Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
OnKure, Inc. (Voir sur ClinicalTrials)
février 2024
août 2027
08 juillet 2026
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Djedjiga Oudni | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - 06189 - Nice - France | Jennifer Oudard | Contact (sur clinicalTrials) | |||
| Centre de Lutte Contre le Cancer CLCC - Centre Georges Francois Leclerc (CGFL) - 21079 - Dijon - France | Peggy Philippe | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - 69008 - Lyon - France | Amelie Vey | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - 59020 - Lille - France | Amelie Decourcelle | Contact (sur clinicalTrials) | |||
Critères
Tous
- 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.