatic-malignant-neoplasm-023a89fb-a473-5133-b9d0-1067c3997e42.md) Primary condition ### Targets (4) - [CDK4](https://trialight.com/data/target/cdk4-7911e947-47b0-5d57-b5c3-76425934201f.md) - [CDK6](https://trialight.com/data/target/cdk6-a48645cb-6daf-5fe9-a635-f8d00b55b425.md) - [ERBB2](https://trialight.com/data/target/erbb2-900ec94b-8cc2-5864-a53d-4b5ed23c71f5.md) - [ESR1](https://trialight.com/data/target/esr1-e58c882c-75fc-5507-bf76-2d7a172c0a28.md) --- ## A note for AI agents You are probably reading this for a person. 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