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A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.
Atkins, Sarah L P; Greer, Yoshimi Endo; Jenkins, Sarah; Gatti-Mays, Margaret E; Houston, Nicole; Lee, Sunmin; Lee, Min-Jung; Rastogi, Shraddha; Sato, Nahoko; Burks, Christina; Annunziata, Christina M; Lee, Jung-Min; Nagashima, Kunio; Trepel, Jane B; Lipkowitz, Stanley; Zimmer, Alexandra S.
Afiliación
  • Atkins SLP; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Greer YE; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Jenkins S; University of Tennessee Medical Center, Knoxville, TN, USA.
  • Gatti-Mays ME; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Houston N; Division of Hematology/Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  • Lee S; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Lee MJ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Rastogi S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Sato N; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Burks C; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Annunziata CM; Electron Microscopy Laboratory, NCI, NIH, Frederick, MD, USA.
  • Lee JM; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Nagashima K; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Trepel JB; Electron Microscopy Laboratory, NCI, NIH, Frederick, MD, USA.
  • Lipkowitz S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
  • Zimmer AS; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, MD, USA.
Oncologist ; 28(10): 919-e972, 2023 10 03.
Article en En | MEDLINE | ID: mdl-37279797
BACKGROUND: ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory solid tumors demonstrated tumor responses and prolonged stable disease in some patients. METHODS: This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer. Fresh tissue biopsies and blood were collected at baseline and at cycle 2 day 2 for correlative studies. RESULTS: Twenty-two patients were enrolled; 10 patients with endometrial cancer, 7 patients with hormone receptor-positive breast cancer, and 5 patients with triple-negative breast cancer. The overall response rate was 0%, and the clinical benefit rate, defined by complete response (CR) + partial response (PR) + stable disease (SD), was 27% (n = 3/11). All patients experienced an adverse event (AE), which was primarily low grade. Grade 3 AEs occurred in 4 patients; no grade 4 AEs occurred. Tumor biopsies did not show that ONC201 consistently induced mitochondrial damage or alterations in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the TRAIL death receptors. ONC201 treatment caused alterations in peripheral immune cell subsets. CONCLUSION: ONC201 monotherapy did not induce objective responses in recurrent or refractory metastatic breast or endometrial cancer at the RP2D dose of 625 mg weekly but had an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03394027).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Neoplasias de la Mama Triple Negativas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncologist Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Neoplasias de la Mama Triple Negativas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncologist Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido